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Ko HY, Bea S, Yoon D, Hong B, Bae JH, Cho YM, Shin JY. Incretin-based drugs and the risk of gallbladder or biliary tract diseases among patients with type 2 diabetes across categories of body mass index: a nationwide cohort study. THE LANCET REGIONAL HEALTH. WESTERN PACIFIC 2025; 56:101242. [PMID: 40226782 PMCID: PMC11992583 DOI: 10.1016/j.lanwpc.2024.101242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 10/06/2024] [Accepted: 10/31/2024] [Indexed: 04/15/2025]
Abstract
Background Despite emerging evidence of gallbladder or biliary tract diseases (GBD) risk regarding incretin-based drugs, population-specific safety profile considering obesity is lacking. We aimed to assess whether stratification by body mass index (BMI) modifies the measures of association between incretin-based drugs and the risk of GBD. Methods We conducted an active-comparator, new-user cohort study using a nationwide claims data (2013-2022) of Korea. We included type 2 diabetes (T2D) patients stratified by Asian BMI categories: Normal, 18.5 to <23 kg/m2; Overweight, 23 to <25 kg/m2; Obese, ≥25 kg/m2. The primary outcome was a composite of GBD, including cholelithiasis, cholecystitis, obstruction of the gallbladder or bile duct, cholangitis, and cholecystectomy. We used 1:1 propensity score (PS) matching and estimated hazard ratios (HR) with 95% confidence intervals (CI) using Cox models. Findings New users of DPP4i and SGLT2i were 1:1 PS matched (n = 251,420 pairs; 186,697 obese, 39,974 overweight, and 24,749 normal weight pairs). The overall HR for the risk of GBD with DPP4i vs. SGLT2i was 1.21 (95% CI 1.14-1.28), with no effect modification by BMI (p-value: 0.83). For the second cohort, new users of GLP1RA and SGLT2i were 1:1 PS matched (n = 45,443 pairs; 28,011 obese, 8948 overweight, and 8484 normal weight pairs). The overall HR for the risk of GBD with GLP1RA vs. SGLT2i was 1.27 (1.07-1.50), with no effect modification by BMI (p-value: 0.73). Interpretation The increased risks of GBD were presented in both cohorts with no evidence of effect heterogeneity by BMI. Funding Ministry of Food and Drug Safety, Health Fellowship Foundation.
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Affiliation(s)
- Hwa Yeon Ko
- School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea
| | - Sungho Bea
- School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Dongwon Yoon
- School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon-si, South Korea
| | - Bin Hong
- School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea
| | - Jae Hyun Bae
- Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Young Min Cho
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
| | - Ju-Young Shin
- School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon-si, South Korea
- Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea
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Yang S, Song J, Yang Z, Li N, Wu J, Hou S. Association between Atherogenic index of plasma and gallstones in the United States adults: A cross-sectional analysis of NHANES 2017-2020. Prev Med Rep 2025; 50:102972. [PMID: 39897733 PMCID: PMC11783124 DOI: 10.1016/j.pmedr.2025.102972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 01/10/2025] [Accepted: 01/10/2025] [Indexed: 02/04/2025] Open
Abstract
Background Although substantial evidence suggests an association between dyslipidemia as an isolated factor and gallstones, research on the Atherogenic Index of Plasma (AIP) and gallstones remains limited. Methods A total of 3557 eligible adults from the United States were selected for cross-sectional analysis using the 2017-2020 National Health and Nutrition Examination Survey database. Logistic regression was employed to evaluate the association between AIP gallstones. Restricted cubic spline (RCS) analysis and threshold effect analysis were conducted to explore potential non-linear relationship. Results The study found a positive association between higher AIP levels and higher odds of gallstones. In the fully adjusted logistic regression model, each 1-unit increase in AIP was associated with 59 % higher odds of gallstones (OR = 1.59, 95 % CI: 1.06, 2.38). Compared to the lowest quartile of AIP, the highest quartile showed 82 % higher odds of gallstones (OR = 1.82, 95 % CI: 1.23, 2.69). RCS analysis revealed a non-linear relationship between AIP and gallstones, with threshold effect analysis identifying a turning point at -0.13, where AIP had a positive correlation with gallstones before this threshold. Conclusion Higher AIP is positively correlated with higher odds of gallstones, showing a non-linear relationship. As AIP increases, the odds of gallstones also rise, but this relationship is no longer observed beyond a certain threshold. It is recommended to maintain appropriate AIP levels to reduce the incidence of gallstones.
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Affiliation(s)
- Shuang Yang
- Department of Operating room, Fuyang Normal University Affiliated Second Hospital, Fuyang 236000, Anhui, China
| | - Jianhui Song
- Department of General Surgery, Affiliated Xinhua Hospital of Dalian University, Dalian 116001, Liaoning, China
| | - Zhengbo Yang
- Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning, China
| | - Nanbo Li
- Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning, China
| | - Ju Wu
- Department of General Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning, China
| | - Shuangshuang Hou
- Department of Graduate School, Dalian Medical University, Dalian 116000, Liaoning, China
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Gameil MA, Yousef EAAM, Marzouk RE, Emara MH, Abdelkader AH, Salama RI. The relative risk of clinically relevant cholelithiasis among glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus, real-world study. Diabetol Metab Syndr 2024; 16:293. [PMID: 39633496 PMCID: PMC11616335 DOI: 10.1186/s13098-024-01526-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Accepted: 11/13/2024] [Indexed: 12/07/2024] Open
Abstract
BACKGROUND AND AIM The association between biliary disorders with weight reduction enhanced by GLP-1RAs was observed frequently, nevertheless, the relative risk of the clinically relevant cholelithiasis was not specified clearly among different GLP-1RAs. METHODS 308 patients with type 2 diabetes mellitus (T2D) were recruited and divided into 4 groups; liraglutide, dulaglutide, semaglutide, versus control group; comprised of 69, 76, 71, and 92, respectively. Clinical history, examination, laboratory, and radiology tests were implemented. RESULTS Cholelithiasis significantly associates GLP1-RAs (p = 0.033). Overall cholelithiasis was evident in 31.2% of our participants. Symptomatic cholelithiasis prevails in 60.4% of patients with cholelithiasis. Symptomatic complicated cholelithiasis prevailed in 33.3%; distributed in 28.1%, 28.1%, 21.9%, and 21.9% in liraglutide, semaglutide, dulaglutide, and control groups, respectively. Meanwhile, symptomatic uncomplicated cholelithiasis was observed in 27.1%; distributed in 34.6%, 30.8%, 15.4%, and 19.2% in Liraglutide, semaglutide, dulaglutide, and control groups, respectively. Asymptomatic cholelithiasis was noted in 36.8%, 21.1%, 10.5%, and 31.6% of patients with dulaglutide, semaglutide, liraglutide, and control groups, respectively. Specifically, 81.1%, 68%, and 44% of patients with liraglutide, semaglutide, and dulaglutide experienced symptomatic cholelithiasis. The relative risk of cholelithiasis was 1.2, 1.3, and 1.4 in liraglutide, dulaglutide, and semaglutide with number needed to harm of 17.25, 14.69, and 10.96, respectively. The relative risk of symptomatic cholelithiasis was 1.6, 0.9, and 1.4 in liraglutide, dulaglutide, and semaglutide with number needed to harm of 3.14, 16.67, and 5.56, respectively. CONCLUSION Liraglutide was associated with the highest risk of clinically relevant cholelithiasis than semaglutide, and dulaglutide in patients with T2D.
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Affiliation(s)
- Mohammed Ali Gameil
- Endocrinology Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Dakahlia, Egypt.
| | | | - Rehab Elsayed Marzouk
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Helwan University, Helwan, Cairo, Egypt
| | - Mohamed H Emara
- Hepatology, Gastroenterology, Infectious Diseases Department, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt
- Department of Internal Medicine, Alyousif Hospital, Alkhobar, Kingdom of Saudi Arabia
| | - Abeer H Abdelkader
- Tropical Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Alsharqia, Egypt
| | - Rasha Ibrahim Salama
- Tropical Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Alsharqia, Egypt
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Wang ZQ, Zhang JY, Tang X, Zhou JB. Hypoglycemic drugs, circulating inflammatory proteins, and gallbladder diseases: A mediation mendelian randomization study. Diabetes Res Clin Pract 2024; 217:111882. [PMID: 39366640 DOI: 10.1016/j.diabres.2024.111882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 08/31/2024] [Accepted: 10/01/2024] [Indexed: 10/06/2024]
Abstract
BACKGROUND The relationship of hypoglycemic drugs, inflammatory proteins and gallbladder diseases remain unknown. METHODS Four hypoglycemic drugs were selected as exposure: glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and metformin. The outcome were two gallbladder diseases: cholecystitis and cholelithiasis. Mendelian Randomization (MR) was employed to determine the association between hypoglycemic drugs and gallbladder diseases. RESULTS DPP-4i and SGLT-2i had no effect on cholecystitis and cholelithiasis. However, a causal relationship was found between inhibition of ETFDH gene, a target of metformin expressed in cultured fibroblasts, and cholelithiasis (OR: 0.84, 95 %CI: (0.72,0.97), p = 0.021), as well as between GLP1R expression in the brain caudate basal ganglia and cholecystitis (OR: 1.29, 95 %CI: (1.11,1.49), p = 0.001). The effect of ETFDH inhibition on cholelithiasis through Interleukin-10 receptor subunit beta (IL-10RB) levels and Neurotrophin-3 (NT-3) levels, with a mediated proportion of 8 % and 8 %, respectively. CONCLUSION Metformin plays a protective role in cholelithiasis, while GLP-1RA have a harmful effect on the risk of cholecystitis. Metformin may reduce the risk of cholelithiasis by modulating the levels of Neurotrophin-3 (NT-3) and Interleukin-10 receptor subunit beta (IL-10RB). Further clinical and mechanistic studies are required to confirm these findings.
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Affiliation(s)
- Zi-Qi Wang
- Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Jin-Yan Zhang
- Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | | | - Jian-Bo Zhou
- Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
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Drucker DJ. Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity. Diabetes Care 2024; 47:1873-1888. [PMID: 38843460 DOI: 10.2337/dci24-0003] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 04/14/2024] [Indexed: 10/23/2024]
Abstract
The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits of GLP-1RA in select patient populations. In ongoing trials investigators are interrogating the efficacy of these agents for new indications, including metabolic liver disease, peripheral artery disease, Parkinson disease, and Alzheimer disease. The success of GLP-1-based medicines has spurred the development of new molecular entities and combinations with unique pharmacokinetic and pharmacodynamic profiles, exemplified by tirzepatide, a GIP-GLP-1 receptor coagonist. Simultaneously, investigational molecules such as maritide block the GIP and activate the GLP-1 receptor, whereas retatrutide and survodutide enable simultaneous activation of the glucagon and GLP-1 receptors. Here I highlight evidence establishing the efficacy of GLP-1-based medicines, while discussing data that inform safety, focusing on muscle strength, bone density and fractures, exercise capacity, gastrointestinal motility, retained gastric contents and anesthesia, pancreatic and biliary tract disorders, and the risk of cancer. Rapid progress in development of highly efficacious GLP-1 medicines, and anticipated differentiation of newer agents in subsets of metabolic disorders, will provide greater opportunities for use of personalized medicine approaches to improve the health of people living with cardiometabolic disorders.
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Affiliation(s)
- Daniel J Drucker
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada
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Janez A, Muzurovic E, Bogdanski P, Czupryniak L, Fabryova L, Fras Z, Guja C, Haluzik M, Kempler P, Lalic N, Mullerova D, Stoian AP, Papanas N, Rahelic D, Silva-Nunes J, Tankova T, Yumuk V, Rizzo M. Modern Management of Cardiometabolic Continuum: From Overweight/Obesity to Prediabetes/Type 2 Diabetes Mellitus. Recommendations from the Eastern and Southern Europe Diabetes and Obesity Expert Group. Diabetes Ther 2024; 15:1865-1892. [PMID: 38990471 PMCID: PMC11330437 DOI: 10.1007/s13300-024-01615-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 06/20/2024] [Indexed: 07/12/2024] Open
Abstract
The increasing global incidence of obesity and type 2 diabetes mellitus (T2D) underscores the urgency of addressing these interconnected health challenges. Obesity enhances genetic and environmental influences on T2D, being not only a primary risk factor but also exacerbating its severity. The complex mechanisms linking obesity and T2D involve adiposity-driven changes in β-cell function, adipose tissue functioning, and multi-organ insulin resistance (IR). Early detection and tailored treatment of T2D and obesity are crucial to mitigate future complications. Moreover, personalized and early intensified therapy considering the presence of comorbidities can delay disease progression and diminish the risk of cardiorenal complications. Employing combination therapies and embracing a disease-modifying strategy are paramount. Clinical trials provide evidence confirming the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1 RAs). Their use is associated with substantial and durable body weight reduction, exceeding 15%, and improved glucose control which further translate into T2D prevention, possible disease remission, and improvement of cardiometabolic risk factors and associated complications. Therefore, on the basis of clinical experience and current evidence, the Eastern and Southern Europe Diabetes and Obesity Expert Group recommends a personalized, polymodal approach (comprising GLP-1 RAs) tailored to individual patient's disease phenotype to optimize diabetes and obesity therapy. We also expect that the increasing availability of dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists will significantly contribute to the modern management of the cardiometabolic continuum.
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Affiliation(s)
- Andrej Janez
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia.
| | - Emir Muzurovic
- Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro
| | - Pawel Bogdanski
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, University of Medical Sciences, Poznan, Poland
| | - Leszek Czupryniak
- Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warszawa, Poland
| | - Lubomira Fabryova
- MetabolKLINIK sro, Department for Diabetes and Metabolic Disorders, Lipid Clinic, MED PED Centre, Biomedical Research Centre of Slovak Academy of Sciences, Slovak Health University, Bratislava, Slovak Republic
| | - Zlatko Fras
- Preventive Cardiology Unit, Division of Medicine, University Medical Centre Ljubljana and Chair of Internal Medicine, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia
| | - Cristian Guja
- Clinic of Diabetes, Nutrition and Metabolic Diseases, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Martin Haluzik
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Vídeňská 1958/9, 140 21, Prague 4, Czech Republic
| | - Peter Kempler
- Department of Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Nebojsa Lalic
- Faculty of Medicine, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, University of Belgrade, Belgrade, Serbia
| | - Dana Mullerova
- Faculty of Medicine in Pilsen, Department of Public Health and Preventive Medicine and Faculty Hospital in Pilsen, 1st Internal Clinic, Charles University, Pilsen, Czech Republic
| | - Anca Pantea Stoian
- Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Nikolaos Papanas
- Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dario Rahelic
- Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia
- Catholic University of Croatia School of Medicine, Zagreb, Croatia
- Josip Juraj Strossmayer, University of Osijek School of Medicine, Osijek, Croatia
| | - José Silva-Nunes
- NOVA Medical School, New University of Lisbon, Lisbon, Portugal
- Department of Endocrinology, Diabetes and Metabolism, Unidade Local de Saúde São José, Lisbon, Portugal
| | - Tsvetalina Tankova
- Department of Endocrinology, Faculty of Medicine, Medical University, Sofia, Bulgaria
| | - Volkan Yumuk
- Division of Endocrinology, Metabolism and Diabetes, Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty, Istanbul, Turkey
| | - Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), School of Medicine, University of Palermo, Palermo, Italy
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Shapiro SB, Yin H, Yu OHY, Azoulay L. Dipeptidyl Peptidase-4 Inhibitors and the Risk of Gallbladder and Bile Duct Disease Among Patients with Type 2 Diabetes: A Population-Based Cohort Study. Drug Saf 2024; 47:759-769. [PMID: 38720114 DOI: 10.1007/s40264-024-01434-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/15/2024] [Indexed: 07/30/2024]
Abstract
INTRODUCTION The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with an increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. METHODS We conducted a population-based cohort study using an active comparator, new-user design. We used data from the United Kingdom Clinical Practice Research Datalink to identify patients newly treated with either a DPP-4 inhibitor or sodium-glucose cotransporter-2 (SGLT-2) inhibitor between January 2013 and December 2020. We fitted Cox proportional hazards models with propensity score fine stratification weighting to estimate the hazard ratio (HR) and its 95% confidence interval (CI) for incident gallbladder and bile duct disease associated with DPP-4 inhibitors compared to SGLT-2 inhibitors. RESULTS DPP-4 inhibitors were associated with a 46% increased risk of gallbladder and bile duct disease (4.3 vs. 3.0 events per 1000 person-years, HR 1.46, 95% CI 1.17-1.83). At 6 months and 1 year, 745 and 948 patients, respectively, would need to be treated with DPP-4 inhibitors for one patient to experience a gallbladder or bile duct disease. CONCLUSIONS In this population-based cohort study, the use of DPP-4 inhibitors, when compared with SGLT-2 inhibitors, was associated with a moderately increased risk of gallbladder and bile duct disease among patients with type 2 diabetes. This outcome was still quite rare with a high number needed to harm at 6 months and 1 year.
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Affiliation(s)
- Samantha B Shapiro
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, H425.1, Montreal, H3T 1E2, Canada
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, H3A 1G1, Canada
| | - Hui Yin
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, H425.1, Montreal, H3T 1E2, Canada
| | - Oriana H Y Yu
- Division of Endocrinology, Jewish General Hospital, Montreal, H3T 1E2, Canada
| | - Laurent Azoulay
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Cote Sainte-Catherine, H425.1, Montreal, H3T 1E2, Canada.
- Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, H3A 1G1, Canada.
- Gerald Bronfman Department of Oncology, McGill University, Montreal, H4A 3T2, Canada.
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Komargodski R, Wittenberg A, Bahat H, Rachmiel M. Acute Kidney and Liver Injury Associated With Low-Dose Liraglutide in an Obese Adolescent Patient. Pediatrics 2024; 154:e2023063719. [PMID: 38864114 DOI: 10.1542/peds.2023-063719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 03/14/2024] [Accepted: 03/29/2024] [Indexed: 06/13/2024] Open
Abstract
In 2020, the US Food and Drug Administration approved liraglutide (glucagon-like-peptide-1-receptor-agonist) as an adjunctive therapy for weight management in adolescents aged 12 to 18 years in combination with a reduced-calorie diet and increased physical activity. The 2023 American Academy of Pediatrics guidelines recommend pharmacotherapy with glucagon-like-peptide-1-receptor-agonist as a second-line therapy in obesity management. Although reports in adults have suggested a link between liraglutide and adverse effects including hepatic injury and acute kidney injury (AKI), these effects have not previously been reported among adolescents treated with liraglutide for weight loss. We present a 17-year-old male who developed AKI and evidence of hepatic injury (significant elevation of hepatic transaminases) after 3 months administration of the lowest dosage of liraglutide (0.6 mg/day) for management of class III obesity. The patient experienced significant loss of appetite, weight loss, and melancholy during the treatment period. One month after discontinuing liraglutide, his mood had improved, his liver enzymes had returned to normal, and AKI had resolved. The Adverse Drug Reaction Probability Scale suggested a high likelihood of a causative association between liraglutide and his symptoms. Our report highlights the importance of vigilance in monitoring for these potential adverse effects among adolescents treated for obesity with any dose of liraglutide.
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Affiliation(s)
- Rinat Komargodski
- Pharmacy Services, Shamir (Assaf Harofeh) Medical Center, Beer Ya'akov, Israel
- School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Avigail Wittenberg
- Pediatric Endocrinology and Diabetes Institute, Shamir (Assaf Harofeh) Medical Center, Beer Ya'akov, Israel
| | - Hilla Bahat
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Nephrology Unit, Shamir (Assaf Harofeh) Medical Center, Beer Ya'akov, Israel
| | - Marianna Rachmiel
- Pediatric Endocrinology and Diabetes Institute, Shamir (Assaf Harofeh) Medical Center, Beer Ya'akov, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Sarzani R, Landolfo M, Di Pentima C, Ortensi B, Falcioni P, Sabbatini L, Massacesi A, Rampino I, Spannella F, Giulietti F. Adipocentric origin of the common cardiometabolic complications of obesity in the young up to the very old: pathophysiology and new therapeutic opportunities. Front Med (Lausanne) 2024; 11:1365183. [PMID: 38654832 PMCID: PMC11037084 DOI: 10.3389/fmed.2024.1365183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Accepted: 03/26/2024] [Indexed: 04/26/2024] Open
Abstract
Obesity is a multifactorial chronic disease characterized by an excess of adipose tissue, affecting people of all ages. In the last 40 years, the incidence of overweight and obesity almost tripled worldwide. The accumulation of "visceral" adipose tissue increases with aging, leading to several cardio-metabolic consequences: from increased blood pressure to overt arterial hypertension, from insulin-resistance to overt type 2 diabetes mellitus (T2DM), dyslipidemia, chronic kidney disease (CKD), and obstructive sleep apnea. The increasing use of innovative drugs, namely glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2-i), is changing the management of obesity and its related cardiovascular complications significantly. These drugs, first considered only for T2DM treatment, are now used in overweight patients with visceral adiposity or obese patients, as obesity is no longer just a risk factor but a critical condition at the basis of common metabolic, cardiovascular, and renal diseases. An adipocentric vision and approach should become the cornerstone of visceral overweight and obesity integrated management and treatment, reducing and avoiding the onset of obesity-related multiple risk factors and their clinical complications. According to recent progress in basic and clinical research on adiposity, this narrative review aims to contribute to a novel clinical approach focusing on pathophysiological and therapeutic insights.
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Affiliation(s)
- Riccardo Sarzani
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
- Centre for Obesity, Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy
| | - Matteo Landolfo
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
- Centre for Obesity, Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy
| | - Chiara Di Pentima
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
| | - Beatrice Ortensi
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
- Centre for Obesity, Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy
| | - Paolo Falcioni
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
- Centre for Obesity, Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy
| | - Lucia Sabbatini
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
- Centre for Obesity, Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy
| | - Adriano Massacesi
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
- Centre for Obesity, Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy
| | - Ilaria Rampino
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
- Centre for Obesity, Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy
| | - Francesco Spannella
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
- Centre for Obesity, Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy
| | - Federico Giulietti
- Internal Medicine and Geriatrics, European Society of Hypertension (ESH) “Hypertension Excellence Centre”, Società Italiana per lo Studio dell'Aterosclerosi (SISA) LIPIGEN Centre, IRCCS INRCA, Ancona, Italy
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10
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Chan PYW, Mika AP, Martin JR, Wilson JM. Glucagon-like Peptide-1 Agonists: What the Orthopaedic Surgeon Needs to Know. JBJS Rev 2024; 12:01874474-202401000-00003. [PMID: 38181103 DOI: 10.2106/jbjs.rvw.23.00167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2024]
Abstract
» Orthopaedic surgeons are increasingly likely to encounter patients with obesity and/or type 2 diabetes taking glucagon-like peptide-1 (GLP-1) agonists for weight loss.» GLP-1 agonists are an effective treatment for weight loss with semaglutide and tirzepatide being the most effective agents. Randomized controlled trials using these agents have reported weight loss up to 21 kg (46 lb).» The use of GLP-1 agonists preoperatively can improve glycemic control, which can potentially reduce the risk of postoperative complications. However, multiple cases of intraoperative aspiration/regurgitation have been reported, potentially related to the effect of GLP-1 agonists on gastric emptying.» While efficacious, GLP-1 agonists may not produce sufficient weight loss to achieve body mass index cutoffs for total joint arthroplasty depending on individual patient factors, including starting bodyweight. Multifactorial approaches to weight loss with focus on lifestyle modification in addition to GLP-1 agonists should be considered in such patients.» Although GLP-1 agonists are efficacious agents for weight loss, they may not be accessible or affordable for all patients. Each patient's unique circumstances should be considered when creating an ideal weight loss plan during optimization efforts.
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Affiliation(s)
- Peter Y W Chan
- Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, Tennessee
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11
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Li ZZ, Guan LJ, Ouyang R, Chen ZX, Ouyang GQ, Jiang HX. Global, regional, and national burden of gallbladder and biliary diseases from 1990 to 2019. World J Gastrointest Surg 2023; 15:2564-2578. [PMID: 38111771 PMCID: PMC10725539 DOI: 10.4240/wjgs.v15.i11.2564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 08/02/2023] [Accepted: 08/17/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Gallbladder and biliary diseases (GABDs) are a major public health issue. AIM To analysis the cause-specific incidence, prevalence, and years lived with disability (YLDs) and its temporal trends of GABDs at the global, regional, and national level. Data on GABD were available from the Global Burden of Disease study 2019. METHODS The estimated annual percentage change (EAPC) was used to quantify temporal trend in GABD age-standardized incidence rates (ASIRs), age-standardized prevalence rate (ASPR), and age-standardized YLD rate (ASYR) by region, sex. We analyzed the relationship between the GABD burden and country development level using the human development index (HDI). RESULTS In 2019, the incident cases of GABD were 52003772, with an ASIR of 63432/100000 population. Globally, the number of incident cases and ASIR of GABD increased 97% and 58.9% between 1990 and 2019. Although, the ASPR and ASYR decreased from 1990 to 2019, the number of prevalent and YLDs cases increased. The highest ASIR was observed in Italy, and the highest ASPR and ASYR was observed in United Kingdom. The highest burden of GABD was found in low-SDI region, and the burden in female was significantly higher than males. A generally negative correlation (ρ = -0.24, P < 0.05) of GABD with the EAPC and human development index (HDI) (in 2021) were observed for ASIR. What's more, no correlation in ASPR (ρ = -0.06, P = 0.39) and ASYR (ρ = -0.07, P = 0.36) of GABD with the EAPC and HDI (in 2021) were observed, respectively. CONCLUSION GABD remain a major global public health challenge; however, the burden of GABD varies geographically. Globally, the number of incident cases and ASIR of GABD increased between 1990 and 2019. The results of our study provide insight into the global disease burden of GABD and may assist policymakers in formulating effective policies to mitigate modifiable risk factors.
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Affiliation(s)
- Zhong-Zhuan Li
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
- Department of Gastroenterology, Liuzhou Workers’ Hospital (The Fourth Affiliated Hospital of Guangxi Medical University), Liuzhou 545007, Guangxi Zhuang Autonomous Region, China
| | - Lin-Jing Guan
- Department of Abdomen Ultrasound, Nanning Sixth People’s Hospital, Nanning 530002, Guangxi Zhuang Autonomous Region, China
| | - Rong Ouyang
- Department of Gastroenterology, Liuzhou Workers’ Hospital (The Fourth Affiliated Hospital of Guangxi Medical University), Liuzhou 545007, Guangxi Zhuang Autonomous Region, China
| | - Zhi-Xin Chen
- Department of Gastroenterology, Liuzhou Workers’ Hospital (The Fourth Affiliated Hospital of Guangxi Medical University), Liuzhou 545007, Guangxi Zhuang Autonomous Region, China
| | - Guo-Qing Ouyang
- Department of General Surgery, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou 545006, Guangxi Zhuang Autonomous Region, China
| | - Hai-Xing Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
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12
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Xu Z, Liu Z, Wang Y, Xue J, Chang T, Cui Y, Cheng Y, Liu G, Wang W, Zhou Y, Yu S, Ren Q, Yang W, Qu X, Chen J, Chen X, Deng Q, Yang H, Wang X. Comparing the bioequivalence and safety of liraglutide in healthy Chinese subjects: an open, single-dose, randomized, repeated, two-sequence, two-cycle phase I clinical trial. Expert Rev Clin Pharmacol 2023; 16:363-370. [PMID: 36883362 DOI: 10.1080/17512433.2023.2188192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Abstract
BACKGROUND Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone. Liraglutide, a GLP-1 receptor agonist, can lower blood sugar by increasing insulin production and inhibiting the production of glucagon. This study researched the bioequivalence and safety of the test and reference drugs in healthy Chinese subjects. RESEARCH DESIGN AND METHODS Subjects (N = 28) were randomly divided into group A and group B at a ratio of 1:1 for a two-cycle cross-over study. There was single dose per cycle with subcutaneous injection of the test and reference drugs, respectively. The washout was set at 14 days. Plasma drug concentrations were detected by specific liquid chromatography and tandem mass spectrometry (LC-MS/MS) assays. Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial. RESULTS The geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ for the test and reference drugs were 107.11%, 106.56%, 106.09%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both had good safety in this study. CONCLUSION The study shows that the two drugs had similar bioequivalence and safety. CLINICAL TRIAL REGISTRATION DCTR: CTR20190914; ClinicalTrials.gov: NCT05029076.
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Affiliation(s)
- Zhongnan Xu
- Department of Clinical Research Center, Chia Tai Tianqing Pharmaceutical Group Co.,Ltd, Jiangsu, China
| | - Zhengzhi Liu
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Yanli Wang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Jinling Xue
- Department of Clinical Research Center, Chia Tai Tianqing Pharmaceutical Group Co.,Ltd, Jiangsu, China
| | - Tianying Chang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Yingzi Cui
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Yang Cheng
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Guangwen Liu
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Wanhua Wang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Yannan Zhou
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Shuang Yu
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Qing Ren
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Wei Yang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Xinyao Qu
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Jiahui Chen
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Xuesong Chen
- Quality Control Room of Clinical Trial, Ansiterui Medical Technology Consulting Co., Ltd, Jilin, China
| | - Qiaohuan Deng
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Haimiao Yang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
| | - Xiuge Wang
- Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China
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13
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Nerild HH, Brønden A, Gether IM, Hellmann PH, Baekdal M, Gillum MP, Svenningsen JS, Hartmann B, Rathor N, Kudiyanur Muniraju HA, Rehfeld JF, Holst JJ, Vilsbøll T, Sonne DP, Knop FK. Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility. Diabetes Obes Metab 2023; 25:1632-1637. [PMID: 36781820 DOI: 10.1111/dom.15017] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 02/03/2023] [Accepted: 02/07/2023] [Indexed: 02/15/2023]
Abstract
AIM Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment. MATERIALS AND METHODS In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4 kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6 mg to 3.0 mg once-daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP-2. RESULTS Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0-240 min 24.8 vs. 48.0 min × ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC0-240 min 33.7 vs. 48.5 ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC0-240 min 3650 vs. 4894 min × pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC0-240 min 3760 vs. 4882 min × pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC0-240 min 762 vs. 670 min × pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC0-240 min 873 vs. 628 min × pmol/L; TR 1.39 (1.12; 1.73)]. CONCLUSION Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP-2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide.
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Affiliation(s)
- Henriette H Nerild
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Andreas Brønden
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Ida M Gether
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Pernille H Hellmann
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Mille Baekdal
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
| | - Matthew P Gillum
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens S Svenningsen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Bolette Hartmann
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Jens F Rehfeld
- Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Jens J Holst
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Tina Vilsbøll
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - David P Sonne
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Filip K Knop
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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14
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Bergmann NC, Davies MJ, Lingvay I, Knop FK. Semaglutide for the treatment of overweight and obesity: A review. Diabetes Obes Metab 2023; 25:18-35. [PMID: 36254579 PMCID: PMC10092086 DOI: 10.1111/dom.14863] [Citation(s) in RCA: 80] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 09/01/2022] [Accepted: 09/04/2022] [Indexed: 12/14/2022]
Abstract
Obesity is a chronic, relapsing disease associated with multiple complications and a substantial morbidity, mortality and health care burden. Pharmacological treatments for obesity provide a valuable adjunct to lifestyle intervention, which often achieves only limited weight loss that is difficult to maintain. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once-weekly subcutaneous semaglutide 2.4 mg (a glucagon-like peptide-1 analogue) in people with overweight or obesity. Across STEP 1, 3, 4 and 8, semaglutide 2.4 mg was associated with mean weight losses of 14.9%-17.4% in individuals with overweight or obesity without type 2 diabetes from baseline to week 68; 69%-79% of participants achieved ≥10% weight loss with semaglutide 2.4 mg (vs. 12%-27% with placebo) and 51%-64% achieved ≥15% weight loss (vs. 5%-13% with placebo). In STEP 5, mean weight loss was -15.2% with semaglutide 2.4 mg versus -2.6% with placebo from baseline to week 104. In STEP 2 (individuals with overweight or obesity, and type 2 diabetes), mean weight loss was -9.6% with semaglutide 2.4 mg versus -3.4% with placebo from baseline to week 68. Improvements in cardiometabolic risk factors, including high blood pressure, atherogenic lipids and benefits on physical function and quality of life were seen with semaglutide 2.4 mg. The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events. The magnitude of weight loss reported in the STEP trials offers the potential for clinically relevant improvement for individuals with obesity-related diseases.
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Affiliation(s)
| | - Melanie J. Davies
- Diabetes Research CentreUniversity of LeicesterLeicesterUK
- NIHR Leicester Biomedical Research CentreLeicesterUK
| | - Ildiko Lingvay
- Department of Internal Medicine/Endocrinology and Department of Population and Data SciencesUniversity of Texas Southwestern Medical CenterDallasTexasUSA
| | - Filip K. Knop
- Steno Diabetes Center CopenhagenHerlevDenmark
- Department of Clinical Medicine, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark
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15
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Kårhus ML, Knop FK. Liraglutide versus colesevelam for treating bile acid diarrhoea - Authors' reply. Lancet Gastroenterol Hepatol 2022; 7:1075-1076. [PMID: 36370738 DOI: 10.1016/s2468-1253(22)00344-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 10/03/2022] [Indexed: 06/16/2023]
Affiliation(s)
- Martin L Kårhus
- Center for Clinical Metabolic Research, Copenhagen University Hospital Herlev and Gentofte, DK-2900 Hellerup, Denmark
| | - Filip K Knop
- Center for Clinical Metabolic Research, Copenhagen University Hospital Herlev and Gentofte, DK-2900 Hellerup, Denmark; Department of Clinical Medicine and Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark.
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16
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Zhang F, Ge C. Liraglutide versus colesevelam for treating bile acid diarrhoea. Lancet Gastroenterol Hepatol 2022; 7:1075. [PMID: 36370737 DOI: 10.1016/s2468-1253(22)00304-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Accepted: 09/07/2022] [Indexed: 06/16/2023]
Affiliation(s)
- Fei Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Hunnan Division of The First Hospital of China Medical University, Shenyang, 11001, China.
| | - Chunlin Ge
- Department of Hepatobiliary and Pancreatic Surgery, Hunnan Division of The First Hospital of China Medical University, Shenyang, 11001, China
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17
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Yu M, Yang Z, Chen C, Lv Y, Xiang L, Zhao S, Li R. Association of the gallbladder or biliary diseases with dipeptidyl peptidase 4 inhibitors in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Diabetol Metab Syndr 2022; 14:153. [PMID: 36271423 PMCID: PMC9585736 DOI: 10.1186/s13098-022-00924-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 10/13/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Previous studies have shown inconsistent conclusions regarding the association between incretin-based therapies and the risk of developing gallbladder or biliary diseases. We conducted a meta-analysis to evaluate the risk of gallbladder or biliary diseases associated with dipeptidyl peptidase 4 inhibitors (DPP4i) in patients with type 2 diabetes. METHODS The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched (from inception up to March 14, 2022) for published randomized controlled trials (RCTs) that compared DPP4i with placebo or other glucose-lowering drugs in patients with type 2 diabetes. The outcomes of interest were cholecystitis, cholangitis, cholelithiasis, bile duct stones, and biliary colic. Relative risks (RRs) and 95% confidence intervals (CI) were pooled using a random-effects model. Subgroup analyses were performed according to patient age, trial duration, and types of DPP4i. RESULTS In total, 97,150 participants from 75 eligible RCTs were included in the meta-analysis. DPP4i were associated with an increased risk of composite of gallbladder or biliary diseases (RR 1.20 [95% CI 1.01-1.42]) and cholecystitis (RR 1.38 [95% CI 1.08-1.75]). Among all included trials, DPP4i showed no association with the following manifestations of gallbladder or biliary diseases: cholelithiasis (RR 1.00 [95% CI 0.76-1.32]), cholangitis (RR 0.81 [95% CI 0.39-1.66]), bile duct stones (RR 1.08 [95% CI 0.57-2.05]), and biliary colic (RR 0.72 [95% CI 0.23-2.25]). Subgroup analyses showed that DPP4i were associated with a higher risk of cholecystitis in older patients (RR 1.37 [95% CI 1.03-1.83]) compared with younger patients (RR 1.08 [95% CI 0.89-2.18]) and in those with a longer duration of drug use (RR 1.43 [95% CI 1.08-1.89]) compared with shorter use (RR 1.23 [95% CI 0.74-2.03]). CONCLUSIONS This systematic review and meta-analysis of RCTs found that the use of DPP4i was associated with an increased risk of cholecystitis, especially in patients of advanced age or in those who were exposed to the drugs for a long period of time.
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Affiliation(s)
- Meng Yu
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, YouYi Road 1#, Yuzhong District, Chongqing, 400016, China
| | - Zheng Yang
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, YouYi Road 1#, Yuzhong District, Chongqing, 400016, China
| | - Chongxin Chen
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, YouYi Road 1#, Yuzhong District, Chongqing, 400016, China
| | - Yuhuan Lv
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, YouYi Road 1#, Yuzhong District, Chongqing, 400016, China
| | - Linyu Xiang
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, YouYi Road 1#, Yuzhong District, Chongqing, 400016, China
| | - Subei Zhao
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, YouYi Road 1#, Yuzhong District, Chongqing, 400016, China
| | - Rong Li
- Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, YouYi Road 1#, Yuzhong District, Chongqing, 400016, China.
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18
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Alicic R, Nicholas SB. Diabetic Kidney Disease Back in Focus: Management Field Guide for Health Care Professionals in the 21st Century. Mayo Clin Proc 2022; 97:1904-1919. [PMID: 36202498 DOI: 10.1016/j.mayocp.2022.05.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 03/28/2022] [Accepted: 05/03/2022] [Indexed: 12/02/2022]
Abstract
Chronic kidney disease due to diabetes, or diabetic kidney disease (DKD), is a worldwide leading cause of chronic kidney disease and kidney failure and an increasingly important global public health issue. It is associated with poor quality of life, high burden of chronic diseases, and increased risk of premature death. Until recently, people with DKD had limited therapeutic options. Treatments have focused largely on glycemic and blood pressure control and renin-angiotensin system blockade, leaving patients with significant residual risk for progression of DKD. The availability of newer classes of glucose-lowering agents, namely, sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, has changed the therapeutic landscape for these patients. These therapies have offered unprecedented opportunities to reduce the risk for progression of kidney disease and the risk of death that have led to recent updates to clinical guidelines. As such, the American Diabetes Association, the Kidney Disease: Improving Global Outcomes, and the European Association for the Study of Diabetes now recommend the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists for patients with DKD to provide both kidney and cardiovascular protective benefits. This review highlights the importance of early detection of DKD and summarizes the latest recommendations in the clinical guidelines on management of patients with DKD with hope of facilitating their uptake into everyday clinical practice. An integrated approach to patient care with a multidisciplinary focus can help achieve the necessary shift in clinical care of patients with DKD.
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Affiliation(s)
- Radica Alicic
- Providence Medical Research Center, Providence Health Care, University of Washington, Spokane and Seattle
| | - Susanne B Nicholas
- David Geffen School of Medicine at University of California, Los Angeles.
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He L, Wang J, Ping F, Yang N, Huang J, Li W, Xu L, Zhang H, Li Y. Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials. BMJ 2022; 377:e068882. [PMID: 35764326 PMCID: PMC9237836 DOI: 10.1136/bmj-2021-068882] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVE To examine the association between dipeptidyl peptidase-4 inhibitors and gallbladder or biliary diseases. DESIGN Systematic review and pairwise and network meta-analysis. DATA SOURCES PubMed, EMBASE, Web of Science, and CENTRAL from inception until 31 July 2021. ELIGIBILITY CRITERIA Randomised controlled trials of adult patients with type 2 diabetes who received dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors compared with placebo or other antidiabetes drugs. MAIN OUTCOME MEASURES Composite of gallbladder or biliary diseases, cholecystitis, cholelithiasis, and biliary diseases. DATA EXTRACTION AND DATA SYNTHESIS Two reviewers independently extracted the data and assessed the quality of the studies. The quality of the evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework (GRADE) approach. The meta-analysis used pooled odds ratios and 95% confidence intervals. RESULTS A total of 82 randomised controlled trials with 104 833 participants were included in the pairwise meta-analysis. Compared with placebo or non-incretin drugs, dipeptidyl peptidase-4 inhibitors were significantly associated with an increased risk of the composite of gallbladder or biliary diseases (odds ratio 1.22 (95%confidence interval 1.04 to 1.43); risk difference 11 (2 to 21) more events per 10 000 person years) and cholecystitis (odds ratio 1.43 (1.14 to 1.79); risk difference 15 (5 to 27) more events per 10 000 person years) but not with the risk of cholelithiasis and biliary diseases. The associations tended to be observed in patients with a longer duration of dipeptidyl peptidase-4 inhibitor treatment. In the network meta-analysis of 184 trials, dipeptidyl peptidase-4 inhibitors increased the risk of the composite of gallbladder or biliary diseases and cholecystitis compared with sodium-glucose cotransporter-2 inhibitors but not compared with glucagon-like peptide-1 receptor agonists. CONCLUSIONS Dipeptidyl peptidase-4 inhibitors increased the risk of cholecystitis in randomised controlled trials, especially with a longer treatment duration, which requires more attention from physicians in clinical practice. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42021271647.
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Affiliation(s)
- Liyun He
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jialu Wang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Ping
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Na Yang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingyue Huang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Li
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lingling Xu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huabing Zhang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuxiu Li
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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20
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Dong YH, Wu JH, Chang CH, Lin JW, Wu LC, Toh S. Association between glucagon-like peptide-1 receptor agonists and biliary-related diseases in patients with type 2 diabetes: A nationwide cohort study. Pharmacotherapy 2022; 42:483-494. [PMID: 35508702 DOI: 10.1002/phar.2688] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 04/22/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023]
Abstract
STUDY OBJECTIVE Clinical trials have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may be associated with a higher risk of biliary-related diseases in patients with type 2 diabetes. Limited real-world studies have examined the comparative biliary safety of GLP-1RAs versus other antihyperglycemic drugs. We aimed to estimate the comparative risk of biliary-related diseases between GLP-1RAs and sodium glucose cotransporter 2 inhibitors (SGLT2is), which are indicated for patients with similar diabetes severity in Taiwan. DESIGN Retrospective cohort study. DATA SOURCE Taiwan National Health Insurance Database during 2011 to 2018. PATIENTS Patients with type 2 diabetes who initiated GLP-1RAs or SGLT2is. INTERVENTION GLP-1RAs versus SGLT2is. MEASUREMENTS AND MAIN RESULTS We used an on-treatment approach to examine the effect of continuous use and an intention-to-treat approach to assess the effect of initiation of GLP-1RAs versus SGLT2is. We used Coxregression models to estimate the hazard ratios (HRs) and 95% confidenceintervals (CIs) for the composite hospitalized biliary-related diseases, including acute cholecystitis or cholecystectomy, choledocholithiasis, and acute cholangitis, after matching each GLP-1RA initiator to up to 10 SGLT2iinitiators using propensity scores (PSs). Among 78,253 PS-matched patients, GLP-1RA use was associated with a numerically higher risk of biliary-related diseases versus SGLT2i use in the on-treatment analysis, with an HR of 1.20 (95% CI, 0.93-1.56) for the composite outcome, an HR of 1.22 (95% CI, 0.92-1.62) for acute cholecystitis or cholecystectomy, an HR of 1.20 (95% CI, 0.69-2.07) for choledocholithiasis, and an HR of 1.14 (95% CI,0.82-2.42) for acute cholangitis. The HRs were more pronounced in theintention-to-treat analysis (1.27 [95% CI, 1.05-1.53] for the composite outcome, 1.29 [95% CI, 1.04-1.58] foracute cholecystitis or cholecystectomy, 1.74 [95% CI, 1.23-2.46] for choledocholithiasis, and 1.31 [95% CI, 0.89-1.94] for acute cholangitis). The increased risk of the composite outcome associated with GLP-1RAs was more evident in patients aged 〉60 years, women, and 120 days after treatment initiation. Liraglutide, but not dulaglutide, was associated with an elevated risk. CONCLUSIONS GLP-1RAs might be associated with an elevated risk of biliary-related diseases compared to SGLT2is in Asian patients with type 2 diabetes.
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Affiliation(s)
- Yaa-Hui Dong
- Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Hospital and Health Care Administration, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jo-Hsuan Wu
- Shiley Eye Institute and Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center, University of California, San Diego, California, USA
| | - Chia-Hsuin Chang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Jou-Wei Lin
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Douliou City, Taiwan.,Cardiovascular Center, National Taiwan University Hospital Yunlin Branch, Douliou City, Taiwan
| | - Li-Chiu Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Sengwee Toh
- Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA
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21
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He L, Wang J, Ping F, Yang N, Huang J, Li Y, Xu L, Li W, Zhang H. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Intern Med 2022; 182:513-519. [PMID: 35344001 PMCID: PMC8961394 DOI: 10.1001/jamainternmed.2022.0338] [Citation(s) in RCA: 107] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
IMPORTANCE Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been widely recommended for glucose control and cardiovascular risk reduction in patients with type 2 diabetes, and more recently, for weight loss. However, the associations of GLP-1 RAs with gallbladder or biliary diseases are controversial. OBJECTIVE To evaluate the association of GLP-1 RA treatment with gallbladder and biliary diseases and to explore risk factors for these associations. DATA SOURCES MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library (inception to June 30, 2021), websites of clinical trial registries (July 10, 2021), and reference lists. There were no language restrictions. STUDY SELECTION Randomized clinical trials (RCTs) comparing the use of GLP-1 RA drugs with placebo or with non-GLP-1 RA drugs in adults. DATA EXTRACTION AND SYNTHESIS Two reviewers independently extracted data according to the PRISMA recommendations and assessed the quality of each study with the Cochrane Collaboration risk-of-bias tool. Pooled relative risks (RRs) were calculated using random or fixed-effects models, as appropriate. The quality of evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. MAIN OUTCOMES AND MEASURES The primary outcome was the composite of gallbladder or biliary diseases. Secondary outcomes were biliary diseases, biliary cancer, cholecystectomy, cholecystitis, and cholelithiasis. Data analyses were performed from August 5, 2021, to September 3, 2021. RESULTS A total of 76 RCTs involving 103 371 patients (mean [SD] age, 57.8 (6.2) years; 41 868 [40.5%] women) were included. Among all included trials, randomization to GLP-1 RA treatment was associated with increased risks of gallbladder or biliary diseases (RR, 1.37; 95% CI, 1.23-1.52); specifically, cholelithiasis (RR, 1.27; 95% CI, 1.10-1.47), cholecystitis (RR, 1.36; 95% CI, 1.14-1.62), and biliary disease (RR, 1.55; 95% CI, 1.08-2.22). Use of GLP-1 RAs was also associated with increased risk of gallbladder or biliary diseases in trials for weight loss (n = 13; RR, 2.29; 95% CI, 1.64-3.18) and for type 2 diabetes or other diseases (n = 63; RR, 1.27; 95% CI, 1.14-1.43; P <.001 for interaction). Among all included trials, GLP-1 RA use was associated with higher risks of gallbladder or biliary diseases at higher doses (RR, 1.56; 95% CI, 1.36-1.78) compared with lower doses (RR, 0.99; 95% CI, 0.73-1.33; P = .006 for interaction) and with longer duration of use (RR, 1.40; 95% CI, 1.26-1.56) compared with shorter duration (RR, 0.79; 95% CI, 0.48-1.31; P = .03 for interaction). CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis of RCTs found that use of GLP-1 RAs was associated with increased risk of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss. TRIAL REGISTRATION PROSPERO Identifier: CRD42021271599.
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Affiliation(s)
- Liyun He
- Department of Endocrinology, Key Laboratory of Endocrinology of the National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jialu Wang
- Department of Endocrinology, Key Laboratory of Endocrinology of the National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Ping
- Department of Endocrinology, Key Laboratory of Endocrinology of the National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Na Yang
- Department of Endocrinology, Key Laboratory of Endocrinology of the National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingyue Huang
- Department of Endocrinology, Key Laboratory of Endocrinology of the National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuxiu Li
- Department of Endocrinology, Key Laboratory of Endocrinology of the National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lingling Xu
- Department of Endocrinology, Key Laboratory of Endocrinology of the National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wei Li
- Department of Endocrinology, Key Laboratory of Endocrinology of the National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huabing Zhang
- Department of Endocrinology, Key Laboratory of Endocrinology of the National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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22
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Seidu S, Cos X, Brunton S, Harris SB, Jansson SPO, Mata-Cases M, Neijens AMJ, Topsever P, Khunti K. 2022 update to the position statement by Primary Care Diabetes Europe: a disease state approach to the pharmacological management of type 2 diabetes in primary care. Prim Care Diabetes 2022; 16:223-244. [PMID: 35183458 DOI: 10.1016/j.pcd.2022.02.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 01/25/2022] [Accepted: 02/02/2022] [Indexed: 12/12/2022]
Abstract
Type 2 diabetes and its associated comorbidities are growing more prevalent, and the complexity of optimising glycaemic control is increasing, especially on the frontlines of patient care. In many countries, most patients with type 2 diabetes are managed in a primary care setting. However, primary healthcare professionals face the challenge of the growing plethora of available treatment options for managing hyperglycaemia, leading to difficultly in making treatment decisions and contributing to treatment and therapeutic inertia. This position statement offers a simple and patient-centred clinical decision-making model with practical treatment recommendations that can be widely implemented by primary care clinicians worldwide through shared-decision conversations with their patients. It highlights the importance of managing cardiovascular disease and elevated cardiovascular risk in people with type 2 diabetes and aims to provide innovative risk stratification and treatment strategies that connect patients with the most effective care.
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Affiliation(s)
- S Seidu
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, United Kingdom.
| | - X Cos
- Sant Marti de Provenҫals Primary Care Centres, Institut Català de la Salut, University Research Institute in Primary Care (IDIAP Jordi Gol), Barcelona, Spain
| | - S Brunton
- Primary Care Metabolic Group, Winnsboro, SC, USA
| | - S B Harris
- Department of Family Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - S P O Jansson
- School of Medical Sciences, University Health Care Research Centre, Örebro University, Örebro, Sweden
| | - M Mata-Cases
- La Mina Primary Care Centre, Institut Català de la Salut, University Research Institute in Primary Care (IDIAP Jordi Gol), CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
| | - A M J Neijens
- Praktijk De Diabetist, Nurse-Led Case Management in Diabetes, QOL-consultancy, Deventer, The Netherlands
| | - P Topsever
- Department of Family Medicine, Acibadem Mehmet Ali Aydinlar University School of Medicine, Kerem Aydinlar Campus, 34752 Atasehir, Istanbul, Turkey
| | - K Khunti
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, United Kingdom
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23
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Evidence for Cardiorenal Protection with SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Patients with Diabetic Kidney Disease. J Pers Med 2022; 12:jpm12020223. [PMID: 35207711 PMCID: PMC8874759 DOI: 10.3390/jpm12020223] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 01/30/2022] [Accepted: 02/03/2022] [Indexed: 12/11/2022] Open
Abstract
For almost two decades, the management of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) was based on the optimal glycemic and blood pressure control as well as on the adequate blockade of the renin-angiotensin-system. Over the past few years, sodium-glucose co-transporter 2 (SGLT-2) inhibitors and glucagone-like peptide 1 receptor agonists (GLP1-RAs) were added to our therapeutic armarhatum, offering promise for more effective mitigation of the substantial residual cardiorenal risk of these patients. Large randomized controlled trials (RCTs) designed to demonstrate the cardiovascular safety of SGLT-2 inhibitors and GLP1-RAs showed that these novel anti-diabetic medications improve cardiovascular outcomes in patients with T2DM. RCTs conducted specifically in CKD patients with or without T2DM demonstrated that SGLT-2 inhibitors were also effective in retarding the progression of kidney injury to end-stage kidney disease. The kidney protective effects of GLP1-RA are not yet proven, but RCTs are currently ongoing to investigate this crucial research question. In this article, we review the available clinical-trial evidence supporting the use of SGLT-2 inhibitors and GLP1-RAs for cardiorenal protection in patients with T2DM and CKD. We provide clinical practice recommendations for a personalized approach in the use of these novel therapies, according to the severity of CKD and the presence of other cardiometabolic risk factors.
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24
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Abraham G, Easow B, Mathew M, Rajagopalan U, Nagarajan P. Serious adverse effects following use of liraglutide in individuals with type 2 diabetes. JOURNAL OF DIABETOLOGY 2022. [DOI: 10.4103/jod.jod_78_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2023] Open
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25
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Amaro A, Sugimoto D, Wharton S. Efficacy and safety of semaglutide for weight management: evidence from the STEP program. Postgrad Med 2022; 134:5-17. [PMID: 36691309 DOI: 10.1080/00325481.2022.2147326] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Obesity is a global health challenge. It is a multifactorial, complex, and progressive disease associated with various health complications and increased mortality. Lifestyle modifications are central to weight management but may be insufficient to maintain clinically meaningful weight loss. Pharmacotherapies are recommended as an adjunct to lifestyle interventions to induce and sustain clinically meaningful weight loss and reduce the risk of comorbidities in appropriate patients. Glucagon-like peptide-1 is an incretin metabolic hormone responsible for a range of physiological effects, including glucose and appetite regulation. Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been approved for the treatment of type 2 diabetes since 2005 including exenatide (short- and extended-release), lixisenatide, liraglutide, dulaglutide, albiglutide, and semaglutide. Of these, semaglutide (subcutaneous) and liraglutide are currently US Food and Drug Administration (FDA)-approved for chronic weight management in patients with or without diabetes. The phase 3 Semaglutide Treatment Effect in People with obesity (STEP) program was designed to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with overweight or obesity. Following the submission of the results of the STEP 1-4 trials, the FDA approved once-weekly subcutaneous semaglutide 2.4 mg for chronic weight management in people with overweight or obesity in April 2021. Data from the program demonstrated that semaglutide (2.4 mg once weekly) achieved significant and sustained weight loss, together with improvements in cardiometabolic risk factors compared with placebo, and was generally well tolerated, with a safety profile consistent with other GLP-1RAs. The most common adverse events reported in STEP 1-5 were gastrointestinal events, which were transient, mild-to-moderate in severity, and typically resolved without permanent treatment discontinuation. This article reviews the data from STEP 1-5 and highlights clinically relevant findings for primary care providers.
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Affiliation(s)
- Anastassia Amaro
- Penn Metabolic Medicine, Division of Endocrinology, University of Pennsylvania, Philadelphia, PA, USA
| | | | - Sean Wharton
- York University, McMaster University and Wharton Weight Management Clinic, Toronto, Ontario, Canada
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26
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Borderie G, Schnebelen M, Baynat L. Efpeglenatide and Heart and Kidney Outcomes in Type 2 Diabetes. N Engl J Med 2021; 385:2106. [PMID: 34818489 DOI: 10.1056/nejmc2115776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
| | | | - Louise Baynat
- Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
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27
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Abstract
The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is the most recently approved agent of this drug class, and the only GLP-1RA currently available as both subcutaneous and oral formulation. While GLP-1RAs effectively improve glycemic control and cause weight loss, potential safety concerns have arisen over the years. For semaglutide, such concerns have been addressed in the extensive phase 3 registration trials including cardiovascular outcome trials for both subcutaneous (SUSTAIN: Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) and oral (PIONEER: Peptide InnOvatioN for the Early diabEtes tReatment) semaglutide and are being studied in further trials and registries, including real world data studies. In the current review we discuss the occurrence of adverse events associated with semaglutide focusing on hypoglycemia, gastrointestinal side effects, pancreatic safety (pancreatitis and pancreatic cancer), thyroid cancer, gallbladder events, cardiovascular aspects, acute kidney injury, diabetic retinopathy (DRP) complications and injection-site and allergic reactions and where available, we highlight potential underlying mechanisms. Furthermore, we discuss whether effects are specific for semaglutide or a class effect. We conclude that semaglutide induces mostly mild-to-moderate and transient gastrointestinal disturbances and increases the risk of biliary disease (cholelithiasis). No unexpected safety issues have arisen to date, and the established safety profile for semaglutide is similar to that of other GLP-1RAs where definitive conclusions for pancreatic and thyroid cancer cannot be drawn at this point due to low incidence of these conditions. Due to its potent glucose-lowering effect, patients at risk for deterioration of existing DRP should be carefully monitored if treated with semaglutide, particularly if also treated with insulin. Given the beneficial metabolic and cardiovascular actions of semaglutide, and the low risk for severe adverse events, semaglutide has an overall favorable risk/benefit profile for patient with type 2 diabetes.
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Affiliation(s)
| | - Daniël H. Van Raalte
- Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands
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28
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Zhang Z, Du Z, Liu Q, Wu T, Tang Q, Zhang J, Huang C, Huang Y, Li R, Li Y, Zhao Y, Zhang G, Zhou J, Huang H, Fang Z, He J. Glucagon-like peptide 1 analogue prevents cholesterol gallstone formation by modulating intestinal farnesoid X receptor activity. Metabolism 2021; 118:154728. [PMID: 33581130 DOI: 10.1016/j.metabol.2021.154728] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 01/13/2021] [Accepted: 02/07/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Cholesterol gallstone disease (CGD) is a common gastrointestinal disease. Liraglutide, an analogue of glucagon-like peptide 1, has been approved to treat type 2 diabetes. Clinical studies have suggested a potential role of liraglutide in CGD. METHODS Mice were subcutaneously injected with liraglutide, then fed a lithogenic diet. Bile duct cannulation was performed to collect bile output in mice. Intestinal-specific ablation or pharmacological inhibition of farnesoid X receptor (FXR) was used to study its functions in CGD. RESULTS Liraglutide could protect mice against CGD. Liraglutide treatment increased the biliary concentration of cholesterol, phospholipids and bile acids and thereby decreased the cholesterol saturation index. The resistance to CGD conferred by liraglutide is likely a result of increased bile acid synthesis and efficient bile acid transport. The expression of a key bile acid synthetic enzyme, Cyp7a1, was significantly increased in liraglutide-treated mice. The increased expression of Cyp7a1 resulted from a relieved suppression signal of Fgf15 from the ileum. Mechanistically, liraglutide treatment altered bile acid composition and suppressed FXR activity in the ileum. Genetic ablation or pharmacological inhibition of FXR in the intestine protected mice against CGD. More importantly, intestinal FXR was required for liraglutide-mediated regulation of hepatic expression of Cyp7a1. CONCLUSION Liraglutide improved CGD by increasing bile acid secretion and decreasing cholesterol saturation index. Liraglutide attenuates the negative feedback inhibition of bile acids through inhibiting intestinal FXR activity. Our results suggest that liraglutide may represent a novel way for treating or preventing cholesterol gallstones in individuals with high risk of CGD.
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Affiliation(s)
- Zijing Zhang
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Zuo Du
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
| | - Qinhui Liu
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Tong Wu
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Qin Tang
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Jinhang Zhang
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Cuiyuan Huang
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Ya Huang
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Rui Li
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Yanping Li
- Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Yingnan Zhao
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Guorong Zhang
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Jian Zhou
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - Hui Huang
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China
| | - ZhongZe Fang
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China.
| | - Jinhan He
- Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China.
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Kamruzzaman M, Horowitz M, Jones KL, Marathe CS. Gut-Based Strategies to Reduce Postprandial Glycaemia in Type 2 Diabetes. Front Endocrinol (Lausanne) 2021; 12:661877. [PMID: 33897622 PMCID: PMC8062751 DOI: 10.3389/fendo.2021.661877] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Accepted: 03/16/2021] [Indexed: 02/05/2023] Open
Abstract
Postprandial glycemic control is an important target for optimal type 2 diabetes management, but is often difficult to achieve. The gastrointestinal tract plays a major role in modulating postprandial glycaemia in both health and diabetes. The various strategies that have been proposed to modulate gastrointestinal function, particularly by slowing gastric emptying and/or stimulating incretin hormone GLP-1, are summarized in this review.
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Affiliation(s)
- Md Kamruzzaman
- Department of Applied Nutrition and Food Technology, Islamic University, Kushtia, Bangladesh
| | - Michael Horowitz
- Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Karen L. Jones
- Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
| | - Chinmay S. Marathe
- Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia
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Seo YG. Side Effects Associated with Liraglutide Treatment for Obesity as Well as Diabetes. J Obes Metab Syndr 2021; 30:12-19. [PMID: 33071241 PMCID: PMC8017323 DOI: 10.7570/jomes20059] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 06/25/2020] [Accepted: 08/02/2020] [Indexed: 02/06/2023] Open
Abstract
Liraglutide is a glucagon-like peptide-1 receptor agonist used as a treatment for type 2 diabetes mellitus, which has been expanded for use at a higher dose in weight control. Therefore, it is necessary to consider adverse reactions of the drug at high doses as well as at lower doses after the indication has been expanded. Body mass index criteria for patients prescribed the drug in the real world tend to be applied less rigorously, which may increase the number of adverse reactions due to over-prescription. Liraglutide treatment was found effective and safe in some studies, while others have warned about its risks. Therefore, this review summarizes the current data available on side effects associated with liraglutide.
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Affiliation(s)
- Young-Gyun Seo
- Department of Family Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
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Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021; 384:989-1002. [PMID: 33567185 DOI: 10.1056/nejmoa2032183] [Citation(s) in RCA: 2023] [Impact Index Per Article: 505.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODS In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. RESULTS The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). CONCLUSIONS In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).
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Affiliation(s)
- John P H Wilding
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Rachel L Batterham
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Salvatore Calanna
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Melanie Davies
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Luc F Van Gaal
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Ildiko Lingvay
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Barbara M McGowan
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Julio Rosenstock
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Marie T D Tran
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Thomas A Wadden
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Sean Wharton
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Koutaro Yokote
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Niels Zeuthen
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
| | - Robert F Kushner
- From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.)
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Seidu S, Cos X, Brunton S, Harris SB, Jansson SPO, Mata-Cases M, Neijens AMJ, Topsever P, Khunti K. A disease state approach to the pharmacological management of Type 2 diabetes in primary care: A position statement by Primary Care Diabetes Europe. Prim Care Diabetes 2021; 15:31-51. [PMID: 32532635 DOI: 10.1016/j.pcd.2020.05.004] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 04/30/2020] [Accepted: 05/11/2020] [Indexed: 12/31/2022]
Abstract
Type 2 diabetes and its associated comorbidities are growing more prevalent, and the complexity of optimising glycaemic control is increasing, especially on the frontlines of patient care. In many countries, most patients with type 2 diabetes are managed in a primary care setting. However, primary healthcare professionals face the challenge of the growing plethora of available treatment options for managing hyperglycaemia, leading to difficultly in making treatment decisions and contributing to therapeutic inertia. This position statement offers a simple and patient-centred clinical decision-making model with practical treatment recommendations that can be widely implemented by primary care clinicians worldwide through shared-decision conversations with their patients. It highlights the importance of managing cardiovascular disease and elevated cardiovascular risk in people with type 2 diabetes and aims to provide innovative risk stratification and treatment strategies that connect patients with the most effective care.
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Affiliation(s)
- S Seidu
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, United Kingdom.
| | - X Cos
- Sant Marti de Provençals Primary Care Centres, Institut Català de la Salut, University Research Institute in Primary Care (IDIAP Jordi Gol), Barcelona, Spain
| | - S Brunton
- Primary Care Metabolic Group, Los Angeles, CA, USA
| | - S B Harris
- Department of Family Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - S P O Jansson
- School of Medical Sciences, University Health Care Research Centre, Örebro University, Örebro, Sweden
| | - M Mata-Cases
- La Mina Primary Care Centre, Institut Català de la Salut, University Research Institute in Primary Care (IDIAP Jordi Gol), CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain
| | - A M J Neijens
- Praktijk De Diabetist, Nurse-Led Case Management in Diabetes, QOL-consultancy, Deventer, The Netherlands
| | - P Topsever
- Department of Family Medicine, Acibadem Mehmet Ali Aydinlar University School of Medicine, Kerem Aydinlar Campus, Atasehir 34752, Istanbul, Turkey
| | - K Khunti
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, United Kingdom
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Maor Y, Ergaz D, Malnick SDH, Melzer E, Neuman MG. Liraglutide-Induced Hepatotoxicity. Biomedicines 2021; 9:106. [PMID: 33498980 PMCID: PMC7911918 DOI: 10.3390/biomedicines9020106] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/15/2021] [Accepted: 01/18/2021] [Indexed: 12/21/2022] Open
Abstract
A 52-year-old woman with a BMI of 31.2 kg/m2 was treated with the glucagon-like peptide 1 (GLP-1) agonist liraglutide as part of her weight-reduction program. Following this, she developed an idiosyncratic drug-related liver injury (IDILI). Advances in noninvasive techniques enabled this diagnosis to be established. By employing easily quantifiable methods based on serum biomarkers, we could explore a wide variety of endpoints in assessing personalized DILI. In addition, we can test endpoints that are associated with the drug's mechanism of action. Personalized medicine and therapeutic pharmacovigilance of incretin-based hypoglycemic agents are needed to ensure the safety of patients.
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Affiliation(s)
- Yaakov Maor
- Kaplan Medical Center, Institute of Gastroenterology and Hepatology, Hebrew University Medical School of Jerusalem, Rehovot 71600, Israel; (Y.M.); (E.M.)
| | - David Ergaz
- Internal Medicine Day-Care Kaplan Medical Center, Hebrew University Medical School of Jerusalem, Rehovot 71600, Israel;
| | | | - Ehud Melzer
- Kaplan Medical Center, Institute of Gastroenterology and Hepatology, Hebrew University Medical School of Jerusalem, Rehovot 71600, Israel; (Y.M.); (E.M.)
| | - Manuela G. Neuman
- In Vitro Drug Safety and Biotechnology and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON M5G 1L5, Canada
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Tuttolomondo A, Cirrincione A, Casuccio A, Del Cuore A, Daidone M, Di Chiara T, Di Raimondo D, Corte VD, Maida C, Simonetta I, Scaglione S, Pinto A. Efficacy of dulaglutide on vascular health indexes in subjects with type 2 diabetes: a randomized trial. Cardiovasc Diabetol 2021; 20:1. [PMID: 33397395 PMCID: PMC7784355 DOI: 10.1186/s12933-020-01183-5] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 11/27/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Recent cardiovascular outcome trials have shown significant reductions in major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Additionally, adjunctive surrogates for cardiovascular risk validated by some studies include arterial stiffness and endothelial function indexes. To date, no randomized trial has addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damage. AIMS We aimed to evaluate metabolic efficacy and surrogate vascular efficacy endpoints of once-weekly dulaglutide (1.5 mg) plus traditional antidiabetic treatment compared with traditional antidiabetic treatment alone in subjects with type 2 diabetes. METHODS Men and women (aged ≥ 50 years) with established or newly detected type 2 diabetes whose HbA1c level was 9.5% or less on stable doses of up to two oral glucose- lowering drugs with or without basal insulin therapy were eligible for randomization. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness (PWV: pulse wave velocity and augmentation index) and endothelial function (RHI: reactive hyperaemia index) were evaluated at baseline and at three-month and nine-month examination visits. At each visit (at 3 and 9 months), the subjects were also evaluated for glycaemic variables such as fasting plasma glucose (FPG) and HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels. RESULTS At the three-month follow-up, the subjects treated with dulaglutide showed significantly lower serum levels of FPG and HbA1c than control subjects treated with conventional therapy. At the 9-month follow-up, subjects treated with dulaglutide showed significant lower values of the mean diastolic blood pressure, BMI, total serum cholesterol, LDL cholesterol, FPG, HbA1c and PWV and higher mean RHI values than control subjects treated with conventional therapy. CONCLUSIONS Our randomized trial showed that subjects with type 2 diabetes treated with conventional therapy plus 1.5 mg/day of subcutaneous dulaglutide compared with subjects treated with conventional therapy alone showed favourable metabolic effects associated with positive effects on vascular health markers such as arterial stiffness and endothelial function markers. These findings are consistent with previous study findings indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.
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Affiliation(s)
- Antonino Tuttolomondo
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
| | - Anna Cirrincione
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
| | - Alessandra Casuccio
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
| | - Alessandro Del Cuore
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
| | - Mario Daidone
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
| | - Tiziana Di Chiara
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
| | - Domenico Di Raimondo
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
| | - Vittoriano Della Corte
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
- PhD Programme in Molecular and Clinical Medicine, University of Palermo, Piazza delle Cliniche n.2, 90127 Palermo, Italy
| | - Carlo Maida
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
- PhD Programme in Molecular and Clinical Medicine, University of Palermo, Piazza delle Cliniche n.2, 90127 Palermo, Italy
| | - Irene Simonetta
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
| | - Stefania Scaglione
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
| | - Antonio Pinto
- Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D’Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127 Palermo, Italy
- Internal Medicine and Stroke Care Ward, Policlinico ‘P. Giaccone’, Palermo, Italy
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Honigberg MC, Chang LS, McGuire DK, Plutzky J, Aroda VR, Vaduganathan M. Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review. JAMA Cardiol 2020; 5:1182-1190. [PMID: 32584928 PMCID: PMC7744318 DOI: 10.1001/jamacardio.2020.1966] [Citation(s) in RCA: 81] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Importance Recent randomized clinical trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce cardiovascular events in at-risk individuals with type 2 diabetes. Despite these findings, GLP-1RAs are underused in eligible patients, particularly by cardiologists. Observations To date, randomized clinical trials of albiglutide, dulaglutide, liraglutide, and injectable semaglutide have reported favorable cardiovascular outcomes. Most recently approved for clinical use, oral semaglutide has a favorable safety profile and is currently undergoing regulatory evaluation and further study for cardiovascular outcomes. Professional society guidelines now recommend GLP-1RA therapy for cardiovascular risk mitigation in patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors, independent of glucose control or background antihyperglycemic therapy (other diabetes medications being used). Additional conditions suitable for GLP-1RA therapy include obesity and advanced chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2), for which cardiovascular risk-reducing options are limited. Out-of-pocket costs and secondary advantages (eg, weight loss) may inform shared decision-making discussions regarding potential therapies. GLP-1RA therapy has a favorable safety profile. Its most common adverse effect is gastrointestinal upset, which typically wanes during the early weeks of therapy and may be mitigated by starting at the lowest dose and escalating as tolerated. Depending on baseline glycemic control, sulfonylureas and insulin may need to be decreased before GLP-1RA initiation; without concurrent use of insulin or sulfonylureas, GLP-1RAs are not associated with hypoglycemia. Multidisciplinary follow-up and collaborative care with primary care physicians and/or endocrinologists are important. Conclusions and Relevance Findings from this review suggest that GLP-1RAs are safe, are well tolerated, and improve cardiovascular outcomes, largely independent of their antihyperglycemic properties, but they remain underused by cardiologists. This review provides a practical resource for cardiologists for initiating GLP-1RAs and managing the therapy in patients with type 2 diabetes and established ASCVD or high risk for ASCVD.
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Affiliation(s)
| | - Lee-Shing Chang
- Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts
| | - Darren K McGuire
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
| | - Jorge Plutzky
- Division of Cardiovascular Medicine, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts
| | - Vanita R Aroda
- Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts
| | - Muthiah Vaduganathan
- Division of Cardiovascular Medicine, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts
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John M, Gopinath D, Oommen T. Co-Formulations as the First Injectable in Type 2 Diabetes: A Review of Efficacy, Safety, and Implications in Clinical Practice. DUBAI DIABETES AND ENDOCRINOLOGY JOURNAL 2020. [DOI: 10.1159/000509045] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
<b><i>Background:</i></b> Progression of type 2 diabetes will necessitate the use of injectable therapies in a significant number of people. Co-formulations of degludec with liraglutide (IDegLira) and glargine with lixisenatide (IGlarLixi) are currently recommended for intensification in people with type 2 diabetes on basal insulin or glucagon-like peptide receptor agonist (GLP-1RA) alone or in people with type 2 diabetes who are naïve to insulin with very high glycated haemoglobin. Co-formulation of aspart with degludec (IDegAsp) is recommended as a substitute for premixed insulin. The aim of this article is to review the evidence in the use of co-formulations as the first injectable in type 2 diabetes and its clinical implications. <b><i>Summary:</i></b> In people with type 2 diabetes who are naïve to insulin or GLP-1RA, IDegLira and IGlarLixi achieved stable and durable glycaemic control over a wide range of baseline glycated haemoglobin (HbA1c) levels. People on IDegLira and IGlarLixi had lesser risk of hypoglycaemia and weight gain in studies compared to basal insulin and lesser gastrointestinal adverse effects in comparison to GLP-1RA. IDegAsp achieved similar glycaemic control to basal and premixed insulin with lesser risk of nocturnal hypoglycaemia. <b><i>Key Messages:</i></b> IDegLira, IGlarLixi, and IDegAsp can be used as the first injectable in people with type 2 diabetes with very high glycated haemoglobin on oral antidiabetic drugs. These co-formulations combine efficacy and durability with lesser injection burden. The components of these agents have proven cardiovascular and renal safety. Their limitations in flexibility of dosing, renal and cardiovascular considerations, and adverse effects are discussed.
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Li J, Albajrami O, Zhuo M, Hawley CE, Paik JM. Decision Algorithm for Prescribing SGLT2 Inhibitors and GLP-1 Receptor Agonists for Diabetic Kidney Disease. Clin J Am Soc Nephrol 2020; 15:1678-1688. [PMID: 32518100 PMCID: PMC7646234 DOI: 10.2215/cjn.02690320] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Diabetic kidney disease and its comorbid conditions, including atherosclerotic cardiovascular disease, heart failure, diabetes, and obesity, are interconnected conditions that compound the risk of kidney failure and cardiovascular mortality, and exponentiate health care costs. Sodium glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide 1 receptor agonist (GLP-1 RA) are novel diabetes medications that prevent cardiovascular events and kidney failure. Clinical trials exploring the cardiovascular and kidney outcomes of SGLT2i and GLP-1 RA have fundamentally shifted the treatment paradigm of diabetes. Clinical guidelines for diabetes management recommend a more holistic approach beyond glycemic control and emphasize heart and kidney protection of SGLT2i and GLP-1 RA. However, the adoption of prescribing SGLT2i and GLP-1 RA for patients with diabetes and high cardiovascular and kidney risk has been slow. In this review, we provide a decision-making tool to help clinicians determine when to consider SGLT2i and GLP-1 RA for heart and kidney protection. First, we discuss a comprehensive risk assessment for patients with diabetic kidney disease. We compare the effectiveness of SGLT2i and GLP-1 RA for different risk categories. Then, we present a decision algorithm using cardiovascular and kidney failure risk stratification and the strength of current evidence for the use of SGLT2i and GLP-1 RA. Lastly, we review the adverse effects of SGLT2i and GLP-1 RA and propose mitigation strategies.
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Affiliation(s)
- Jiahua Li
- Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts .,Renal Section, Veterans Affairs Boston Healthcare System, Boston, Massachusetts.,Harvard Medical School, Boston, Massachusetts
| | - Oltjon Albajrami
- Renal Section, Veterans Affairs Boston Healthcare System, Boston, Massachusetts.,Renal Division, Department of Medicine, Boston Medical Center, Boston University, Boston, Massachusetts
| | - Min Zhuo
- Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Harvard Medical School, Boston, Massachusetts.,Renal Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.,Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Chelsea E Hawley
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,New England Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts
| | - Julie M Paik
- Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,Renal Section, Veterans Affairs Boston Healthcare System, Boston, Massachusetts.,Harvard Medical School, Boston, Massachusetts.,Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.,New England Geriatric Research Education and Clinical Center, Veterans Affairs Boston Healthcare System, Boston, Massachusetts
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McKee A, Al-Khazaali A, Albert SG. Glucagon-like Peptide-1 Receptor Agonists versus Sodium-Glucose Cotransporter Inhibitors for Treatment of T2DM. J Endocr Soc 2020; 4:bvaa037. [PMID: 32342023 PMCID: PMC7182131 DOI: 10.1210/jendso/bvaa037] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 03/16/2020] [Indexed: 12/25/2022] Open
Abstract
Context Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes. Objective Assist in the prescribing decision regarding severity of illness and risk for adverse events. Design Meta-analysis of the major CVOT and previous meta-analyses. Main Outcome Measures Six trials of GLP-1 RA (51 762 subjects) and 4 trials of SGLT2i (33 457 subjects) showed both drug classes reduced MACE and CVD versus controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: relative rate [rr] MACE 1.09, 95% confidence interval [CI] 0.97, 1.22, P = ns; rr CVD 1.04, 95% CI 0.87, 1.24, P = ns). Hospitalization for heart failure (HHF) improved with SGLT2i (rr 0.68, CI 0.61, 0.76, P < 0.001) but not with GLP-1 RA, (rr 0.93, CI 0.86,1.03, P = ns). Meta-regression suggested benefits of the SGLT2i on CVD and HHF were accentuated with the underlying rate of MACE in the cohort (i.e., >10 events/1000pt*year). GLP-1 RA and SGLT2i showed reduction in renal outcomes (GLP-1 RA rr 0.83, CI 0.75, 0.91, p ≤ 0.001, SGLT2i rr 0.67, CI 0.57, 0.79, P < 0.001) without a preferential difference (GLP-1 RA vs SGLT2i, rr 1.24, CI 0.95, 1.61, P = ns; relative difference (rd) 0.005, CI -0.011, 0.021, P = ns). Serious adverse events for SGLT2i were mycotic genital infections in women (number needed to harm [NNH] = 13 and diabetic ketoacidosis NNH = 595. Gastrointestinal intolerance was the serious adverse event in the GLP1-RA class (NNH = 35). Conclusion GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and renal outcomes. SGLT2i have advantages over GLP-1 RA in reduction in HHF.
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Affiliation(s)
- Alexis McKee
- Division of Endocrinology, Diabetes and Metabolism, Saint Louis University School of Medicine, St. Louis, MO, US
| | - Ali Al-Khazaali
- Division of Endocrinology, Diabetes and Metabolism, Saint Louis University School of Medicine, St. Louis, MO, US
| | - Stewart G Albert
- Division of Endocrinology, Diabetes and Metabolism, Saint Louis University School of Medicine, St. Louis, MO, US
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Skelin M, Rahelić D, Skelin P, Lucijanic M. Comment on Nauck et al. Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events in the LEADER Randomized Trial. Diabetes Care 2019;42:1912-1920. Diabetes Care 2020; 43:e28-e29. [PMID: 31959649 DOI: 10.2337/dc19-2039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Marko Skelin
- Department of Pharmacy, General Hospital Šibenik, Šibenik, Croatia
| | - Dario Rahelić
- University of Zagreb School of Medicine, Zagreb, Croatia.,Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia
| | - Petar Skelin
- Faculty of Medicine, Aalborg University, Denmark
| | - Marko Lucijanic
- Department of Hematology, Dubrava University Hospital, Zagreb, Croatia
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40
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Nauck MA, Kreiner E, Rasmussen S, Saevereid HA, Buse JB. Response to Comment on Nauck et al. Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events in the LEADER Randomized Trial. Diabetes Care 2019;42:1912-1920. Diabetes Care 2020; 43:e30-e31. [PMID: 31959650 PMCID: PMC7411284 DOI: 10.2337/dci19-0067] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Affiliation(s)
- Michael A Nauck
- Diabetes Division, St. Josef-Hospital (Ruhr University), Bochum, Germany
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Chang LS, Vaduganathan M, Plutzky J, Aroda VR. Bridging the Gap for Patients with Diabetes and Cardiovascular Disease Through Cardiometabolic Collaboration. Curr Diab Rep 2019; 19:157. [PMID: 31802265 DOI: 10.1007/s11892-019-1260-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with type 2 diabetes (T2D). Recent cardiovascular outcome trials (CVOTs) have established sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1 RA) as powerful medications that can lower glucose as well as reduce the risk of complications of CVD in many individuals with T2D. The combination of glycemic and cardiovascular benefits of SGLT2i and GLP1 RA has highlighted the importance of collaborative care of patients by diabetes and cardiovascular specialists. We review several models of cardiometabolic care for patients with diabetes and CVD and discuss practical ways in which diabetes and cardiovascular specialists can work together to improve cardiometabolic care. RECENT FINDINGS CVOTs for SGLT2i and GLP1 RA have demonstrated a significant reduction in major adverse cardiovascular events in individuals with T2D and CVD, in addition to their beneficial effects on glucose lowering and weight loss. Additionally, several models of care, including population health screening models with or without a remote management intervention, multidisciplinary clinics, and combined cardiometabolic training, have been proposed to better facilitate the multifaceted care that individuals with diabetes and CVD require. Innovative models of cardiometabolic care have the potential to improve the quality of care that individuals with diabetes and CVD receive. Through collaboration and co-management, diabetes specialists, cardiovascular specialists, and primary care providers have the ability to optimize diabetes and cardiovascular care.
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Affiliation(s)
- Lee-Shing Chang
- Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, RFB-2, Boston, MA, 02115, USA.
| | - Muthiah Vaduganathan
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Jorge Plutzky
- Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Vanita R Aroda
- Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, RFB-2, Boston, MA, 02115, USA
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