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AL-Noshokaty TM, Abdelhamid R, Abdelmaksoud NM, Khaled A, Hossam M, Ahmed R, Saber T, Khaled S, Elshaer SS, Abulsoud AI. Unlocking the multifaceted roles of GLP-1: Physiological functions and therapeutic potential. Toxicol Rep 2025; 14:101895. [PMID: 39911322 PMCID: PMC11795145 DOI: 10.1016/j.toxrep.2025.101895] [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: 11/02/2024] [Revised: 12/30/2024] [Accepted: 01/03/2025] [Indexed: 02/07/2025] Open
Abstract
Glucagon (GCG) like peptide 1 (GLP-1) has emerged as a powerful player in regulating metabolism and a promising therapeutic target for various chronic diseases. This review delves into the physiological roles of GLP-1, exploring its impact on glucose homeostasis, insulin secretion, and satiety. We examine the compelling evidence supporting GLP-1 receptor agonists (GLP-1RAs) in managing type 2 diabetes (T2D), obesity, and other diseases. The intricate molecular mechanisms underlying GLP-1RAs are explored, including their interactions with pathways like extracellular signal-regulated kinase 1/2 (ERK1/2), activated protein kinase (AMPK), cyclic adenine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and protein kinase C (PKC). Expanding our understanding, the review investigates the potential role of GLP-1 in cancers. Also, microribonucleic acid (RNA) (miRNAs), critical regulators of gene expression, are introduced as potential modulators of GLP-1 signaling. We delve into the link between miRNAs and T2D obesity and explore specific miRNA examples influencing GLP-1R function. Finally, the review explores the rationale for seeking alternatives to GLP-1RAs and highlights natural products with promising GLP-1 modulatory effects.
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Affiliation(s)
- Tohada M. AL-Noshokaty
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Rehab Abdelhamid
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | | | - Aya Khaled
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Mariam Hossam
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Razan Ahmed
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Toka Saber
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Shahd Khaled
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
| | - Shereen Saeid Elshaer
- Department of Biochemistry, Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, Egypt
| | - Ahmed I. Abulsoud
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo 11231, Egypt
- Faculty of Pharmacy, Heliopolis University, Cairo 11785, Egypt
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Kamrul-Hasan ABM, Ganakumar V, Nagendra L, Dutta D, Islam MR, Pappachan JM. Effect of beinaglutide, a thrice-daily GLP-1 receptor agonist, on body weight and metabolic parameters: A systematic review and meta-analysis. World J Diabetes 2025; 16:103244. [DOI: 10.4239/wjd.v16.i5.103244] [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: 11/12/2024] [Revised: 02/12/2025] [Accepted: 02/25/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Beinaglutide, a short-acting glucagon-like polypeptide-1 receptor agonist, has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials (RCTs).
AIM To summarize the therapeutic effects of beinaglutide in patients with overweight/obesity with/without type 2 diabetes.
METHODS RCTs involving patients receiving beinaglutide in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases. The change from baseline in body weight was the primary outcome; secondary outcomes included changes in body mass index (BMI), waist circumference (WC), blood pressure, glycemic parameters, lipids, and adverse events (AEs). RevMan web was used to conduct meta-analysis using random-effects models. Outcomes were presented as mean differences (MDs), odds ratios (ORs), or risk ratios (RRs) with 95% confidence intervals (95%CIs).
RESULTS Six RCTs (n = 800) with mostly some concerns about the risk of bias were included. Over 12-24 weeks, beinaglutide 0.1-0.2 mg thrice daily was superior to the control group in reducing total (MD = -3.25 kg, 95%CI: -4.52 to -1.98, I2 = 84%, P < 0.00001) and percent (MD = -4.13%, 95%CI: -4.87 to -3.39, I2 = 54%, P < 0.00001) body weight reduction. Beinaglutide also outperformed the control group in achieving weight loss by 5% (OR 4.61) and 10% (OR = 5.34). The superiority of beinaglutide vs the control group was also found in reducing BMI (MD = -1.22 kg/m2, 95%CI: -1.67 to -0.77) and WC (MD = -2.47 cm, 95%CI: -3.74 to -1.19]). Beinaglutide and the control group had comparable impacts on blood pressure, glycemic parameters, insulin resistance, hepatic transaminases, and lipid profile. Beinaglutide posed higher risks of treatment discontinuation due to AEs (RR = 3.15), nausea (RR = 4.51), vomiting (RR = 8.19), palpitation (RR = 3.95), headache (RR = 2.87), and dizziness (RR = 6.07) than the control. However, the two groups had identical risks of total and serious AEs, diarrhea, fatigue, and hypoglycemia.
CONCLUSION Short-term data from RCTs suggested that beinaglutide causes modest benefits in reducing body weight, BMI, and WC, with no significant difference in glycemic and other metabolic endpoints compared to the control arm. Safety data were consistent with those of the other drugs in the glucagon-like polypeptide-1 receptor agonist class. Larger RCTs are warranted to prove the longer-term metabolic benefits of beinaglutide.
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Affiliation(s)
| | - Vanishri Ganakumar
- Department of Endocrinology, Jawaharlal Nehru Medical College, Belagavi 590010, Karnataka, India
| | - Lakshmi Nagendra
- Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, Karnataka, India
| | - Deep Dutta
- Department of Endocrinology, CEDAR Superspeciality Healthcare, New Delhi 110075, Delhi, India
| | - M Rafiqul Islam
- Department of Internal Medicine, Shaheed Suhrawardy Medical College Hospital, Dhaka 1207, Bangladesh
| | - Joseph M Pappachan
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, United Kingdom
- Department of Endocrinology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India
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Poshtdar S, Rohani P, Ahrabi A, Panahi N, Sohouli MH. The effects of Beinaglutide on obesity and related factors: a systematic review and meta-analysis of randomized controlled trials. Expert Rev Endocrinol Metab 2025:1-10. [PMID: 40214160 DOI: 10.1080/17446651.2025.2491404] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Accepted: 03/21/2025] [Indexed: 04/22/2025]
Abstract
BACKGROUND Considering the important role of obesity and related factors in different societies on increasing the burden of non-communicable diseases, in this review we will investigate the possible effects of Beinaglutide on these risk factors. RESEARCH DESIGN AND METHODS In order to identify all randomized controlled trials that investigated the effects of Beinaglutide on cardiometabolic factors, a systematic search was conducted in the original databases using predefined keywords until July 2024. The pooled weighted mean difference (WMD) and 95% confidence intervals were computed using the random-effects model. RESULTS A quantitative meta-analysis results from seven studies with 872 participants showed that Beinaglutide has a significant lowering effect on weight (WMD: -3.74 kg; 95% CI: -5.03, -2.45), body mass index (BMI) (WMD:-1.64 kg/m2; 95% CI: -2.10, -1.17), waist circumference (WC) (WMD: -3.19 cm; 95% CI: -4.65 to -1.73), triglyceride (TG) levels (WMD: -0.14 mmol/l with; 95% CI: -0.25, -0.04), and systolic blood pressure (SBP) (WMD: -1.76 mm/Hg; 95% CI: -2.61, -0.91). In addition, body weight loss was greater in doses < 0.4 mg compared to doses ≥ 0.4 mg. CONCLUSIONS The results of this meta-analysis show that Beinaglutide is effective in reducing parameters related to obesity, TG as well as SBP.
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Affiliation(s)
- Sepideh Poshtdar
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Pejman Rohani
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Amirali Ahrabi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Nekoo Panahi
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular -Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hassan Sohouli
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
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Yang X, Lin R, Feng C, Kang Q, Yu P, Deng Y, Jin Y. Research Progress on Peptide Drugs for Type 2 Diabetes and the Possibility of Oral Administration. Pharmaceutics 2024; 16:1353. [PMID: 39598478 PMCID: PMC11597531 DOI: 10.3390/pharmaceutics16111353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/10/2024] [Accepted: 10/21/2024] [Indexed: 11/29/2024] Open
Abstract
Diabetes is a global disease that can lead to a range of complications. Currently, the treatment of type 2 diabetes focuses on oral hypoglycemic drugs and insulin analogues. Studies have shown that drugs such as oral metformin are useful in the treatment of diabetes but can limit the liver's ability to release sugar. The development of glucose-lowering peptides has provided new options for the treatment of type 2 diabetes. Peptide drugs have low oral utilization due to their easy degradation, short half-life, and difficulty passing through the intestinal mucosa. Therefore, improving the oral utilization of peptide drugs remains an urgent problem. This paper reviews the research progress of peptide drugs in the treatment of diabetes mellitus and proposes that different types of nano-formulation carriers, such as liposomes, self-emulsifying drug delivery systems, and polymer particles, should be combined with peptide drugs for oral administration to improve their absorption in the gastrointestinal tract.
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Affiliation(s)
- Xinxin Yang
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (X.Y.); (R.L.)
| | - Ruiting Lin
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (X.Y.); (R.L.)
| | - Changzhuo Feng
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China; (C.F.); (Q.K.); (P.Y.)
| | - Qiyuan Kang
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China; (C.F.); (Q.K.); (P.Y.)
| | - Peng Yu
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, China; (C.F.); (Q.K.); (P.Y.)
| | - Yongzhi Deng
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (X.Y.); (R.L.)
| | - Ye Jin
- School of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China; (X.Y.); (R.L.)
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Zheng Z, Zong Y, Ma Y, Tian Y, Pang Y, Zhang C, Gao J. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Signal Transduct Target Ther 2024; 9:234. [PMID: 39289339 PMCID: PMC11408715 DOI: 10.1038/s41392-024-01931-z] [Citation(s) in RCA: 109] [Impact Index Per Article: 109.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 06/17/2024] [Accepted: 07/16/2024] [Indexed: 09/19/2024] Open
Abstract
The glucagon-like peptide-1 (GLP-1) receptor, known as GLP-1R, is a vital component of the G protein-coupled receptor (GPCR) family and is found primarily on the surfaces of various cell types within the human body. This receptor specifically interacts with GLP-1, a key hormone that plays an integral role in regulating blood glucose levels, lipid metabolism, and several other crucial biological functions. In recent years, GLP-1 medications have become a focal point in the medical community due to their innovative treatment mechanisms, significant therapeutic efficacy, and broad development prospects. This article thoroughly traces the developmental milestones of GLP-1 drugs, from their initial discovery to their clinical application, detailing the evolution of diverse GLP-1 medications along with their distinct pharmacological properties. Additionally, this paper explores the potential applications of GLP-1 receptor agonists (GLP-1RAs) in fields such as neuroprotection, anti-infection measures, the reduction of various types of inflammation, and the enhancement of cardiovascular function. It provides an in-depth assessment of the effectiveness of GLP-1RAs across multiple body systems-including the nervous, cardiovascular, musculoskeletal, and digestive systems. This includes integrating the latest clinical trial data and delving into potential signaling pathways and pharmacological mechanisms. The primary goal of this article is to emphasize the extensive benefits of using GLP-1RAs in treating a broad spectrum of diseases, such as obesity, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases, musculoskeletal inflammation, and various forms of cancer. The ongoing development of new indications for GLP-1 drugs offers promising prospects for further expanding therapeutic interventions, showcasing their significant potential in the medical field.
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Affiliation(s)
- Zhikai Zheng
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Yao Zong
- Centre for Orthopaedic Research, Medical School, The University of Western Australia, Nedlands, WA, 6009, Australia
| | - Yiyang Ma
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Yucheng Tian
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Yidan Pang
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Changqing Zhang
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
| | - Junjie Gao
- Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
- Institute of Microsurgery on Extremities, and Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
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Haber R, Zarzour F, Ghezzawi M, Saadeh N, Bacha DS, Al Jebbawi L, Chakhtoura M, Mantzoros CS. The impact of metformin on weight and metabolic parameters in patients with obesity: A systematic review and meta-analysis of randomized controlled trials. Diabetes Obes Metab 2024; 26:1850-1867. [PMID: 38468148 DOI: 10.1111/dom.15501] [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: 09/09/2023] [Revised: 01/15/2024] [Accepted: 01/30/2024] [Indexed: 03/13/2024]
Abstract
There are conflicting data on the weight-reducing potential of metformin (MTF) in nondiabetic patients with obesity. The purpose of this systematic review and meta-analysis was to evaluate the effect of MTF on weight and cardiometabolic parameters in adults with overweight/obesity with or without nonalcoholic fatty liver disease (NAFLD) (CRD42018085512). We included randomized controlled trials (RCTs) in adults without diabetes mellitus, with mean body mass index (BMI) ≥ 25 kg/m2, with or without NAFLD, comparing MTF to placebo/control, lifestyle modification (LSM) or a US Food and Drug Administration-approved anti-obesity drug, reporting on weight or metabolic parameters, and extending over at least 3 months. We conducted a systematic search in MEDLINE, EMBASE, PubMed and the Cochrane Library without time limitation (until March 2022). We screened and selected eligible articles, abstracted relevant data, and assessed the risk of bias. All steps were in duplicate and independently. We conducted a random-effects model meta-analysis using Review Manager version 5.3, with prespecified subgroup analyses in case of heterogeneity. We identified 2650 citations and included 49 trials (55 publications). Compared to placebo, MTF was associated with a significant reduction in BMI (mean difference [MD] -0.56 [-0.74, -0.37] kg/m2; p < 0.0001), at doses ranging from 500 to 2550 mg/day, and with a significant percentage change in BMI of -2.53% (-2.90, -2.17) at the dose 1700 mg/day. There was no interaction by baseline BMI, MTF dose or duration, nor presence or absence of NAFLD. There was no significant difference between MTF and LSM. Orlistat was more effective than MTF (at doses of 1000-1700 mg/day) in terms of weight loss, with an MD in BMI of -3.17 (-5.88; -0.47) kg/m2, favouring the former. Compared to placebo/control, MTF improved insulin parameters, while no effect was detected when compared to LSM. A few small trials showed heterogenous effects on liver parameters in patients with NAFLD treated with MTF compared to placebo/control. There was a large variability in the expression of outcome measures and RCTs were of low quality. In conclusion, MTF was associated with a modest weight reduction in obese nondiabetic patients. Further high-quality and better powered studies are needed to examine the impact of MTF in patients with insulin resistance and NAFLD.
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Affiliation(s)
- Rachelle Haber
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Fatima Zarzour
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Malak Ghezzawi
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Natalie Saadeh
- Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Dania S Bacha
- Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Lama Al Jebbawi
- Faculty of Medicine, American University of Beirut Medical Center, Beirut, Lebanon
| | - Marlene Chakhtoura
- Department of Internal Medicine, Division of Endocrinology, American University of Beirut Medical Center, Beirut, Lebanon
| | - Christos S Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Boston VA Healthcare System, Boston, Massachusetts, USA
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Chen K, Chen L, Shan Z, Wang G, Qu S, Qin G, Yu X, Xin W, Hsieh TH, Mu Y. Beinaglutide for weight management in Chinese individuals with overweight or obesity: A phase 3 randomized controlled clinical study. Diabetes Obes Metab 2024; 26:690-698. [PMID: 37945546 DOI: 10.1111/dom.15360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 10/11/2023] [Accepted: 10/20/2023] [Indexed: 11/12/2023]
Abstract
AIM To investigate the efficacy and safety of beinaglutide as an adjunct to lifestyle intervention among non-diabetic Chinese individuals with overweight or obesity. METHODS This multicentre, randomized, double-blind, placebo-controlled trial (ChiCTR1900023428) included 427 Chinese adults with a body mass index of 28 kg/m2 or higher (obesity) or 24-27.9 kg/m2 (overweight) with weight-related complications. Patients were randomized in a 2:1 ratio to receive 0.2 mg of beinaglutide (subcutaneous) thrice daily or placebo for 16 weeks. Co-primary endpoints were body weight change and the proportion of patients with a weight reduction of 5% or more. RESULTS Mean body weight change from baseline to week 16 was -6.0% and -2.4% in the beinaglutide (n = 282) and placebo (n = 138) groups, respectively; the mixed model repeated measures difference was -3.6% (95% confidence interval: -4.6% to -2.6%; P < .0001). At week 16, more beinaglutide-treated patients achieved a weight reduction of 5% or more (58.2% vs. 25.4% [placebo], odds ratio: 4.4; P < .0001) and of 10% or more (21.3% vs. 5.1% [placebo], odds ratio: 5.5; P < .0001). Beinaglutide also resulted in greater waist circumference reduction (difference: -1.81 cm; P < .01). The weight regain rate 12 weeks after beinaglutide treatment was 0.78%. Nausea (transient and mild-to-moderate) was the most common adverse event in the beinaglutide group (49.3% vs. 7.1% [placebo]). More patients receiving beinaglutide discontinued treatment because of adverse events (5.9% vs. 0.7% [placebo]). Pancreatitis or an increased resting heart rate was not observed in the beinaglutide group. CONCLUSION Beinaglutide combined with lifestyle intervention resulted in significant and clinically meaningful weight reduction with good tolerance in non-diabetic Chinese individuals with overweight or obesity.
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Affiliation(s)
- Kang Chen
- The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Li Chen
- Qilu Hospital of Shandong University, Jinan, China
| | - Zhongyan Shan
- The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Guixia Wang
- The First Hospital of Jilin University, Jilin, China
| | - Shen Qu
- Shanghai Tenth People's Hospital, Shanghai, China
| | - Guijun Qin
- The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xuefeng Yu
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weiquan Xin
- Shanghai Benemae Pharmaceutical Corporation, Shanghai, China
| | - Tsung-Han Hsieh
- Shanghai Benemae Pharmaceutical Corporation, Shanghai, China
| | - Yiming Mu
- The First Medical Center of Chinese PLA General Hospital, Beijing, China
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Han CY, Lu JP, Ye XM, Jin HY, Xu WW, Wang P, Zhang M. Effect of beinaglutide combined with metformin versus aspart 30 with metformin on metabolic profiles and antidrug antibodies in patients with type 2 diabetes: a randomized clinical trial. Front Endocrinol (Lausanne) 2023; 14:1267503. [PMID: 38125788 PMCID: PMC10731293 DOI: 10.3389/fendo.2023.1267503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 11/17/2023] [Indexed: 12/23/2023] Open
Abstract
Objective This prospective study aimed to evaluate the effect of beinaglutide combined with metformin versus aspart 30 with metformin on metabolic profiles and antidrug antibodies (ADAs) in patients with type 2 diabetes (T2D). Methods A total of 134 eligible participants were randomly assigned to the test group and the control group. Patients in the test group were treated with beinaglutide and metformin, whereas patients in the control group were randomly treated with aspart 30 and metformin, with a follow-up period of 6 months. The metabolic profiles and ADAs over 6 months were evaluated. Results After 6 months, 101 (75.37%) patients completed the study. Compared with the control group, the beinaglutide group had significant reductions in 2-h postprandial blood glucose (2hBG) and low blood glucose index (LBGI). Glycated hemoglobin (HbA1c) decreased in both groups relative to baseline. In the test group, one had treatment-emergent beinaglutide ADAs. Significant reductions in triglycerides (TG), non-fasting TG, weight, waist circumference (WC), and body mass index (BMI) were observed. The values of insulin sensitivity index (HOMA-IR) were decreased to a statistically higher degree with beinaglutide treatment. Conclusion Beinaglutide reduces metabolic dysfunction, LBGI, and weight in patients of T2D with a low risk of ADAs. Beinaglutide may offer the potential for a disease-modifying intervention in cardiovascular disease (CVD). Clinical trial registration www.chictr.org.cn, identifier ChiCTR2200061003.
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Affiliation(s)
| | | | | | | | | | | | - Min Zhang
- Department of Endocrinology, Qingpu Hospital Affiliated to Fudan University, Shanghai, China
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Liu X, Yang W, Liu J, Huang X, Fang Y, Ming J, Lai J, Fu J, Ji Q, Wang L. The efficacy and safety of beinaglutide alone or in combination with insulin glargine in Chinese patients with type 2 diabetes mellitus who are inadequately controlled with oral antihyperglycemic therapy: A multicenter, open-label, randomized trial. J Diabetes 2023; 16:e13483. [PMID: 37864379 PMCID: PMC10850920 DOI: 10.1111/1753-0407.13483] [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: 03/24/2023] [Revised: 09/03/2023] [Accepted: 09/24/2023] [Indexed: 10/22/2023] Open
Abstract
BACKGROUND To compare glycemic control in Chinese patients with type 2 diabetes mellitus (T2DM) whose blood glucose levels were inadequately controlled with oral antidiabetic drugs after beinaglutide alone or combined with insulin glargine (IGlar). METHODS In this 16-week multicenter, randomized clinical trial, 68 participants randomly received beinaglutide or IGlar for 8 weeks, then the two drugs in combination for 8 weeks. The primary outcomes were the proportion of individuals achieving their glycemic target and the change in glucose variability as measured with a continuous glucose monitoring system from baseline to 8 and 16 weeks. RESULTS Both the beinaglutide and IGlar groups showed increased proportions achieving their glycemic target at 8 weeks, and the combination augmented the proportion reaching the glycated hemoglobin target from 25.42% at 8 weeks to 40.68% at 16 weeks. The beinaglutide group showed a significant reduction in body weight, body mass index, waist circumference, and systolic blood pressure. Beinaglutide elevated high-density lipoprotein cholesterol by 0.08 mmol/L (95% confidence interval [CI], 0.00-0.16), and diminished low-density lipoprotein cholesterol by 0.21 mmol/L (95% CI, 0.05-0.48), whereas IGlar showed no effect. Though IGlar was more efficient in lowering fasting plasma glucose than beinaglutide at comparable efficacies (to -1.57 mmol/L [95% CI, -2.60 to -0.54]), this difference was abolished in patients whose fasting C-peptide was ≥0.9 ng/mL. CONCLUSION Beinaglutide exhibited a favorable hypoglycemic effect on patients with T2DM, and in combination with IGlar, glucose level was further decreased. Low fasting C-peptide in patients may reduce the glycemic response to beinaglutide therapy. We recommend that C-peptide levels be evaluated when using or switching to the novel glucagon-like peptide-1 receptor agonists beinaglutide. TRIAL REGISTRATION ClinicalTrials.gov: NCT03829891.
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Affiliation(s)
- Xiangyang Liu
- Department of Endocrinology, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Wenjuan Yang
- Department of EndocrinologyShaanxi Aerospace HospitalXi'anChina
| | - Jianrong Liu
- Department of EndocrinologyXi'an Chang An HospitalXi'anChina
| | - Xinxi Huang
- Department of Endocrinology, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Yujie Fang
- Department of Endocrinology, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Jie Ming
- Department of Endocrinology, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Jingbo Lai
- Department of Endocrinology, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Jianfang Fu
- Department of Endocrinology, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Qiuhe Ji
- Department of Endocrinology, Xijing HospitalAir Force Medical UniversityXi'anChina
| | - Li Wang
- Department of Endocrinology, Xijing HospitalAir Force Medical UniversityXi'anChina
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Dutta S, Shah RB, Singhal S, Dutta SB, Bansal S, Sinha S, Haque M. Metformin: A Review of Potential Mechanism and Therapeutic Utility Beyond Diabetes. Drug Des Devel Ther 2023; 17:1907-1932. [PMID: 37397787 PMCID: PMC10312383 DOI: 10.2147/dddt.s409373] [Citation(s) in RCA: 60] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 06/10/2023] [Indexed: 07/04/2023] Open
Abstract
Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin's neuroprotective role in Parkinson's disease, Alzheimer's disease, multiple sclerosis and Huntington's disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.
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Affiliation(s)
- Siddhartha Dutta
- Department of Pharmacology, All India Institute of Medical Sciences, Rajkot, Gujarat, India
| | - Rima B Shah
- Department of Pharmacology, All India Institute of Medical Sciences, Rajkot, Gujarat, India
| | - Shubha Singhal
- Department of Pharmacology, All India Institute of Medical Sciences, Rajkot, Gujarat, India
| | - Sudeshna Banerjee Dutta
- Department of Medical Surgical Nursing, Shri Anand Institute of Nursing, Rajkot, Gujarat, 360005, India
| | - Sumit Bansal
- Department of Anaesthesiology, All India Institute of Medical Sciences, Rajkot, Gujarat, India
| | - Susmita Sinha
- Department of Physiology, Khulna City Medical College and Hospital, Khulna, Bangladesh
| | - Mainul Haque
- Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur, 57000, Malaysia
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11
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Wang JY, Wang QW, Yang XY, Yang W, Li DR, Jin JY, Zhang HC, Zhang XF. GLP-1 receptor agonists for the treatment of obesity: Role as a promising approach. Front Endocrinol (Lausanne) 2023; 14:1085799. [PMID: 36843578 PMCID: PMC9945324 DOI: 10.3389/fendo.2023.1085799] [Citation(s) in RCA: 99] [Impact Index Per Article: 49.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/02/2023] [Indexed: 02/04/2023] Open
Abstract
Obesity is a complex disease characterized by excessive fat accumulation which is caused by genetic, environmental and other factors. In recent years, there has been an increase in the morbidity, disability rate,and mortality due to obesity, making it great threat to people's health and lives, and increasing public health care expenses. Evidence from previous studies show that weight loss can significantly reduce the risk of obesity-related complications and chronic diseases. Diet control, moderate exercise, behavior modification programs, bariatric surgery and prescription drug treatment are the major interventions used to help people lose weight. Among them, anti-obesity drugs have high compliance rates and cause noticeable short-term effects in reducing obese levels. However, given the safety or effectiveness concerns of anti-obesity drugs, many of the currently used drugs have limited clinical use. Glucagon-like peptide-1 receptor (GLP-1R) agonists are a group of drugs that targets incretin hormone action, and its receptors are widely distributed in nerves, islets, heart, lung, skin, and other organs. Several animal experiments and clinical trials have demonstrated that GLP-1R agonists are more effective in treating or preventing obesity. Therefore, GLP-1R agonists are promising agents for the treatment of obese individuals. This review describes evidence from previous research on the effects of GLP-1R agonists on obesity. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop obesity treatments based on GLP-1R agonists.
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Affiliation(s)
- Jing-Yue Wang
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
| | - Quan-Wei Wang
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
| | - Xin-Yu Yang
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
| | - Wei Yang
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
| | - Dong-Rui Li
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
| | - Jing-Yu Jin
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
| | - Hui-Cong Zhang
- Department of Cardiovascular Medicine, The First Hospital of Jilin University, Changchun, China
| | - Xian-Feng Zhang
- Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China
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Pharmacological Treatments and Natural Biocompounds in Weight Management. Pharmaceuticals (Basel) 2023; 16:ph16020212. [PMID: 37139804 PMCID: PMC9962258 DOI: 10.3390/ph16020212] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/25/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023] Open
Abstract
The obesity pandemic is one of society’s most urgent public health concerns. One-third of the global adult population may fall under obese or overweight by 2025, suggesting a rising demand for medical care and an exorbitant cost of healthcare expenditure in the coming years. Generally, the treatment strategy for obese patients is largely patient-centric and needs dietary, behavioral, pharmacological, and sometimes even surgical interventions. Given that obesity cases are rising in adults and children and lifestyle modifications have failed to produce the desired results, the need for medical therapy adjunct to lifestyle modifications is vital for better managing obesity. Most existing or past drugs for obesity treatment target satiety or monoamine pathways and induce a feeling of fullness in patients, while drugs such as orlistat are targeted against intestinal lipases. However, many medications targeted against neurotransmitters showed adverse events in patients, thus being withdrawn from the market. Alternatively, the combination of some drugs has been successfully tested in obesity management. However, the demand for novel, safer, and more efficacious pharmaceutical medicines for weight management does exist. The present review elucidates the current understanding of the available anti-obesity medicines of synthetic and natural origin, their main mechanisms of action, and the shortcomings associated with current weight management drugs.
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