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Home P, Lauand F, Djaballah K, Li X, Hafidh K, Mehta R, Faraoun K, Anaforoğlu İ, Serafini P, Pourrahmat M. Efficacy and safety of iGlarLixi versus IDegAsp in people with type 2 diabetes inadequately controlled with basal insulin: A systematic literature review and network meta-analysis of non-Asian studies. Diabetes Obes Metab 2025; 27:3410-3418. [PMID: 40176458 PMCID: PMC12046479 DOI: 10.1111/dom.16360] [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: 12/17/2024] [Revised: 03/05/2025] [Accepted: 03/12/2025] [Indexed: 04/04/2025]
Abstract
AIMS To estimate the relative treatment effect of iGlarLixi (a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide) versus premixed insulin IDegAsp (insulin degludec plus insulin aspart) in people with type 2 diabetes (T2D) who advanced from basal insulin to iGlarLixi or IDegAsp in non-Asian studies. MATERIALS AND METHODS Randomized controlled trials (RCTs) were identified in a systematic review by searching Embase (including congress abstracts from 2021 to 2023), MEDLINE® and CENTRAL on 10 October 2023. Treatment outcomes from non-Asian RCTs for people with T2D previously treated with basal insulin, who switched to iGlarLixi or IDegAsp, were compared using a network meta-analysis (NMA). Data analysis was performed using R, version 4.0.2. RESULTS The NMA included four RCTs (N = 2535). The results of the NMA showed that iGlarLixi (n = 810) was associated with a significantly greater reduction in HbA1c versus IDegAsp (n = 454) (mean difference [MD]: -0.39 [95% credible interval, CrI: -0.58, -0.21] %-units). iGlarLixi was also associated with a significantly greater likelihood of achieving an HbA1c of <7.0% (risk ratio: 1.42, 95% CrI: 1.18, 1.71). A greater reduction in postprandial glucose was observed with iGlarLixi versus IDegAsp (MD: -1.38 [95% CrI: -2.15, -0.63] mmol/L). A body weight benefit that favoured iGlarLixi versus IDegAsp was documented (MD: -1.54 [95% CrI: -2.26, -0.84] kg). Hypoglycaemia evaluation was inconclusive due to definitional differences between trials. CONCLUSIONS Once-daily iGlarLixi was associated with superior blood glucose control and body weight benefit compared with IDegAsp in insulin-experienced populations with T2D in non-Asian RCTs.
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Affiliation(s)
- Philip Home
- Translational and Clinical Research InstituteNewcastle UniversityNewcastle upon TyneUK
| | | | | | | | - Khadija Hafidh
- Department of Internal Medicine, Diabetology Unit, Rashid HospitalDubai Health AuthorityDubaiUnited Arab Emirates
| | - Roopa Mehta
- Departamento de Endocrinología y Metabolismo, UIEMInstituto Nacional de Ciencias Médicas y Nutrición, Salvador ZubiránMéxico CityMexico
| | | | - İnan Anaforoğlu
- Faculty of MedicineMehmet Ali Aydınlar Acıbadem UniversityIstanbulTurkey
| | - Paul Serafini
- Evidinno Outcomes Research IncVancouverBritish ColumbiaCanada
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Guo L, Chen L, Zhao F, Liu X, Ding H, Wang K, Zhong X, Shankarappa VB, Chaudhary G. Improved glycaemic control in people with type 2 diabetes initiating or switching to IDegAsp in a real-world setting in China. Diabetes Obes Metab 2025; 27:1388-1396. [PMID: 39703112 PMCID: PMC11802397 DOI: 10.1111/dom.16139] [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: 09/04/2024] [Revised: 11/22/2024] [Accepted: 12/02/2024] [Indexed: 12/21/2024]
Abstract
AIMS To investigate glycaemic control in Chinese adults with type 2 diabetes (T2D) initiating, or switching to insulin degludec/insulin aspart (IDegAsp), a co-formulation of basal, and bolus insulin, in a real-world setting. MATERIALS AND METHODS A 20-week, prospective, single-arm, open-label, non-interventional study was conducted in Chinese adults with T2D initiating, or switching to IDegAsp after anti-hyperglycaemic treatment with oral antidiabetic drugs (OADs), other insulins, or glucagon-like peptide-1 receptor agonists. The primary endpoint was a change in HbA1c from baseline to end of the study; the secondary endpoints included a change in fasting plasma glucose and Diabetes Treatment Satisfaction Questionnaire (DTSQ) score. RESULTS Significant reductions were observed in mean HbA1c and fasting plasma glucose, among both the overall population (N = 878; -1.27%-points [95% CI: -1.36; -1.19]; p < 0.0001, and -1.61 mmol/L [95% CI: -1.81; -1.41]; p < 0.0001, respectively), and in subgroups switching from OADs only, or basal, or premix insulins ± OADs. The mean total DTSQ score increased from 26.4 (baseline) to 31.6 (end-of-study). No significant, or unexpected tolerability, or safety issues were observed. Significant reductions were observed in incidence rates of non-severe (rate ratio 0.37 [95% CI: 0.24; 0.59]; p < 0.0001) and nocturnal non-severe (rate ratio 0.45 [95% CI: 0.21; 0.94]; p = 0.0326) hypoglycaemic episodes. CONCLUSIONS In a broad, real-world Chinese population of adults with T2D, initiating or switching to IDegAsp was associated with improved glycaemic control and lower rates of hypoglycaemia. The use of IDegAsp could be an effective treatment option for those with suboptimal glycaemic control or therapeutic inertia.
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Affiliation(s)
- Lixin Guo
- Department of EndocrinologyBeijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical SciencesBeijingChina
| | - Liming Chen
- Chu Hsien‐I Memorial Hospital & Tianjin Institute of EndocrinologyTianjin Medical UniversityTianjinChina
| | - Fan Zhao
- The People's Hospital of JiangmenJiangmenChina
| | | | | | - Kun Wang
- Endocrinology DepartmentJiangning Hospital affiliated to Nanjing Medical UniversityNanjingChina
| | - Xing Zhong
- Novo Nordisk (Shanghai) Pharma Trading Co. LtdShanghaiChina
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Yang N, Lv L, Han SM, He LY, Li ZY, Yang YC, Ping F, Xu LL, Li W, Zhang HB, Li YX. Efficacy, safety and treatment satisfaction of transition to a regimen of insulin degludec/aspart: A pilot study. World J Diabetes 2025; 16:95209. [PMID: 39817213 PMCID: PMC11718447 DOI: 10.4239/wjd.v16.i1.95209] [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: 04/04/2024] [Revised: 09/19/2024] [Accepted: 10/08/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin deglu-dec/aspart (IDegAsp) therapy, with insufficient data from the Chinese popu-lation. AIM To demonstrate the efficacy, safety, and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus (T2DM). METHODS In this 12-week open-label, non-randomized, single-center, pilot study, patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp. Insulin doses, hemoglobin A1c (HbA1c) levels, fasting blood glucose (FBG), hypoglycemic events, a Diabetes Treatment Satisfaction Questionnaire, and other parameters were assessed at baseline and 12-weeks. RESULTS This study included 21 participants. A marked enhancement was observed in the FBG level (P = 0.02), daily total insulin dose (P = 0.03), and overall diabetes treatment satisfaction (P < 0.01) in the participants who switched to IDegAsp. There was a decrease in HbA1c levels (7.6 ± 1.1 vs 7.4 ± 0.9, P = 0.31) and the frequency of hypoglycemic events of those who switched to IDegAsp decreased, however, there was no statistically significant difference. CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes, particularly FBG levels, daily cumulative insulin dose, and overall satisfaction with diabetes treatment.
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Affiliation(s)
- Na Yang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Lu Lv
- Department of Allergy, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100730, China
| | - Shu-Meng Han
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Li-Yun He
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Zi-Yi Li
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yu-Cheng Yang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Fan Ping
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Ling-Ling Xu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Wei Li
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hua-Bing Zhang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yu-Xiu Li
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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Fulcher GR, Cohen ND, Davies K, d'Emden M, Glastras SJ, Mah PM, McCallum RW, Moses R, Thong KY, Roberts A. Initiating or switching to insulin degludec/insulin aspart in a real-world population of adults with type 2 diabetes in Australia: results from a prospective, non-interventional study. Intern Med J 2024; 54:1626-1633. [PMID: 39171857 DOI: 10.1111/imj.16492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 07/25/2024] [Indexed: 08/23/2024]
Abstract
BACKGROUND Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec and insulin aspart for the treatment of people with diabetes and suboptimal glycaemic control. Few real-world studies of IDegAsp treatment have been conducted. Here, we report results from the Australian cohort of the global ARISE study of real-world IDegAsp use. AIMS To investigate glycaemic control and other clinical outcomes in people with type 2 diabetes (T2D) treated with IDegAsp in a real-world setting in Australia. METHODS A total of 183 adults with T2D initiating or switching to IDegAsp in the Australian cohort of the open-label, non-interventional ARISE study were followed for 26-36 weeks from August 2019 to December 2020. RESULTS IDegAsp was associated with significant reductions from baseline to end of study (EOS) in mean glycated haemoglobin (estimated change -0.8% (95% confidence interval (CI): -1.05 to -0.56; P < 0.0001)), fasting plasma glucose (-1.6 mmol/L (95% CI: -2.49 to -0.63; P = 0.0017)) and body weight (-2.6 kg (95% CI: -3.68 to -1.55; P < 0.0001)). In insulin-experienced patients, the mean total daily insulin dose did not change significantly (estimated change from baseline to EOS 3.8 (95% CI: -3.70 to 11.21; P = 0.3202)). The proportion of patients experiencing hypoglycaemia numerically decreased during the study (non-severe: 14.2-10.9%; nocturnal non-severe: 4.9-2.2%; and severe: 2.2-0%). CONCLUSIONS Initiating or switching to IDegAsp in a real-world population of people with T2D in Australia was associated with significant improvements in glycaemic control and body weight, and numerically lower levels of hypoglycaemia compared with baseline.
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Affiliation(s)
- Gregory R Fulcher
- Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia
| | - Neale D Cohen
- Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
| | | | - Michael d'Emden
- Department of Endocrinology and Diabetes, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
| | - Sarah J Glastras
- Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, New South Wales, Australia
- Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia
- Kolling Institute of Medical Research, Sydney, New South Wales, Australia
| | - Peak M Mah
- Department of Diabetes and Endocrinology, Lyell McEwin Hospital, Adelaide, South Australia, Australia
| | - Roland W McCallum
- Diabetes and Endocrine Services, Royal Hobart Hospital, Hobart, Tasmania, Australia
| | - Robert Moses
- Clinical Trial and Research Unit, Illawarra Shoalhaven Local Health District, Wollongong, New South Wales, Australia
| | - Ken Y Thong
- Department of Diabetes and Endocrinology, Rockingham General Hospital, Perth, Western Australia, Australia
| | - Anthony Roberts
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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Kang S, Ahn YB, Oh TK, Lee WY, Chun SW, Bae B, Dahaoui A, Jeong JS, Jung S, Jang HC. Efficacy and Safety of IDegAsp in a Real-World Korean Population with Type 2 Diabetes Mellitus. Diabetes Metab J 2024; 48:929-936. [PMID: 38410023 PMCID: PMC11449825 DOI: 10.4093/dmj.2023.0297] [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: 08/24/2023] [Accepted: 11/22/2023] [Indexed: 02/28/2024] Open
Abstract
BACKGRUOUND This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp. METHODS This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106). RESULTS In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. -0.51%, P<0.001; 5.21 mg/dL vs. -23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods. CONCLUSION In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.
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Affiliation(s)
- Shinae Kang
- Division of Endocrinology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yu-Bae Ahn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Tae Keun Oh
- Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Won-Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Wan Chun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Boram Bae
- Novo Nordisk Pharma Korea Limited, Seoul, Korea
| | - Amine Dahaoui
- Novo Nordisk Region Asia Pacific, Dubai, United Arab Emirates
| | | | - Sungeun Jung
- Novo Nordisk Region Asia Pacific, Dubai, United Arab Emirates
| | - Hak Chul Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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Walt JR, Loughran J, Fourlanos S, Barmanray RD, Zhu J, Varadarajan S, Kyi M. Glycaemic outcomes in hospital with IDegAsp versus BIAsp30 premixed insulins. Intern Med J 2024; 54:1329-1336. [PMID: 38578058 DOI: 10.1111/imj.16391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Accepted: 03/11/2024] [Indexed: 04/06/2024]
Abstract
BACKGROUND AND AIMS IDegAsp (Ryzodeg 70/30), a unique premixed formulation of long-acting insulin degludec and rapid-acting insulin aspart, is increasing in use. Management of IDegAsp during hospitalisation is challenging because of degludec's ultra-long duration of action. We investigated inpatient glycaemia in patients treated with IDegAsp compared to biphasic insulin aspart (BIAsp30; Novomix30). METHODS We performed a retrospective observational study at two hospitals assessing inpatients with type 2 diabetes treated with IDegAsp or BIAsp30 prior to and during hospital admission. Standard inpatient glycaemic outcomes were analysed based on capillary blood glucose (BG) measurements. RESULTS We assessed 88 individuals treated with IDegAsp and 88 HbA1c-matched individuals treated with BIAsp30. Patient characteristics, including insulin dose at admission, were well matched, but the IDegAsp group had less frequent twice-daily insulin dosing than the BIAsp30 group (49% vs 87%, P < 0.001). Patient-days with BG <4 mmol/L were not different (10.6% vs 9.9%, P = 0.7); however, the IDegAsp group had a higher patient-day mean BG (10.4 (SD 3.4) vs 10.0 (3.4) mmol/L, P < 0.001), and more patient-days with mean BG >10 mmol/L (48% vs 38%, P < 0.001) compared to the BIAsp30 group. Glucose was higher in the IDegAsp group in the evening (4 PM to midnight) (11.6 (SD 4.0) vs 10.9 (4.6) mmol/L, P = 0.004), but not different at other times during the day. CONCLUSIONS Inpatients treated with IDegAsp compared to BIAsp30 had similar hypoglycaemia incidence, but higher hyperglycaemia incidence, potentially related to less frequent twice-daily dosing. With the increasing use of IDegAsp in the community, development of hospital management guidelines for this insulin formulation is needed.
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Affiliation(s)
- Joshua R Walt
- Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Royal Melbourne Clinical School, The University of Melbourne, Melbourne, Victoria, Australia
| | - Julie Loughran
- Endocrinology Unit, Northern Hospital, Epping, Victoria, Australia
| | - Spiros Fourlanos
- Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Medicine at Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
- Australian Centre for Accelerating Diabetes Innovations, The University of Melbourne, Parkville, Victoria, Australia
| | - Rahul D Barmanray
- Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Department of Medicine at Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
- Australian Centre for Accelerating Diabetes Innovations, The University of Melbourne, Parkville, Victoria, Australia
| | - Jasmine Zhu
- Endocrinology Unit, Northern Hospital, Epping, Victoria, Australia
| | | | - Mervyn Kyi
- Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
- Endocrinology Unit, Northern Hospital, Epping, Victoria, Australia
- Department of Medicine at Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia
- Australian Centre for Accelerating Diabetes Innovations, The University of Melbourne, Parkville, Victoria, Australia
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Lechleitner M, Roden M, Weitgasser R, Ludvik B, Fasching P, Hoppichler F, Kautzky-Willer A, Schernthaner G, Prager R, Kaser S, Wascher TC. [Injection therapy of diabetes]. Wien Klin Wochenschr 2023; 135:45-52. [PMID: 37101024 PMCID: PMC10133050 DOI: 10.1007/s00508-023-02171-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/22/2023] [Indexed: 04/28/2023]
Abstract
The present article is a recommendation of the Austrian Diabetes Association for the practical use of injection therapy (GLP1-receptor agonists and insulin) in type 2 diabetes.
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Affiliation(s)
- Monika Lechleitner
- Avomed-Arbeitskreis für Vorsorgemedizin und Gesundheitsförderung in Tirol, Innsbruck, Österreich
| | - Michael Roden
- Klinik für Endokrinologie und Diabetologie, Medizinische Fakultät, Heinrich-Heine-Universität, Düsseldorf, Deutschland
- Institut für Klinische Diabetologie, Deutsches Diabetes-Zentrum (DDZ), Leibniz-Zentrum für Diabetesforschung, Düsseldorf, Deutschland
- Deutsches Zentrum für Diabetesforschung (DZD e. V.), München-Neuherberg, Deutschland
| | - Raimund Weitgasser
- Abteilung für Innere Medizin, Privatklinik Wehrle-Diakonissen, Salzburg, Österreich
- Universitätsklinik für Innere Medizin I, LKH Salzburg - Universitätsklinikum der Paracelsus Medizinischen Privatuniversität, Salzburg, Österreich
| | - Bernhard Ludvik
- Medizinische Abteilung mit Diabetologie, Endokrinologie und Nephrologie, Klinik Landstraße, Wien, Österreich
| | - Peter Fasching
- Medizinische Abteilung für Endokrinologie, Rheumatologie und Akutgeriatrie, Wilhelminenspital der Stadt Wien, Wien, Österreich
| | - Friedrich Hoppichler
- Abteilung für Innere Medizin, Krankenhaus der Barmherzigen Brüder Salzburg, Salzburg, Österreich
| | - Alexandra Kautzky-Willer
- Gender Medicine Unit, Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Spitalgasse 23, 1090, Wien, Österreich.
| | - Guntram Schernthaner
- Department of Internal Medicine II, Medizinische Universität Wien, Wien, Österreich
| | - Rudolf Prager
- Stoffwechselzentrum im Rudolfinerhaus, Rudolfinerhaus Privatklinik, Wien, Österreich
| | - Susanne Kaser
- Department für Innere Medizin 1, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - T C Wascher
- Medizinische Abteilung, Hanusch-Krankenhaus, Wien, Österreich
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Luo Q, Zhou L, Zhou N, Hu M. Cost-effectiveness of insulin degludec/insulin aspart versus biphasic insulin aspart in Chinese population with type 2 diabetes. Front Public Health 2022; 10:1016937. [PMID: 36330105 PMCID: PMC9623119 DOI: 10.3389/fpubh.2022.1016937] [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: 08/11/2022] [Accepted: 10/03/2022] [Indexed: 01/28/2023] Open
Abstract
Objective To evaluate the long-term cost effectiveness of insulin degludec/insulin aspart (IDegAsp) vs. biphasic insulin aspart 30 (BIAsp 30) for the treatment of people with type 2 diabetes mellitus (T2DM) inadequately managed on basal insulin in China. Methods The CORE (the Center for Outcomes Research) Diabetes Model, which has been published and verified, was used to simulate disease progression and calculate the total direct medical costs, life years (LYs) and quality-adjusted life years (QALYs) over 30 years, from the perspective of Chinese healthcare system. The patient demographic information and clinical data needed for the model were gathered from a phase III treat-to-target clinical trial (NCT02762578) and other Chinese cohort studies. Medical costs on treating diabetes were calculated based on clinical trial and local sources. The diabetes management and complications costs were derived from published literature. A discounting rate of 5% was applied to both health and cost outcomes. And one-way and probabilistic sensitivity analyses were carried out to test the reliability of the results. Results Compared with BIAsp 30, treatment with IDegAsp was associated with an incremental benefit of 0.001 LYs (12.439 vs. 12.438) and 0.280 QALYs (9.522 vs. 9.242) over a 30-year time horizon, and increased CNY (Chinese Yuan) 3,888 (390,152 vs. 386,264) for total costs. IDegAsp was cost-effective vs. BIAsp 30 therapy with an incremental cost-effectiveness ratio of CNY 13,886 per QALY gained. Results were robust across a range of sensitivity analyses. Conclusion Compared with BIAsp 30, IDegAsp was a cost-effective treatment option for people with T2DM with inadequate glycemic management on basal insulin in China.
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Chawla M, Chawla P, Saboo B, Chawla R, Gangopadhyay KK, Kalra S, Aravind S, Sinha B, Shah T, Kesavadev J, Rajput R. Scientific advisory on nocturnal hypoglycemia in insulin-treated patients with diabetes: Recommendations from Indian experts. Diabetes Metab Syndr 2022; 16:102587. [PMID: 36055167 DOI: 10.1016/j.dsx.2022.102587] [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: 02/07/2022] [Revised: 07/21/2022] [Accepted: 07/23/2022] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Insulin is one of the commonly prescribed glucose lowering agents in diabetes. Hypoglycemia is the most common complication, and severe hypoglycemia is the most serious complication of insulin therapy. Almost half of all severe hypoglycemia episodes (HEs) occur at night. However, patients are often unaware of their nocturnal hypoglycaemia (NH) risk. Additionally, both healthcare professionals and patients find it difficult to manage NH. The purpose of this expert group meeting is to improve NH awareness and provide guidance for the physicians to recognize and manage NH. METHOD The panel of experts in an e-board deliberated extensively upon the available literature and guidelines on hypoglycemia and NH discussed the consensus on definition, detection, reporting, monitoring, treatment, and optimization of therapy in NH. RESULT & Conclusion: Though there are many guidelines on the management of HEs in patients with diabetes, very few touch the topic of NH. This scientific advisory on management of NH in insulin treated patients with diabetes is formulated to address this gap in understanding regarding management of NH. The experts provide recommendations for the nocturnal window, defining NH based on blood glucose values, recognition, prevention and management of NH.
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Affiliation(s)
- M Chawla
- Lina Diabetes Care Centre, Mumbai, India.
| | - P Chawla
- Consultant Diabetologist and Director of Clinical Research, Lina Diabetes Care and Mumbai Diabetes Research Centre, Mumbai, India
| | - B Saboo
- Dept of Endocrinology, Dia Care, Ahmedabad, Gujrat, India
| | - R Chawla
- North Delhi Diabetes Centre, Rohini, New Delhi, India
| | - K K Gangopadhyay
- Consultant in Endocrinology, CK Birla Hospitals, Peerless Hospital, India
| | - S Kalra
- Department of Endocrinology, Bharti Hospital, Karnal, India
| | | | - B Sinha
- AMRI and Fortis Hospitals, Kolkata, India
| | - T Shah
- Director and Diabetologist Iva Diabetes Care Centre Mumbai, Sl Raheja Fortis Hospital, Mumbai, India
| | - J Kesavadev
- Jothydev's Diabetes and Research Center, Kerala, India
| | - R Rajput
- Department of Endocrinology, PGIMS, Rohtak, Haryana, India
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Oner H, Gunhan HG, Gogas Yavuz D. Intensification of Insulin Treatment With Insulin Degludec/Aspart in Type 2 Diabetic Patients: A 2-Year Real-World Experience. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2022; 3:783277. [PMID: 36992737 PMCID: PMC10012153 DOI: 10.3389/fcdhc.2022.783277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 05/09/2022] [Indexed: 06/19/2023]
Abstract
AIM To evaluate the effects of insulin degludec/insulin aspart (IDegAsp) coformulation as an intensification of insulin treatment for glycemic control in patients with type 2 diabetes (T2D) in a long term real-world clinical setting. MATERIALS AND METHODS This retrospective non-interventional study, included 210 patients with T2D who to IDegAsp coformulation from prior insulin treatment in a tertiary endocrinology center between September 2017 and December 2019. The baseline data was taken as the index date and defined as the first IDegAsp prescription claim. Previous insulin treatment modalities, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight were recorded, respectively at the 3rd, 6th, 12th, and 24th months of the IDegAsp treatment. RESULTS Out of the total 210 patients, 166 patients under insulin treatment switched to twice-daily IDegAsp treatment, 35 patients switched to once daily IDegAsp and twice premeal short-acting insulin regimen as a modified basal-bolus (BB) treatment, and nine patients commenced with once-daily IDegAsp treatment. HbA1c decreased from 9.2% ± 1.9% to 8.2% ± 1.6% in 6 months, 8.2% ± 1.7% in the first year, and 8.1% ± 1.6% in the second year of the therapy (p< 0.001). FPG decreased from 209.0 ± 85.0 mg/dL to 147.0 ± 62.6 mg/dL in the second year (p< 0.001). The required total daily dose of insulin increased in the second year of IDegAsp treatment compared to baseline. However, there was a borderline significance increase in IDegAsp requirement for the whole group at the two-year follow-up (p = 0.05). Patients who were administered twice daily IDegAsp injections required more total insulin in the first and second years due to added premeal short-acting insulin injections (p < 0.05). The frequency of patients with HbA1c < 7% was 31.8% in first year and 35.8% in second year under IDegAsp treatment.Insulin dose was de-escalated in 28.5% of the patients under BB treatment, while 15% under twice-daily IDegAsp required increased BB treatment. CONCLUSION Intensification of insulin treatment with IDegAsp coformulation improved glycemic control in patients with T2D. The total daily insulin requirement increased but the IDegAsp requirement lightly increased at the two-year follow-up. Patients under BB treatment required de-escalation of insulin treatment.
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Affiliation(s)
- Hatice Oner
- Department of Endocrinology and Metabolism, Marmara University School of Medicine, Istanbul, Turkey
| | - Hatice Gizem Gunhan
- Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey
| | - Dilek Gogas Yavuz
- Department of Endocrinology and Metabolism, Marmara University School of Medicine, Istanbul, Turkey
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Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes: A Real-World, Prospective, Non-interventional Study Across Six Countries. Adv Ther 2022; 39:3735-3748. [PMID: 35752730 PMCID: PMC9244059 DOI: 10.1007/s12325-022-02212-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 05/31/2022] [Indexed: 11/17/2022]
Abstract
Introduction Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (a basal insulin) and insulin aspart (a prandial insulin). The aim of this study was to investigate clinical outcomes in people with type 2 diabetes (T2D) after initiating IDegAsp treatment in a real-world setting. Methods This 26-week, open-label, non-interventional study was conducted in Australia, India, Malaysia, Philippines, Saudi Arabia, and South Africa. Data were obtained from 1102 adults with T2D initiating or switching to IDegAsp from antidiabetic treatments (including oral antidiabetic drugs, basal insulin, basal–bolus insulin, premix insulin, and glucagon-like peptide 1 receptor agonist) per local clinical practice. Results Compared with baseline, there was significant improvement in HbA1c at end of study (EOS, first visit within weeks 26–36; estimated change − 1.4% [95% CI − 1.51; − 1.29]; P < 0.0001 [primary outcome]). From baseline to EOS, there were significant reductions in fasting plasma glucose (− 2.7 mmol/L [95% CI − 2.98; − 2.46]; P < 0.0001), body weight (− 1.0 kg [95% CI − 1.51; − 0.52]; P < 0.0001), and basal insulin dose in insulin-experienced participants (− 2.3 units [95% CI − 3.51; − 1.01]; P < 0.001). The incidence rates of non-severe (overall and nocturnal) and severe hypoglycaemia decreased significantly (P < 0.001) between the period before baseline and before EOS. Conclusion In adults with T2D, initiating or switching to IDegAsp from previous antidiabetic treatment was associated with improved glycaemic control, lower basal insulin dose (in insulin-experienced participants), and lower rates of hypoglycaemia. Trial Registration Clinical trial registration NCT04042441. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-022-02212-3.
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12
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Edina BC, Tandaju JR, Wiyono L. Efficacy and Safety of Insulin Degludec/Insulin Aspart (IDegAsp) in Type 2 Diabetes: Systematic Review and Meta-Analysis. Cureus 2022; 14:e25612. [PMID: 35784980 PMCID: PMC9249063 DOI: 10.7759/cureus.25612] [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] [Accepted: 06/02/2022] [Indexed: 11/30/2022] Open
Abstract
Type 2 diabetes mellitus is a prevalent metabolic disease requiring tight glycemic control of basal and postprandial glucose levels. Treatment intensification using separate basal and bolus injections increased the number of injections and reduced cost-effectivity, leading to decreased compliance and failure of glycemic control. Insulin Degludec/Insulin Aspart (IDegAsp), a novel premix of basal and bolus insulin, is one of the potential treatments for reducing the number of injections. However, its efficacy and safety have not been reviewed clearly. Therefore, this systematic review aims to compare the efficacy and safety of IDegAsp with standard basal and basal plus bolus insulin regimens. A systematic review of four databases (Pubmed, Scopus, Science Direct, and Proquest) was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Search results were screened by eligibility criteria and critically appraised by the Oxford Centre for Evidence-Based Medicine (CEBM) tool and the Cochrane risk-of-bias assessment tool. Meta-Analysis was done using Review Manager to obtain cumulative outcomes from hemoglobin A1C (HbA1C) changes, hypoglycemia incidents, and weight gain from all studies. Out of 132 search results, 10 studies were reviewed. IDegAsp once-daily administration was proven beneficial in reducing HbA1c levels and nocturnal hypoglycemia incidences, while IDegAsp twice-daily administration was proven beneficial in lowering hypoglycemia incidence and nocturnal hypoglycemia incidence. IDegAsp yielded better glycemic index results and lowered hypoglycemic incidents in the meta-analysis. Thus, it is concluded that IDegAsp once daily with stepwise titration on the largest meal of the day achieved most benefits with minimal risks.
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Affiliation(s)
- Brenda C Edina
- Faculty of Medicine, Universitas Indonesia, Jakarta, IDN
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Yang W, Akhtar S, Franek E, Haluzík M, Hirose T, Kalyanam B, Kar S, Wu T, Gogas Yavuz D, Unnikrishnan AG. Postprandial Glucose Excursions in Asian Versus Non-Asian Patients with Type 2 Diabetes: A Post Hoc Analysis of Baseline Data from Phase 3 Randomised Controlled Trials of IDegAsp. Diabetes Ther 2022; 13:311-323. [PMID: 35044568 PMCID: PMC8873325 DOI: 10.1007/s13300-021-01196-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/22/2021] [Indexed: 11/03/2022] Open
Abstract
INTRODUCTION Increased postprandial glucose (PPG) is associated with high glycated haemoglobin levels and is an independent risk factor for cardiovascular diseases. The aim of this study was to compare PPG increments in Asian versus non-Asian adults with type 2 diabetes (T2D), who were insulin-naïve or insulin-experienced, from the phase 3 insulin degludec/insulin aspart (IDegAsp) clinical trials. METHODS This was a post hoc analysis of data from 13 phase 3, randomised, parallel-group, open-label IDegAsp trials in patients with T2D. The pooled baseline clinical data were analysed for insulin-naïve and insulin-experienced groups; and each group was split into subgroups of Asian and non-Asian patients, respectively, and analysed accordingly. Baseline self-monitored blood glucose (SMBG) values at breakfast, lunch and the evening meal (before and 90 min after each meal) were used to assess PPG increments. The estimated differences in baseline SMBG increment between the Asian and non-Asian subgroups were analysed. RESULTS Clinical data from 4750 participants (insulin-naïve, n = 1495; insulin-experienced, n = 3255) were evaluated. In the insulin-naïve group, the postprandial SMBG increment was significantly greater in the Asian versus the non-Asian subgroup at breakfast (estimated difference 28.67 mg/dL, 95% confidence interval [CI] 18.35, 38.99; p < 0.0001), lunch (17.34 mg/dL, 95% CI 6.47, 28.21; p = 0.0018) and the evening meal (16.19 mg/dL, 95% CI 5.04, 27.34; p = 0.0045). In the insulin-experienced group, the postprandial SMBG increment was significantly greater in the Asian versus non-Asian subgroup at breakfast (estimated difference 13.81 mg/dL, 95% CI 9.19, 18.44; p < 0.0001) and lunch (29.18 mg/dL, 95% CI 24.22, 34.14; p < 0.0001), but not significantly different at the evening meal. CONCLUSION In this post hoc analysis, baseline PPG increments were significantly greater in Asian participants with T2D than in their non-Asian counterparts at all mealtimes, with the exception of the evening meal in insulin-experienced participants. Asian adults with T2D may benefit from the use of regimens that control PPG excursions. CLINICAL TRIAL NUMBERS NCT02762578, NCT01814137, NCT01513590, NCT01009580, NCT01713530, NCT02648217, NCT01045447, NCT01365507, NCT01045707, NCT01272193, NCT01059812, NCT01680341, NCT02906917.
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Affiliation(s)
- Wenying Yang
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, 100029, China.
| | - Shahid Akhtar
- Clinical, Medical and Regulatory Department, Novo Nordisk Pharma Gulf FZ-LLC, Dubai, United Arab Emirates
| | | | - Martin Haluzík
- Institute for Clinical and Experimental Medicine and Charles University, Prague, Czech Republic
| | | | | | - Soumitra Kar
- Novo Nordisk Service Centre India Private Ltd., Bangalore, India
| | - Ted Wu
- Diabetes Centre, Royal Prince Alfred Hospital, Sydney, Australia
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Katabami T, Eriksen KT, Yamamoto Y, Ishigaki Y. Long-Term Safety and Clinical Outcomes with Insulin Degludec/Insulin Aspart Treatment in Japanese Patients with Diabetes: A Real-World, Prospective, Observational Study. Adv Ther 2022; 39:544-561. [PMID: 34800283 PMCID: PMC8799571 DOI: 10.1007/s12325-021-01978-2] [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: 03/16/2021] [Accepted: 10/21/2021] [Indexed: 11/21/2022]
Abstract
Introduction Insulin degludec/insulin aspart (IDegAsp) provides effective glycaemic control with an acceptable safety profile in Japanese patients with diabetes in randomised clinical trials. This post-marketing surveillance study assessed long-term safety and clinical outcomes with IDegAsp in a Japanese real-world setting. Methods Multicentre, prospective, observational, open-label, single-arm study of Japanese patients with diabetes requiring insulin therapy, who had switched to IDegAsp at their treating physician’s discretion in clinical practice. One year after initiating IDegAsp, incidence of adverse events (AEs [primary endpoint]), serious AEs, adverse drug reactions (ADRs), and severe hypoglycaemia (secondary safety endpoints) were assessed in the safety analysis set (SAS). Secondary effectiveness endpoints were change from baseline in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) in the effectiveness analysis set (EAS). Results Overall, 1321 patients were included (SAS, n = 1321; EAS, n = 1285); 4.2% with type 1 diabetes, 95.2% with type 2 diabetes, 0.7% with other/unknown diabetes type. In total, 204 AEs were reported in 132 patients (10.0% of the SAS), at a rate [95% confidence interval (CI)] of 16.2 events/100 patient-years of exposure (PYE) [14.0; 18.4]. By preferred term, ‘hypoglycaemia’ was the most frequent AE (45 events in 31 patients [2.3%]; rate [95% CI] 3.6 events/100 PYE [2.5; 4.6]). Serious AEs occurred in 4.2% of patients (rate [95% CI] 5.7 events/100 PYE [4.4; 7.0]), and ADRs in 3.1% (rate [95% CI] 4.6 reactions/100 PYE [3.4; 5.8]). Six events of severe hypoglycaemia were reported in five patients (0.4%; rate [95% CI] 0.5 events/100 PYE [0.1; 0.9]). Change from baseline to 1 year was − 0.51% and − 32.1 mg/dL for HbA1c and FPG, respectively (P < 0.0001 for both). Conclusion In Japanese patients with diabetes, initiation of IDegAsp in real-world clinical practice was well tolerated, with no new safety signals, and associated with improved glycaemic control after 1 year.
Trial Registration ClinicalTrials.gov identifier, NCT02821052. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01978-2.
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15
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Kovil R. Comparing time to intensification between insulin degludec/insulin aspart and insulin glargine: A single-center experience from India. JOURNAL OF DIABETOLOGY 2022. [DOI: 10.4103/jod.jod_20_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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16
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Jang HN, Yang YS, Oh TJ, Koo BK, Lee SO, Park KS, Jang HC, Jung HS. Low fasting glucose-to-estimated average glucose ratio was associated with superior response to insulin degludec/aspart compared with basal insulin in patients with type 2 diabetes. J Diabetes Investig 2022; 13:85-93. [PMID: 34291584 PMCID: PMC8756314 DOI: 10.1111/jdi.13634] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 07/11/2021] [Accepted: 07/20/2021] [Indexed: 01/21/2023] Open
Abstract
AIMS/INTRODUCTION The benefits of once-daily insulin degludec/aspart (IDegAsp) compared with basal insulin in type 2 diabetes patients have not been established. MATERIALS AND METHODS This was a retrospective observational study. From a basal insulin cohort from three referral hospitals, patients were enrolled who initiated once-daily IDegAsp. A control group maintaining basal insulin was selected by propensity score matching. Glycated hemoglobin (HbA1c) changes over a period of 6 months and associated clinical factors were evaluated. RESULTS The IDegAsp group and the control group comprised of 87 patients, respectively. Baseline HbA1c was comparable between the two groups (8.7 ± 0.9 vs 8.6 ± 0.9%, mean and standard deviation). After 6 months with matched insulin doses, HbA1c in the IDegAsp group was lower than that in the control group (8.1 ± 1.0 vs 8.4 ± 1.1%, P = 0.029). Among baseline variables, fasting plasma glucose (FPG) and fasting C-peptide in the IDegAsp were lower than that in the control (FPG 124.2 ± 38.4 vs 148.0 ± 50.6 mg/dL, P < 0.001). Considering that the lower FPG despite the comparable HbA1c could be related with the efficacy of IDegAsp, subgroup analysis was carried out according to a ratio of FPG-to-estimated average glucose, which is calculated from HbA1c. When compared with each control group, the superiority of IDegAsp in the reduction of HbA1c was significant only in the patients with a lower FPG-to-estimated average glucose ratio (0.49 ± 0.09), but not in those with a higher FPG-to-estimated average glucose ratio (0.79 ± 0.20). CONCLUSIONS We observed that IDegAsp was more effective than basal insulin in patients with an FPG lower than predicted by HbA1c, which might be related with insulin deficiency and postprandial hyperglycemia in patients on basal insulin therapy.
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Affiliation(s)
- Han Na Jang
- Division of Endocrinology and Metabolism, Department of Internal MedicineSeoul National University HospitalSeoulKorea
| | - Ye Seul Yang
- Division of Endocrinology and Metabolism, Department of Internal MedicineSeoul National University HospitalSeoulKorea
- Present address:
Division of Endocrinology and Metabolism, Department of Internal MedicineUijeongbu St. Mary’s HospitalUijeongbuKorea
| | - Tae Jung Oh
- Division of Endocrinology and Metabolism, Department of Internal MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Bo Kyung Koo
- Division of Endocrinology and Metabolism, Department of Internal MedicineSeoul Metropolitan Government Seoul National University Boramae Medical CenterSeoulKorea
| | - Seong Ok Lee
- Division of Endocrinology and Metabolism, Department of Internal MedicineSeoul National University HospitalSeoulKorea
| | - Kyong Soo Park
- Division of Endocrinology and Metabolism, Department of Internal MedicineSeoul National University HospitalSeoulKorea
| | - Hak Chul Jang
- Division of Endocrinology and Metabolism, Department of Internal MedicineSeoul National University Bundang HospitalSeongnamKorea
| | - Hye Seung Jung
- Division of Endocrinology and Metabolism, Department of Internal MedicineSeoul National University HospitalSeoulKorea
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Fulcher GR, Jarlov H, Piltoft JS, Singh KP, Liu L, Mohamed M, Nicodemus NA, Al-Jaser SJ, Kok A. ARISE-a prospective, non-interventional, single-arm study assessing clinical parameters associated with the use of insulin degludec/insulin aspart in patients with type 2 diabetes in real-world settings: rationale and design. Endocrine 2021; 74:530-537. [PMID: 34637072 PMCID: PMC8506473 DOI: 10.1007/s12020-021-02887-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Accepted: 09/16/2021] [Indexed: 11/28/2022]
Abstract
PURPOSE IDegAsp, a co-formulation of long-acting basal (insulin degludec) and rapid-acting bolus (insulin aspart) insulin, provides separate prandial and basal glucose-lowering effects with relatively low risk of hypoglycaemia. Its efficacy and safety have been investigated in a large clinical trial programme (BOOST). We present the rationale and design of the ARISE study, which aims to assess glycaemic control and other clinical parameters associated with IDegAsp use in real world. METHODS ARISE is a ~26-wk-long, prospective, non-interventional, single-arm study of patients with type 2 diabetes (T2D) initiating IDegAsp treatment. Approximately 1112 patients with T2D aged ≥18 years previously on anti-hyperglycaemic drugs except IDegAsp will be enroled across six countries from 15 Aug 2019 to 12 Nov 2020. IDegAsp treatment will be initiated at the physicians' discretion and as per the local label. Key exclusion criteria include previous participation, or previous IDegAsp treatment. The primary and secondary endpoints are change in HbA1c from baseline (wk 0) to study end (wk 26-36) and the proportion of patients achieving the target HbA1c level of <7% at the study end, respectively. A mixed model for repeated measurements will analyse the primary endpoint. CONCLUSION Between-country differences in the prescription patterns of glucose-lowering agents in people with T2D warrant examination of their clinical use in different geographical settings. The ARISE study is designed to assess the clinical use of IDegAsp from real world in six different countries. Findings from the ARISE study will supplement those of previous randomised controlled studies by establishing real-world evidence of IDegAsp use in the participating countries. TRIAL REGISTRATION ClinicalTrials.gov, NCT04042441. Registered 02 August 2014, https://clinicaltrials.gov/ct2/show/NCT04042441.
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Affiliation(s)
- Gregory R Fulcher
- Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, Sydney, NSW, Australia.
- Northern Clinical School, University of Sydney, Sydney, NSW, Australia.
| | | | | | - Kiran Pal Singh
- Department of Endocrinology, Fortis Hospital, Mohali, Punjab, India
| | - Lei Liu
- Novo Nordisk A/S, Søborg, Denmark
| | - Mafauzy Mohamed
- Department of Medicine, Hospital Universiti Sains Malaysia, Kota Bharu, Kelantan, Malaysia
| | - Nemencio Almare Nicodemus
- Department of Biochemistry and Molecular Biology, University of the Philippines-College of Medicine, Manila, Philippines
| | - Saleh Jaser Al-Jaser
- Department of Internal Medicine, Specialised Medical Center, Riyadh, Saudi Arabia
| | - Adri Kok
- Union and Clinton Hospitals in Alberton, Gauteng, South Africa
- Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa
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Mannucci E, Caiulo C, Naletto L, Madama G, Monami M. Efficacy and safety of different basal and prandial insulin analogues for the treatment of type 2 diabetes: a network meta-analysis of randomized controlled trials. Endocrine 2021; 74:508-517. [PMID: 34599695 DOI: 10.1007/s12020-021-02889-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 09/17/2021] [Indexed: 11/26/2022]
Abstract
AIM The aim of the present network meta-analysis is to assess the efficacy and safety across different long and short-acting analogs for the treatment of type 2 diabetes. METHODS A PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases search (20th May, 2020) for all trials with a duration ≥24 weeks comparing an analogue with another or human insulin was performed. Indirect comparisons were performed by NMA choosing glargine U100 and human regular insulin, as the reference for long- and short-acting analogues, respectively. Primary endpoints were HbA1c at 24, 52, and 104 weeks. The weighted difference in means (WDM) and Mantel-Haenzel Odds Ratio [MH-OR] with 95% Confidence Intervals (CI) were calculated for categorical and continuous variables, respectively. RESULTS Fifty trials (n = 43) and 7 for basal and prandial analogues, respectively, enrolling 25,554 and 3184 patients with type 2 and 1 diabetes, respectively, were included. At NMA, detemir was less effective than glargine U-100 at 52 weeks. A significant reduction of 24-week HbA1c (WMD [IC]: -0.10 [-0.17, -0.03]%); and risk of total (MH-OR [IC]: 0.80 [0.70, 0.91]), and nocturnal hypoglycemia (MH-OR [IC]: 0.57 [0.45, 0.73]) was observed for basal analogues versus NPH insulin. At NMA, glargine U300 and degludec were associated with a significant reduction in the risk of nocturnal hypoglycemia. No significant differences across different short-acting insulin were observed. CONCLUSIONS This paper supports the use of long-acting analogues, rather than NPH insulin, as basal insulin for the treatment of type 2 diabetes, without any preferences for any individual long-acting analogue over the others. The evidence on short acting analogues is limited.
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Affiliation(s)
- Edoardo Mannucci
- Diabetology, Careggi Hospital, University of Florence, Florence, Italy
- University of Florence, Florence, Italy
| | | | | | | | - Matteo Monami
- Diabetology, Careggi Hospital, University of Florence, Florence, Italy.
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Home PD, Mehta R, Hafidh KAS, Gurova OY, Alvarez A, Serafini P, Pourrahmat M. Efficacy and safety of iGlarLixi versus IDegAsp: Results of a systematic literature review and indirect treatment comparison. Diabetes Obes Metab 2021; 23:2660-2669. [PMID: 34402153 PMCID: PMC9290816 DOI: 10.1111/dom.14518] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/23/2021] [Accepted: 08/03/2021] [Indexed: 12/21/2022]
Abstract
AIM To assess the efficacy and safety of iGlarLixi, a fixed-ratio combination of basal insulin glargine 100 U/mL and lixisenatide (glucagon-like peptide-1 receptor agonist) versus IDegAsp, a co-formulation of basal insulin degludec 100 U/mL with rapid-acting insulin aspart. MATERIALS AND METHODS A systematic literature search of randomized controlled trials (RCTs) was performed. Outcomes from eligible RCTs were compared by an indirect treatment comparison using a Bayesian framework. Subanalyses of Japanese and international trials were performed. RESULTS Eight RCTs (duration 26-30 weeks) were included. Mean difference in HbA1c change with iGlarLixi exceeded that for IDegAsp: -0.64 (95% credible interval -1.01, -0.28) %-units (-7.0 [-11.0, -3.1] mmol/mol) for all trials, -0.39 (-0.55, -0.23) %-units (-4.3 [-6.0, -2.5] mmol/mol) for international, and -0.88 (-1.11, -0.64) %-units (-9.6 [-12.1, -7.0] mmol/mol) for Japanese trials. HbA1c target achievement (<7.0%-units [<53 mmol/mol]) was greater for iGlarLixi in all trials (odds ratio 2.50 [1.06, 5.56]) and Japanese trials (2.17 [1.27, 3.70]), but not in international trials (2.17 [0.42, 11.11]). Analyses suggesting differences in mean postmeal self-measured plasma glucose were significantly lower by 1.0-2.0 mmol/L (18-36 mg/dL) with iGlarLixi in all analyses. Bodyweight change was more favourable (1-2 kg) for iGlarLixi versus IDegAsp for all analyses (P < 0.05). Comparisons of hypoglycaemia were inconclusive owing to differences in definitions between studies. Adverse events were more frequent with iGlarLixi because of gastrointestinal intolerance. CONCLUSIONS iGlarLixi appears to offer clinical benefit in glucose control and bodyweight change in people needing both basal and meal-time intervention.
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Affiliation(s)
- Philip D. Home
- Translational and Clinical Research InstituteNewcastle UniversityNewcastle upon TyneUK
| | - Roopa Mehta
- Metabolic Diseases Research Unit (UIEM)National Institute of Medical Sciences and Nutrition Salvador Zubiran (INCMNSZ)Mexico CityMexico
| | - Khadija A. S. Hafidh
- Department of Internal Medicine, Diabetology UnitRashid Hospital, Dubai Health AuthorityDubaiUnited Arab Emirates
| | | | | | - Paul Serafini
- Evidinno Outcomes Research Inc.VancouverBritish ColumbiaCanada
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Abstract
At the time of its first clinical application 100 years ago, insulin was presented as the cure for people with diabetes mellitus. That transpired to be an overstatement, yet insulin has proven to be the lifesaver for people with type 1 diabetes mellitus and an essential therapy for many with type 2 diabetes mellitus or other forms of diabetes mellitus. Since its discovery, insulin (a molecule of only 51 amino acids) has been the subject of pharmaceutical research and development that has paved the way for other protein-based therapies. From purified animal-extracted insulin and human insulin produced by genetically modified organisms to a spectrum of insulin analogues, pharmaceutical laboratories have strived to tailor the preparations to the needs of patients. Nonetheless, overall glycaemic control often remains poor as exogenous insulin is still not able to mimic the physiological insulin profile. Circumventing subcutaneous administration and the design of analogues with profiles that mimic that of physiological insulin are ongoing areas of research. Novel concepts, such as once-weekly insulins or glucose-dependent and oral insulins, are on the horizon but their real-world effectiveness still needs to be proven. Until a true cure for type 1 diabetes mellitus is found and the therapeutic arsenal for other forms of diabetes mellitus is expanded, insulin will remain central in the treatment of many people living with diabetes mellitus.
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Affiliation(s)
- Chantal Mathieu
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
- Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
| | - Pieter-Jan Martens
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
- Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Roman Vangoitsenhoven
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
- Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
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21
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Moon S, Chung HS, Kim YJ, Yu JM, Jeong WJ, Park J, Oh CM. Efficacy and Safety of Insulin Degludec/Insulin Aspart Compared with a Conventional Premixed Insulin or Basal Insulin: A Meta-Analysis. Metabolites 2021; 11:metabo11090639. [PMID: 34564455 PMCID: PMC8470485 DOI: 10.3390/metabo11090639] [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: 08/07/2021] [Revised: 09/12/2021] [Accepted: 09/15/2021] [Indexed: 11/29/2022] Open
Abstract
Insulin degludec/insulin aspart (IDegAsp) is a novel co-formulation of 70% insulin degludec and 30% insulin aspart. The present meta-analysis was conducted to assess the efficacy and safety of IDegAsp compared with a conventional premixed insulin or basal insulin. We extracted data from citation databases, including PubMed, EMBASE, and the Cochrane Library, since inception to 2021. We calculated the mean differences for hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), self-measured mean glucose, and postprandial glucose (PPG) and odds ratios for confirmed hypoglycemia events. Compared with twice-daily conventional premixed insulin, twice-daily IDegAsp showed a similar effect on changes in HbA1c, but it significantly reduced FPG and self-measured mean glucose levels. Furthermore, compared to once-daily basal insulin, once-daily IDegAsp had a similar effect on changes in HbA1c, but it significantly reduced self-measured mean glucose and PPG levels. The risk of overall confirmed hypoglycemia was similar between treatments; however, the risk of nocturnal hypoglycemia events was significantly lower with IDegAsp than with conventional premixed insulin and basal insulin. Thus, IDegAsp was more effective than conventional premixed insulin and basal insulin at reducing blood glucose with fewer nocturnal hypoglycemia events.
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Affiliation(s)
- Shinje Moon
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon 24252, Korea
| | - Hye-Soo Chung
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon 24252, Korea
| | - Yoon-Jung Kim
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon 24252, Korea
| | - Jae-Myung Yu
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon 24252, Korea
| | - Woo-Ju Jeong
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Korea
| | - Jiwon Park
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Korea
| | - Chang-Myung Oh
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Korea
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22
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Shigiyama F, Liu L, Nordahl H, Suzuki R, Yamamoto Y, Hirose T. A Real-World, Prospective, Non-interventional Study of Adults with T2D Switching to IDegAsp from Glargine U100 or U300 in Japan. Diabetes Ther 2021; 12:2405-2421. [PMID: 34304385 PMCID: PMC8385001 DOI: 10.1007/s13300-021-01117-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 07/07/2021] [Indexed: 12/25/2022] Open
Abstract
INTRODUCTION This real-world study investigated glycaemic control and quality of life (QoL) in insulin-experienced Japanese patients with type 2 diabetes (T2D) who switched to insulin degludec/insulin aspart (IDegAsp). METHODS This was a prospective, non-interventional, open-label, single-arm study. Eligible patients were adults (aged ≥ 20 years) with T2D, previously treated with insulin glargine 100 or 300 units/mL (glargine U100/U300) with or without prandial insulin, who switched to IDegAsp as part of routine practice. Change from baseline to end of study (EOS; 26 weeks after initiation or IDegAsp discontinuation) in the following endpoints was assessed by adjusted mixed models for repeated measures: glycated haemoglobin (HbA1c; primary endpoint), fasting plasma glucose (FPG), insulin dose and total Diabetes Therapy-Related Quality of Life (DTR-QoL) score. Non-severe hypoglycaemia was assessed in the 4-week period prior to initiating IDegAsp and in the 4-week period before EOS or discontinuation using negative binomial regression. RESULTS The full analysis set included 236 patients from 29 centres in Japan with mean (± SD) age 63.2 years (± 12.3), HbA1c 7.7% (± 1.0) and diabetes duration 14.9 (± 9.3) years. After 26 weeks with IDegAsp, HbA1c (estimated change - 0.1% [- 0.2; 0.0]95% confidence interval (CI), p = 0.3036) and FPG (- 7.5 mg/dL [- 23.5; 8.5]95% CI, p = 0.3477) were maintained; there were significant reductions in basal and total insulin dose: estimated change of - 3.4 units/day [- 3.8; - 3.0]95% CI and - 1.0 units/day [- 1.9; - 0.1]95% CI, respectively (both p < 0.05). Non-severe hypoglycaemia rates were similar in the periods before and after initiating IDegAsp, while there was a significant improvement in total DTR-QoL score after 26 weeks with IDegAsp (p = 0.0012). CONCLUSION These real-world data suggest that switching to IDegAsp from glargine U100 or U300 was well tolerated in a Japanese population with T2D, with no new safety or tolerability signals, and associated with maintenance of glycaemic control and improved QoL. TRIAL REGISTRATION This study is registered at ClinicalTrials.gov: NCT03745157.
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Affiliation(s)
- Fumika Shigiyama
- Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan
| | - Lei Liu
- Novo Nordisk A/S, Søborg, Denmark
| | | | | | | | - Takahisa Hirose
- Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan.
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23
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Onder CE, Kuşkonmaz SM, Koc G, Firat S, Omma T, Taskaldiran I, Gokbulut P, Culha C. Factors that affect the Glycemic Control Achieved by Switching to Insulin Degludec/ Aspart in Insulin-Treated Patients with Type 1 and Type 2 Diabetes in a Real-World Setting: a Non-interventional, Retrospective Cohort Study. ACTA ENDOCRINOLOGICA-BUCHAREST 2021; 16:443-448. [PMID: 34084235 DOI: 10.4183/aeb.2020.443] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Background Insulin degludec/aspart (IDegAsp) is a co-formulation with IDeg and IAsp. Different insulin regimens may be switched to IDegAsp. In this study, we aimed to find out the effect of switch to IDegAsp on glycemic control and whether the basal characteristics and treatment modalities of the patients affect the change in glycemic control brought by switch to IDegAsp. Methods We retrospectively analyzed the records of 78 patients whose insulin therapies (basal+bolus, premixed analogues or basal only) were switched on a 1:1 unit basis to IDegAsp±bolus insulin. Oral antidiabetic agents (OADs) given were recorded. At the end of 12th and 24th week, total insulin doses of patients and HbA1c were compared to the baseline. Results There was a statistically significant decrease at HbA1c at 12 weeks (1.4%; p<0.001). There was not a significant difference in HbA1c between the OAD added group and the group with no new OADs(p=0.1). Basal insulin dose was not statistically different from baseline, whereas bolus insulin dose was significantly lower (p=0.007). At the end of 24 weeks the decrease in HbA1c level from baseline was preserved. Conclusion Regardless of the baseline insulin regimen, diabetes type and oral antidiabetic drugs given, HbA1c is significantly lowered after switching to IDegAsp.
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Affiliation(s)
- C E Onder
- Ankara Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - S M Kuşkonmaz
- Ankara Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - G Koc
- Ankara Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - S Firat
- Ankara Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - T Omma
- Ankara Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - I Taskaldiran
- Ankara Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - P Gokbulut
- Ankara Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
| | - C Culha
- Ankara Training and Research Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey
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24
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Aso Y, Takada Y, Tomotsune K, Chiba Y, Matsumura M, Jojima T, Sato M, Fujita N, Kuroda H, Murano S, Usui I. Comparison of insulin degludec (IDeg)/insulin Aspart (IAsp) co-formulation therapy twice-daily with free combination of GLP-1 receptor agonist liraglutide plus insulin degludec in Tochigi: IDEAL Trial. Int J Clin Pract 2021; 75:e13734. [PMID: 33099848 DOI: 10.1111/ijcp.13734] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 09/18/2020] [Indexed: 01/03/2023] Open
Abstract
AIM We compared the efficacy and safety of insulin degludec/insulin aspart co-formulation (IDegAsp) twice-daily to a free combination of basal insulin degludec and GLP-1 receptor agonist liraglutide (IDeg + Lira) once-daily for patients with inadequately controlled type 2 diabetes on insulin therapy and oral antidiabetic drugs. SUBJECTS AND METHODS Eligible patients were randomly allocated at a 1:1 ratio to receive either the once-daily dual injection of IDeg + Lira (n = 24) or twice-daily single injection of IDegAsp (n = 28). The primary endpoints were as follows: HbA1c changes over 52 weeks of treatment and the percentage of participants achieving HbA1c < 7.0% at week 52. RESULTS After 52 weeks, HbA1c decreased by 0.3% in the IDegAsp group and by 0.7% in the IDeg + Lira group. The HbA1c reduction was greater in the IDeg + Lira group than in the IDegAsp group. 19% of patients on IDegAsp versus 40% on IDeg + Lira achieved HbA1c < 7.0%. Pre-breakfast and pre-dinner blood glucose at 52 weeks were significantly lower in the IDeg + Lira group than in the IDegAsp group. The reduction in body mass index (BMI) was greater in the IDeg + Lira group than in the IDegAsp group throughout the study period. The confirmed hypoglycaemia rates were 1.32 and 0.69 per patient/year of exposure to IDegAsp and IDeg + Lira, respectively. CONCLUSIONS In patients with inadequately controlled type 2 diabetes on insulin therapy and oral antidiabetic drugs, treatment with the once-daily dual injection of IDeg + Lira compared with the twice-daily single injection of IDegAsp showed no significant difference in glycaemic control but statistically superior weight loss.
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Affiliation(s)
- Yoshimasa Aso
- Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan
| | | | - Ken Tomotsune
- Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi, Japan
| | | | | | - Teruo Jojima
- Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan
| | - Minoru Sato
- NHO Utsunomiya National Hospital, Utsunomiya, Tochigi, Japan
| | | | | | | | - Isao Usui
- Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan
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A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type 2 Diabetes in Clinical Practice: The JAGUAR Study. Adv Ther 2021; 38:1638-1649. [PMID: 33560496 PMCID: PMC7932946 DOI: 10.1007/s12325-021-01623-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 01/12/2021] [Indexed: 12/18/2022]
Abstract
Introduction The aim of this study was to evaluate the glycemic control and safety of insulin degludec/insulin aspart (IDegAsp) co-formulation in Japanese patients with type 2 diabetes (T2D) in a real-world clinical setting, including elderly patients (aged > 75 years). Methods Patients (≥ 18 years) diagnosed with T2D, previously treated with insulin were included from the Japanese Medical Data Vision database. Baseline data were taken at the index date, defined as the first IDegAsp prescription claim. Change in glycated hemoglobin (HbA1c) at 12 months was estimated using a mixed model repeated measures analysis. The proportion of patients achieving target HbA1c < 8.0% without experiencing hypoglycemia (identified by International Classification of Disease codes) was calculated at 12 months (365 ± 90 days) after baseline. Results Overall, 10,798 patients were included, 3940 were aged > 75 years, and 913 had baseline HbA1c values available. Switching to IDegAsp was associated with significantly improved HbA1c values at 12 months (− 1.23% [− 1.43, − 1.02]95%CI, p < 0.001) versus baseline. Moreover, relative to baseline, a significantly greater proportion of patients achieved HbA1c < 8.0% without hypoglycemia at 12 months, relative rate (RR) 1.30 [1.15, 1.45]95%CI, p < 0.001. Results were similar for patients aged ≤ 75 years and aged > 75 years; 66% and 64% of patients, respectively, achieved HbA1c < 8.0% without hypoglycemia at 12 months. Conclusion Switching from insulin to IDegAsp co-formulation was associated with significantly improved glycemic control and a reduction in hypoglycemia rate during 12 months of follow-up in Japanese patients with T2D, including those aged > 75 years. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01623-y.
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Demir T, Turan S, Unluhizarci K, Topaloglu O, Tukek T, Gogas Yavuz D. Use of Insulin Degludec/Insulin Aspart in the Management of Diabetes Mellitus: Expert Panel Recommendations on Appropriate Practice Patterns. Front Endocrinol (Lausanne) 2021; 12:616514. [PMID: 33776914 PMCID: PMC7996092 DOI: 10.3389/fendo.2021.616514] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Accepted: 01/18/2021] [Indexed: 12/20/2022] Open
Abstract
Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec (IDeg), which provides long-lasting basal insulin coverage, and insulin aspart (IAsp), which targets post-prandial glucose. This expert panel aimed to provide a practical and implementable guidance document to assist clinicians in prescribing IDegAsp in the diabetes management with respect to different patient populations including children and adults with type 1 diabetes (T1D) or type 2 diabetes (T2D) as well as pregnant, elderly and hospitalized patients and varying practice patterns (insulin-naive, insulin-treated, switching from basal, basal bolus and premix regimens). The experts recommended that IDegAsp can be used in insulin-naive T2D patients with poor glycemic control (HbA1c >8.5%) despite optimal oral antidiabetic drugs (OADs) as well as in insulin-treated T2D patients by switching from basal insulin, basal-bolus therapy or premixed insulins in relation to lower risk of nocturnal hypoglycemia, fewer injections and lower intraday glycemic variability, respectively. The experts considered the use of IDegAsp in children with T2D as a basal bolus alternative rather than as an alternative to basal insulin after metformin failure, use of IDegAsp in adult T1D patients as a simplified basal bolus regimen with lesser nocturnal hypoglycemia, fewer injections and better fasting plasma glucose control and in children with T1D as an alternative insulin regimen with fewer injection to increase treatment adherence. The proposed expert opinion provides practical information on use of IDegAsp in different patient populations and practice patterns to assist clinicians, which seems to compensate the need for easily implementable guidance on this novel insulin regimen.
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Affiliation(s)
- Tevfik Demir
- Department of Endocrinology and Metabolism, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey
| | - Serap Turan
- Department Pediatric Endocrinology, Marmara University Faculty of Medicine, Istanbul, Turkey
| | - Kursad Unluhizarci
- Department of Endocrinology and Metabolism, Erciyes University Faculty of Medicine, Kayseri, Turkey
| | - Oya Topaloglu
- Department of Endocrinology and Metabolism, Ankara Yildirim Beyazit University Faculty of Medicine, Ankara City Hospital, Ankara, Turkey
| | - Tufan Tukek
- Department of Endocrinology and Metabolism, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Dilek Gogas Yavuz
- Department of Endocrinology and Metabolism, Marmara University Faculty of Medicine, Istanbul, Turkey
- *Correspondence: Dilek Gogas Yavuz,
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Mehta R, Chen R, Hirose T, John M, Kok A, Lehmann R, Unnikrishnan AG, Yavuz DG, Fulcher G. Practical use of insulin degludec/insulin aspart in a multinational setting: beyond the guidelines. Diabetes Obes Metab 2020; 22:1961-1975. [PMID: 32618405 PMCID: PMC7689716 DOI: 10.1111/dom.14128] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 06/17/2020] [Accepted: 06/26/2020] [Indexed: 12/17/2022]
Abstract
Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec, which provides long-lasting basal insulin coverage, and insulin aspart, which targets postprandial glycaemia. This review provides expert opinion on the practical clinical use of IDegAsp, including: dose timings relative to meals, when and how to intensify treatment from once-daily (OD) to twice-daily (BID) dose adjustments, and use in special populations (including hospitalized patients). IDegAsp could be considered as one among the choices for initiating insulin treatment, preferential to starting on basal insulin alone, particularly for people with severe hyperglycaemia and/or when postprandial hyperglycaemia is a major concern. The recommended starting dose of IDegAsp is 10 units with the most carbohydrate-rich meal(s), followed by individualized dose adjustments. Insulin doses should be titrated once weekly in two-unit steps, guided by individualized fasting plasma glucose targets and based on patient goals, preferences and hypoglycaemia risk. Options for intensification from IDegAsp OD are discussed, which should be guided by HbA1c, prandial glucose levels, meal patterns and patient preferences. Recommendations for switching to IDegAsp from basal insulin, premixed insulins OD/BID, and basal-plus/basal-bolus regimens are discussed. IDegAsp can be co-administered with other antihyperglycaemic drugs; however, sulphonylureas frequently need to be discontinued or the dose reduced, and the IDegAsp dose may need to be decreased when sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists are added. Considerations around the initiation or continuation of IDegAsp in hospitalized individuals are discussed, as well as in those undergoing medical procedures.
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Affiliation(s)
- Roopa Mehta
- Unidad de Investigación en Enfermedades Metabólicas, Departamento de Endocrinología y MetabolismoInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico CityMexico
| | - Roger Chen
- Department of EndocrinologySt Vincentʼs HospitalSydneyAustralia
- University of New South Wales, Office of Medical EducationUniversity of SydneySydneyAustralia
| | - Takahisa Hirose
- Division of Diabetes, Metabolism and Endocrinology, Department of MedicineToho University School of MedicineTokyoJapan
| | - Mathew John
- Providence Endocrine and Diabetes Specialty CentreThiruvananthapuramKeralaIndia
| | - Adri Kok
- Netcare Union and Clinton HospitalsAlbertonSouth Africa
- University of WitwatersrandJohannesburgSouth Africa
| | - Roger Lehmann
- Department of EndocrinologyUniversity Hospital ZurichZurichSwitzerland
| | | | - Dilek Gogas Yavuz
- Department of Endocrinology and MetabolismMarmara University School of MedicineIstanbulTurkey
| | - Gregory Fulcher
- Northern Clinical SchoolUniversity of SydneySydneyAustralia
- Department of Diabetes, Endocrinology & MetabolismRoyal North Shore Hospital, University of SydneySydneyAustralia
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Cho KY, Nakamura A, Oba-Yamamoto C, Tsuchida K, Yanagiya S, Manda N, Kurihara Y, Aoki S, Atsumi T, Miyoshi H. Switching to Once-Daily Insulin Degludec/Insulin Aspart from Basal Insulin Improves Postprandial Glycemia in Patients with Type 2 Diabetes Mellitus: Randomized Controlled Trial. Diabetes Metab J 2020; 44:532-541. [PMID: 31769240 PMCID: PMC7453982 DOI: 10.4093/dmj.2019.0093] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 07/18/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND To explore the efficacy and safety of switching from once-daily basal insulin therapy to once-daily pre-meal injection insulin degludec/insulin aspart (IDegAsp) with respect to the glycemic control of participants with type 2 diabetes mellitus (T2DM). METHODS In this multicenter, open-label, prospective, randomized, parallel-group comparison trial, participants on basal insulin therapy were switched to IDegAsp (IDegAsp group; n=30) or continued basal insulin (Basal group; n=29). The primary endpoint was the superiority of IDegAsp in causing changes in the daily blood glucose profile, especially post-prandial blood glucose concentration after 12 weeks. RESULTS Blood glucose concentrations after dinner and before bedtime were lower in the IDegAsp group, and the improvement in blood glucose before bedtime was significantly greater in the IDegAsp group than in the Basal group at 12 weeks (-1.7±3.0 mmol/L vs. 0.3±2.1 mmol/L, P<0.05). Intriguingly, glycemic control after breakfast was not improved by IDegAsp injection before breakfast, in contrast to the favorable effect of injection before dinner on blood glucose after dinner. Glycosylated hemoglobin significantly decreased only in the IDegAsp group (58 to 55 mmol/mol, P<0.05). Changes in daily insulin dose, body mass, and recorded adverse effects, including hypoglycemia, were comparable between groups. CONCLUSION IDegAsp was more effective than basal insulin at reducing blood glucose after dinner and before bedtime, but did not increase the incidence of hypoglycemia. Switching from basal insulin to IDegAsp does not increase the burden on the patient and positively impacts glycemic control in patients with T2DM.
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Affiliation(s)
- Kyu Yong Cho
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan
| | - Akinobu Nakamura
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Chiho Oba-Yamamoto
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Kazuhisa Tsuchida
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Shingo Yanagiya
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | | | | | | | - Tatsuya Atsumi
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Hideaki Miyoshi
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
- Division of Diabetes and Obesity, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
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Glastras SJ, Cohen N, Dover T, Kilov G, MacIsaac RJ, McGill M, Fulcher GR. The Clinical Role of Insulin Degludec/Insulin Aspart in Type 2 Diabetes: An Empirical Perspective from Experience in Australia. J Clin Med 2020; 9:jcm9041091. [PMID: 32290465 PMCID: PMC7230791 DOI: 10.3390/jcm9041091] [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] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 04/08/2020] [Indexed: 12/26/2022] Open
Abstract
Treatment intensification in people with type 2 diabetes following failure of basal insulin commonly involves the addition of a rapid-acting insulin analogue (basal plus one or more prandial doses; multiple daily injections) or by a switch to premixed insulin. Insulin degludec/insulin aspart (IDegAsp), comprising rapid-acting insulin aspart and ultra-long-acting insulin degludec in solution, enables both fasting and post-prandial glucose control, with some advantages over other treatment intensification options. These include straightforward dose titration, flexibility in dose timing, low injection burden, simplicity of switching and a lower risk of hypoglycaemia. In Australia, where insulin degludec on its own is not available, IDegAsp enables patients to still benefit from its ultra-long-acting properties. This review aims to provide guidance on where and how to use IDegAsp. Specifically, guidance is included on the initiation of IDegAsp in insulin-naïve patients, treatment intensification from basal insulin, switching from premixed or basal-bolus insulin to IDegAsp, up-titration from once- to twice-daily IDegAsp and the use of IDegAsp in special populations or situations.
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Affiliation(s)
- Sarah J. Glastras
- Department of Diabetes, Endocrinology and Metabolism, The Royal North Shore Hospital, University of Sydney, Reserve Road, St Leonards NSW 2065, Australia;
- Correspondence: ; Tel.: +61-2-9463-1680
| | - Neale Cohen
- Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne VIC 3004, Australia;
| | - Thomas Dover
- Ipswich Hospital, University of Queensland, Chelmsford Avenue, Ipswich QLD 4305, Australia;
- Mater Hospital Brisbane, Raymond Terrace, South Brisbane QLD 4101, Australia
| | - Gary Kilov
- Launceston Diabetes Clinic, 247 Wellington Street, Launceston TAS 7250, Australia;
- Department of General Practice and Primary Health Care, University of Melbourne, 230 Gratton Street, Parkville VIC 3010, Australia
| | - Richard J. MacIsaac
- Department of Endocrinology & Diabetes, St Vincent’s Hospital Melbourne, University of Melbourne, 41 Victoria Parade, Fitzroy VIC 3065, Australia;
| | - Margaret McGill
- Diabetes Centre, Royal Prince Alfred Hospital, Sydney NSW 2050, Australia;
| | - Greg R. Fulcher
- Department of Diabetes, Endocrinology and Metabolism, The Royal North Shore Hospital, University of Sydney, Reserve Road, St Leonards NSW 2065, Australia;
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30
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Özçelik S, Çelik M, Vural A, Aydın B, Özçelik M, Gozu H. Outcomes of transition from premixed and intensive insulin therapies to insulin aspart/degludec co-formulation in type 2 diabetes mellitus: a real-world experience. Arch Med Sci 2020; 17:1-8. [PMID: 33488849 PMCID: PMC7811302 DOI: 10.5114/aoms.2020.93264] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 11/28/2019] [Indexed: 12/17/2022] Open
Abstract
INTRODUCTION To evaluate the efficacy and safety of transition from premixed and intensive insulin to twice-daily insulin degludec/aspart (IDegAsp) co-formulation in patients with type 2 diabetes mellitus. MATERIAL AND METHODS In this 12-week study, patients receiving twice-daily premixed insulin therapy in group 1 (n = 55) were switched to twice-daily IDegAsp. In group 2 (n = 60), patients on intensive insulin therapy were switched to IDegAsp injected twice a day. Inter- and intragroup comparisons were made. RESULTS A total of 115 patients were included in the study. There was a significant improvement in glycaemic control, median daily total insulin dose, body mass, body mass index, and hypoglycaemic events in group 1 and group 2 with the switch to IDegAsp (p < 0.05). The decrease in median daily total insulin dose requirement in group 2 was higher than that of group 1 (p = 0.001). There was no difference between groups in terms of other parameters (p > 0.05). CONCLUSIONS The current analysis indicates that IDegAsp treatment improves outcomes, with the most notable differences observed in daily total insulin requirement, body mass, and hypoglycaemia.
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Affiliation(s)
- Serhat Özçelik
- Department of Endocrinology and Metabolism, Adıyaman Training and Research Hospital, Adıyaman, Turkey
| | - Mehmet Çelik
- Department of Internal Medicine, Division of Endocrinology and Metabolism, Antalya Kepez State Hospital, Kepez, Turkey
| | - Aşkı Vural
- Division of Internal Medicine, Adıyaman Training and Research Hospital, Adıyaman, Turkey
| | - Bünyamin Aydın
- Department of Endocrinology and Metabolism, Adıyaman Training and Research Hospital, Adıyaman, Turkey
| | - Melike Özçelik
- Department of Internal Diseases, Umraniye Training and Research Hospital, University of Health Sciences, İstanbul, Turkey
| | - Hulya Gozu
- Department of Endocrinology and Metabolism, Marmara University Training and Research Hospital, Turkey
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Kumar A, Sharma S, Gupta A, Dasgupta A, Asirvatham A, Talwalkar P, Das A, Mohan V. Indian reality of managing type 2 diabetes: an expert review of global and national guidelines for optimum insulin use. JOURNAL OF DIABETOLOGY 2020. [DOI: 10.4103/jod.jod_59_20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Kawaguchi Y, Sawa J, Hamai C, Nishimura Y, Kumeda Y. Comparison of the efficacy and safety of insulin degludec/aspart (twice-daily injections), insulin glargine 300 U/mL, and insulin glulisine (basal-bolus therapy). J Diabetes Investig 2019; 10:1527-1536. [PMID: 30868726 PMCID: PMC6825933 DOI: 10.1111/jdi.13038] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 02/11/2019] [Accepted: 03/03/2019] [Indexed: 12/12/2022] Open
Abstract
AIMS/INTRODUCTION We compared the efficacy and safety of insulin degludec/aspart (IDegAsp) twice-daily injections with insulin glargine 300 U/mL and insulin glulisine basal-bolus therapy (Gla300/Glu) using insulin glargine 300 U/mL (Gla300) and insulin glulisine (Glu). MATERIALS AND METHODS A total of 20 patients with type 2 diabetes mellitus were treated with IDegAsp twice-daily injections; achievement of target preprandial glucose concentration of 100-130 mg/dL at breakfast and supper was determined using a wearable flash glucose monitoring system. Patients were later switched to Gla300/Glu basal-bolus therapy before breakfast and before supper. Data were collected on days 2-4 and days 12-14 for each treatment period. The study's primary efficacy end-point was the mean percentage of time with a target glucose range of 70-180 mg/dL, and safety end-points were the mean percentage of time with hypoglycemia having glucose levels <70 mg/dL, clinically important hypoglycemia with glucose levels <54 mg/dL and nocturnal (00.00-06.00) hypoglycemia. RESULTS Considering efficacy, the mean percentage of time for the target glucose range of IDegAsp was significantly lower than that of Gla300/Glu (73.1 [69.4-81.1] vs 84.2 [80.2-93.1], P = 0.001). Considering safety, the mean percentages of hypoglycemia (<70 mg/dL; 2.1 [0.0-9.4] vs 14.4 [4.4-22.3]), clinically important hypoglycemia (<54 mg/dL; 0.0 [0.0-0.2] vs 1.9 [0.0-5.6]) and nocturnal (00.00-06.00 hours) hypoglycemia (0.5 [0.0-5.9] vs 8.9 [3.1-11.8]) of Gla300/Glu were significantly lower than those of IDegAsp (P = 0.012, 0.036 and 0.007, respectively). CONCLUSIONS When compared with the IDegAsp twice-daily injections, Gla300/Glu basal-bolus therapy might achieve more effective glycemic control without hypoglycemic risk.
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Affiliation(s)
- Yuji Kawaguchi
- Department of Internal MedicineMinamiosaka HospitalOsakaJapan
| | - Jun Sawa
- Department of Internal MedicineMinamiosaka HospitalOsakaJapan
| | - Chie Hamai
- Department of Internal MedicineMinamiosaka HospitalOsakaJapan
| | - Yuri Nishimura
- Department of Internal MedicineMinamiosaka HospitalOsakaJapan
| | - Yasuro Kumeda
- Department of Internal MedicineMinamiosaka HospitalOsakaJapan
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Lechleitner M, Clodi M, Abrahamian H, Brath H, Brix J, Drexel H, Fasching P, Föger B, Francesconi C, Fröhlich-Reiterer E, Harreiter J, Hofer SE, Hoppichler F, Huber J, Kaser S, Kautzky-Willer A, Ludvik B, Luger A, Mader JK, Paulweber B, Pieber T, Prager R, Rami-Merhar B, Resl M, Riedl M, Roden M, Saely CH, Schelkshorn C, Schernthaner G, Sourij H, Stechemesser L, Stingl H, Toplak H, Wascher TC, Weitgasser R, Winhofer-Stöckl Y, Zlamal-Fortunat S. [Insulin therapy of type 2 diabetes mellitus (Update 2019)]. Wien Klin Wochenschr 2019; 131:39-46. [PMID: 30980147 DOI: 10.1007/s00508-019-1492-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The present article is a recommendation of the Austrian Diabetes Association for the practical use of insulin in type 2 diabetes, including the various insulin regimens.
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Affiliation(s)
- Monika Lechleitner
- Interne Abteilung, Landeskrankenhaus Hochzirl - Natters, Hochzirl, 6170, Zirl, Österreich.
| | - Martin Clodi
- ICMR - Institute for Cardiovascular and Metabolic Research, Johannes Kepler Universität Linz, Linz, Österreich.,Abteilung für Innere Medizin, Konventhospital der Barmherzigen Brüder Linz, Linz, Österreich
| | | | - Helmut Brath
- Diabetes Ambulanz, Gesundheitszentrum Wien-Süd, Wien, Österreich
| | - Johanna Brix
- 1. Medizinische Abteilung mit Diabetologie, Endokrinologie und Nephrologie, Krankenanstalt Rudolfstiftung, Wien, Österreich
| | - Heinz Drexel
- Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Österreich.,Private Universität im Fürstentum Liechtenstein, Triesen, Liechtenstein.,Drexel University College of Medicine, Philadelphia, PA, USA.,Abteilung für Angiologie, Universitätsspital Bern, Bern, Schweiz.,Chair der ESC-Working Group "Cardiovascular Pharmacotherapy", Sophia Antipolis, Frankreich
| | - Peter Fasching
- 5. Medizinische Abteilung für Endokrinologie, Rheumatologie und Akutgeriatrie, Wilhelminenspital der Stadt Wien, Wien, Österreich
| | - Bernhard Föger
- Interne Abteilung, Landeskrankenhaus Bregenz, Bregenz, Österreich.,AKS Gesundheit, Bregenz, Österreich
| | | | - Elke Fröhlich-Reiterer
- Universitätsklinik für Kinder- und Jugendheilkunde, Medizinische Universität Graz, Graz, Österreich
| | - Jürgen Harreiter
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Sabine E Hofer
- Department für Pädiatrie 1, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Friedrich Hoppichler
- Abteilung für Innere Medizin, Krankenhaus der Barmherzigen Brüder Salzburg, Salzburg, Österreich
| | - Joakim Huber
- Interne Abteilung mit Akutgeriatrie und Palliativmedizin, Franziskus Spital, Standort Landstraße, Wien, Österreich
| | - Susanne Kaser
- Department für Innere Medizin I, Medizinische Universität Innsbruck, Innsbruck, Österreich.,Christian Doppler Labor für Insulinresistenz, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Alexandra Kautzky-Willer
- Gender Medicine Unit, Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Bernhard Ludvik
- 1. Medizinische Abteilung mit Diabetologie, Endokrinologie und Nephrologie, Krankenanstalt Rudolfstiftung, Wien, Österreich
| | - Anton Luger
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Julia K Mader
- Klinische Abteilung für Endokrinologie und Diabetologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Österreich
| | - Bernhard Paulweber
- Universitätsklinik für Innere Medizin I, mit Gastroenterologie, Hepatologie, Nephrologie, Stoffwechsel und Diabetologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich
| | - Thomas Pieber
- Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Österreich
| | - Rudolf Prager
- 3. Medizinische Abteilung mit Stoffwechselerkrankungen und Nephrologie, Krankenhaus Hietzing, Wien, Österreich
| | - Birgit Rami-Merhar
- Universitätsklinik für Kinder- und Jugendheilkunde, Medizinische Universität Wien, Wien, Österreich
| | - Michael Resl
- Abteilung für Innere Medizin, Konventhospital der Barmherzigen Brüder Linz, Linz, Österreich
| | - Michaela Riedl
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Michael Roden
- Klinik für Endokrinologie und Diabetologie, Medizinische Fakultät, Heinrich-Heine-Universität, Düsseldorf, Deutschland.,Institut für Klinische Diabetologie, Deutsches Diabetes-Zentrum (DDZ), Leibniz-Zentrum für Diabetesforschung, Düsseldorf, Deutschland.,Deutsches Zentrum für Diabetesforschung, DZD e. V., München-Neuherberg, Deutschland
| | - Christoph H Saely
- Abteilung für Innere Medizin I, Akademisches Lehrkrankenhaus Feldkirch, Feldkirch, Österreich
| | | | - Guntram Schernthaner
- 1. Medizinische Abteilung mit Diabetologie, Endokrinologie und Department für Nephrologie, Krankenanstalt Rudolfstiftung, Wien, Österreich
| | - Harald Sourij
- Klinische Abteilung für Endokrinologie und Diabetologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Österreich
| | - Lars Stechemesser
- Universitätsklinik für Innere Medizin I, mit Gastroenterologie, Hepatologie, Nephrologie, Stoffwechsel und Diabetologie, Paracelsus Medizinische Privatuniversität, Salzburg, Österreich
| | - Harald Stingl
- Abteilung für Innere Medizin, Landesklinikum Melk, Melk, Österreich
| | - Hermann Toplak
- Klinische Abteilung für Endokrinologie und Diabetologie, Universitätsklinik für Innere Medizin, Medizinische Universität Graz, Graz, Österreich
| | - Thomas C Wascher
- 1. Medizinische Abteilung, Hanusch-Krankenhaus, Wien, Österreich
| | - Raimund Weitgasser
- Abteilung für Innere Medizin, Privatklinik Wehrle-Diakonissen, Salzburg, Österreich.,Universitätsklinik für Innere Medizin I, LKH Salzburg - Universitätsklinikum der Paracelsus Medizinischen Privatuniversität, Salzburg, Österreich
| | - Yvonne Winhofer-Stöckl
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Sandra Zlamal-Fortunat
- Abteilung für Innere Medizin und Gastroenterologie, Klinikum Klagenfurt am Wörthersee, Klagenfurt, Österreich
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Shimoda S, Sakamoto W, Hokamura A, Matsuo Y, Sekigami T, Ichimori S, Iwashita S, Ishii N, Otsu K, Yoshimura R, Nishiyama T, Sakaguchi M, Nishida K, Araki E. Comparison of the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) and long-acting second-generation basal insulin (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes: a pilot, randomized, controlled study. Endocr J 2019; 66:745-752. [PMID: 31308304 DOI: 10.1507/endocrj.ej19-0179] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
To examine the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) or once-daily second-generation basal insulin analogs (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes in routine clinical practice. A 12-week multicenter, open-label, randomized, pilot study was performed in 52 subjects with type 2 diabetes treated with oral antidiabetic drugs (OADs). Subjects were randomized to once-daily IDegAsp (n = 26) or basal insulin (n = 26). The primary endpoint was percent change in HbA1c from baseline to week 12. Furthermore, it was analyzed post hoc in subgroups stratified by baseline HbA1c. During a follow-up period, percent change in HbA1c was not significantly different between the two groups (p = 0.161). Daily insulin doses and frequency of overall hypoglycemia were also similar in the two groups. In post hoc analyses, once-daily basal insulin was more effective than IDegAsp in subjects with HbA1c more than or equal to 8.5% (p < 0.05); however, in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant improvement in percent change in HbA1c at week 12, compared with basal insulin (p < 0.01). Although there was no apparent difference in the HbA1c-lowering effects between two groups, when compared in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant effect in comparison with once-daily basal insulin. These findings suggest that the baseline HbA1c level might provide the important information for choosing IDegAsp or basal insulin in patients insufficiently controlled with OADs. This trial was registered with UMIN (no. UMIN000035431).
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Affiliation(s)
- Seiya Shimoda
- Division of Food & Health Environmental Sciences, Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto 862-8502, Japan
| | | | - Ayaka Hokamura
- Division of Food & Health Environmental Sciences, Faculty of Environmental and Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto 862-8502, Japan
| | - Yasuto Matsuo
- Department of Medical Oncology & Diabetes, Saiseikai Kumamoto Hospital, Kumamoto 861-4193, Japan
| | - Taiji Sekigami
- Sekigami Clinic, Division of Medicine & Diabetes and Endocrine, Kumamoto 866-0824, Japan
| | | | | | - Norio Ishii
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | - Kae Otsu
- Kumamoto Rousai Hospital, Kumamoto 866-8533, Japan
| | | | | | - Masaji Sakaguchi
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
| | | | - Eiichi Araki
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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Yang W, Ma J, Hong T, Liu M, Miao H, Peng Y, Wang C, Xu X, Yang T, Nielsen AM, Pan L, Liu W, Zhao W. Efficacy and safety of insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Chinese adults with type 2 diabetes: A phase III, open-label, 2:1 randomized, treat-to-target trial. Diabetes Obes Metab 2019; 21:1652-1660. [PMID: 30869183 PMCID: PMC6617768 DOI: 10.1111/dom.13703] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 03/01/2019] [Accepted: 03/11/2019] [Indexed: 11/30/2022]
Abstract
AIMS To assess the efficacy and safety of twice-daily insulin degludec/insulin aspart (IDegAsp) versus biphasic insulin aspart 30 (BIAsp 30) twice daily, both ± metformin, in Chinese adults (N = 543) with type 2 diabetes (T2D) inadequately controlled on premixed/self-mixed or basal insulin ± metformin. MATERIALS AND METHODS We conducted a 26-week, phase III, open-label, treat-to-target, 2:1 randomized trial. Hierarchical testing was used with non-inferiority of glycated haemoglobin (HbA1c) change from baseline to week 26 as the primary endpoint and superiority for the confirmatory secondary endpoints which were as follows: change from baseline in fasting plasma glucose (FPG); nocturnal confirmed hypoglycaemic episodes (12:01-5:59 am, inclusive); total confirmed hypoglycaemic episodes (severe or plasma glucose <3.1 mmol/L with/without symptoms); body weight; and percentage of responders (HbA1c <53 mmol/mol [<7.0%]) without confirmed hypoglycaemic episodes. RESULTS Non-inferiority for change from baseline to week 26 in HbA1c and superiority of IDegAsp twice daily versus BIAsp 30 twice daily for change in FPG, nocturnal confirmed and total confirmed hypoglycaemic episodes, was demonstrated. Estimated rates of nocturnal confirmed and total confirmed hypoglycaemic episodes were 47% and 43% lower, respectively, with IDegAsp twice daily versus BIAsp 30 twice daily. Superiority for change in body weight was not confirmed. Participants were more likely to reach the HbA1c goal of <53 mmol/mol (<7.0%) without confirmed hypoglycaemia with IDegAsp twice daily versus BIAsp 30 twice daily by trial end. No new safety signals were identified. CONCLUSIONS The efficacy and safety of IDegAsp in Chinese patients with T2D was demonstrated, confirming results from international trials.
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Affiliation(s)
| | | | | | - Ming Liu
- Tianjin Medical University General HospitalTianjinChina
| | - Heng Miao
- Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Yongde Peng
- Shanghai First People's HospitalShanghaiChina
| | - Changjiang Wang
- First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Xiangjin Xu
- Fuzhou General Hospital of Nanjing Military CommandFuzhouChina
| | - Tao Yang
- Jiangsu Province HospitalJiangsuChina
| | - Anne M. Nielsen
- Medical & Science Degludec Portfolio, Novo Nordisk A/SSøborgDenmark
| | - Lili Pan
- Novo Nordisk (China) Pharmaceuticals Co. LtdBeijingChina
| | - Weihong Liu
- Novo Nordisk (China) Pharmaceuticals Co. LtdBeijingChina
| | - Weigang Zhao
- Peking Union Medical College HospitalBeijingChina
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36
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Fulcher G, Mehta R, Fita EG, Ekelund M, Bain SC. Efficacy and Safety of IDegAsp Versus BIAsp 30, Both Twice Daily, in Elderly Patients with Type 2 Diabetes: Post Hoc Analysis of Two Phase 3 Randomized Controlled BOOST Trials. Diabetes Ther 2019; 10:107-118. [PMID: 30474818 PMCID: PMC6349271 DOI: 10.1007/s13300-018-0531-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Indexed: 01/01/2023] Open
Abstract
INTRODUCTION The majority of elderly patients (≥ 65 years of age) with type 2 diabetes mellitus (T2DM) will eventually require insulin therapy, but they are particularly vulnerable to hypoglycemia and challenging to treat. Insulin degludec/insulin aspart (IDegAsp) is a novel co-formulation of 70% insulin degludec and 30% insulin aspart administered in a single injection, either once or twice daily with main meals. METHODS A combined analysis of the phase 3 BOOST INTENSIFY PREMIX I (NCT01009580) and BOOST INTENSIFY ALL (NCT01059812) trials has previously reported lower rates of hypoglycemia during the maintenance period in patients with T2DM treated with IDegAsp twice daily (BID) versus biphasic insulin aspart 30 (BIAsp 30) BID. This post hoc analysis examined the safety and efficacy of IDegAsp versus BIAsp 30 in elderly patients from the global population of these two trials, and also from the Japanese cohort of BOOST INTENSIFY ALL. RESULTS Change in HbA1c was similar for IDegAsp versus BIAsp 30 (p > 0.5). Compared with BIAsp 30, IDegAsp resulted in significant reductions in fasting plasma glucose (p < 0.0001), numerically lower rates of overall and nocturnal hypoglycemia (global estimated rate ratios: 0.92 [0.67; 1.26]95% confidence interval [CI], p = 0.5980 and 0.67 [0.39; 1.18]95% CI, p = 0.1676, respectively), and a significantly lower total daily insulin dose at end of trial (global estimated treatment difference 0.79 [0.73; 0.87]95% CI, p < 0.0001) in elderly patients. CONCLUSION The results described here are consistent with those of the overall trial populations, demonstrating that IDegAsp BID is efficacious in elderly patients and suggesting that there is no need for special safety precautions. FUNDING Novo Nordisk. TRIAL REGISTRATION ClinicalTrials.gov identifiers, NCT01009580 and NCT01059812. Plain language summary available for this article.
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Affiliation(s)
- Greg Fulcher
- Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia.
| | - Roopa Mehta
- Unidad de Investigación en Enfermedades Metabólicas, Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | | | | | - Stephen C Bain
- Diabetes Research Unit Cymru, Swansea University, ABM University Health Board, Swansea, UK
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Kalra S, Atkin S, Cervera A, Das AK, Demir O, Demir T, Fariduddin M, Vo KT, Ku BJ, Kumar A, Latif ZA, Malek R, Matawaran BJ, Mehta R, Tran NQ, Panelo A, Ruder S, Saldana JR, Shaikh KA, Shakya A, Shrestha D, Unnikrishnan AG. Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp). Adv Ther 2018; 35:928-936. [PMID: 29796928 PMCID: PMC11343968 DOI: 10.1007/s12325-018-0712-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Indexed: 12/13/2022]
Abstract
Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.
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Affiliation(s)
- Sanjay Kalra
- Department of Endocrinology, Bharti Hospital Karnal, Karnal, India.
| | - Stephen Atkin
- Department of Medicine, Weill Cornell Medical College, Doha, Qatar
| | - Antonio Cervera
- Department of Endocrinology, Clínica de Mérida, Mérida, Yucatán, Mexico
| | | | - Ozgur Demir
- Department of Endocrinology and Metabolic Diseases, İbni Sina Hospital, Ankara, Turkey
| | - Tevfik Demir
- Department of Endocrinology and Metabolic Disease, Dokuz Eylul University, Balcova, İzmir, Turkey
| | - Md Fariduddin
- Department of Endocrinology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Khoa Tuan Vo
- Department of Endocrinology, 115 Hospital, Ho Chi Minh City, Vietnam
| | - Bon Jeong Ku
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea
| | - Ajay Kumar
- Department of Diabetology, Diabetes Care and Research Center, Patna, Bihar, India
| | - Zafar A Latif
- Department of Endocrinology, General, BIRDEM Hospital, BIRDEM Academy, Dhaka, Bangladesh
| | - Rachid Malek
- Department of Medicine, Ferhat Abbas University of Setif, Setif, Algeria
| | - Bien J Matawaran
- Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Santo Tomas, Manila, Philippines
| | - Roopa Mehta
- Department of Endocrinology and Nutritión, Instituto nacional de ciencias médicas y nutrición, Salvador Zubirán, Mexico City, Mexico
| | - Nam Quang Tran
- Head of Endocrinology Department, Ho Chi Minh City University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam
| | - Araceli Panelo
- Department of Medicine, UERMMMC College of Medicine, Manila, Philippines
| | - Sundeep Ruder
- Department of Endocrinology and Metabolism, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa
| | | | - Khalid A Shaikh
- Department of Diabetes, Faculty of Internal Medicine, Royal Oman Police Hospital, Muscat, Oman
| | - Amit Shakya
- Department of Endocrinology, Diabetes Thyroid Endocrine Center, Kathmandu, Nepal
| | - Dina Shrestha
- Department of Endocrinology, Norvic International Hospital, Kathmandu, Nepal
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Haluzík M, Fulcher G, Pieber TR, Bardtrum L, Tutkunkardas D, Rodbard HW. The co-formulation of insulin degludec and insulin aspart lowers fasting plasma glucose and rates of confirmed and nocturnal hypoglycaemia, independent of baseline glycated haemoglobin levels, disease duration or body mass index: A pooled meta-analysis of phase III studies in patients with type 2 diabetes. Diabetes Obes Metab 2018; 20:1585-1592. [PMID: 29451706 PMCID: PMC6033009 DOI: 10.1111/dom.13261] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 02/09/2018] [Accepted: 02/12/2018] [Indexed: 01/17/2023]
Abstract
AIMS To investigate whether the proven benefits of insulin degludec (IDeg) combined with insulin aspart (IAsp), known as IDegAsp, given twice daily, extend across a wide spectrum of patients with diabetes. MATERIALS AND METHODS This was a post hoc pooled analysis of 5 phase III randomized, 26-week, open-label, treat-to-target trials comparing IDegAsp twice daily (n = 1111) with one of two comparators: premixed insulin (biphasic insulin aspart 30 [BIAsp 30]) twice daily (n = 561) or IDeg once daily + IAsp (n = 136). Patient data were stratified according to baseline glycated haemoglobin (HbA1c) or fasting plasma glucose (FPG) categories, as well as by baseline duration of diabetes or body mass index (BMI) categories. RESULTS We conducted a meta-analysis of 5 clinical trials: NCT01513590, NCT01009580, NCT01059812, NCT01680341 and NCT01713530. End-of-trial results were broadly consistent, with differences between IDegAsp and comparators observed in phase III trials. HbA1c results were similar for IDegAsp and the comparators in all baseline characteristic (HbA1c, duration of diabetes or BMI) and category groups (number ranges). Significantly lower FPG level was observed with IDegAsp vs comparators in all baseline characteristic and most category groups (excluding FPG <5.5 mmol/L). Significantly lower insulin doses were observed with IDegAsp vs comparators in all baseline characteristic and half of the category groups, and significantly lower rates of confirmed and nocturnal confirmed hypoglycaemia were observed with IDegAsp vs comparators in all baseline variable and category groups. CONCLUSIONS IDegAsp retains a consistent safety and efficacy profile in patients with different baseline characteristics.
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Affiliation(s)
- Martin Haluzík
- Institute for Clinical and Experimental Medicine and Charles UniversityPragueCzech Republic
| | - Greg Fulcher
- Royal North Shore HospitalUniversity of SydneySydneyAustralia
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Johnson EL, Frias JP, Trujillo JM. Anticipatory guidance in type 2 diabetes to improve disease management; next steps after basal insulin. Postgrad Med 2018; 130:365-374. [PMID: 29569978 DOI: 10.1080/00325481.2018.1452515] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The alarming rise in the number of people living with type 2 diabetes (T2D) presents primary care physicians with increasing challenges associated with long-term chronic disease care. Studies have shown that the majority of patients are not achieving or maintaining glycemic goals, putting them at risk of a wide range of diabetes-related complications. Disease- and self-management programs have been shown to help patients improve their glycemic control, and are likely to be of particular benefit for patients with diabetes dealing with these issues. Anticipatory guidance is an individualized, proactive approach to patient education and counseling by a health-care professional to support patients in better coping with problems before they arise. It has been shown to improve disease outcomes in a variety of chronic conditions, including diabetes. While important at all stages, anticipatory guidance may be of particular importance during changes in treatment regimens, and especially during transition to, and escalation of, insulin-based regimens. The aim of this article is to provide advice to physicians on anticipatory guidance for basal-insulin dosing, focusing on appropriate basal-insulin-dose increase and prevention of potentially deleterious basal-insulin doses, so called overbasalization. It also provides an overview of new treatment options for patients with T2D who are not well controlled on basal-insulin therapy, fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists, and advice on the type of anticipatory guidance needed to ensure safe and appropriate switching to these therapies.
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Affiliation(s)
- Eric L Johnson
- a Department of Family and Community Medicine , University of North Dakota , Grand Forks , ND , USA
| | - Juan P Frias
- b National Research Institute , Los Angeles , CA , USA
| | - Jennifer M Trujillo
- c Skaggs School of Pharmacy and Pharmaceutical Sciences , University of Colorado , Aurora , CO , USA
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Liebl A, Mohan V, Yang W, Strojek K, Linjawi S. 15 Years of Experience with Biphasic Insulin Aspart 30 in Type 2 Diabetes. Drugs R D 2018; 18:27-39. [PMID: 29468559 PMCID: PMC5833912 DOI: 10.1007/s40268-018-0228-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Since clinical experience with biphasic insulin aspart 30 (BIAsp 30) in type 2 diabetes mellitus (T2DM) was reviewed in 2012 after 10 years of use worldwide, additional studies have been published that highlight new aspects, including use in real-world populations. Evidence from 35 new studies confirms and builds upon previous work indicating that BIAsp 30 continues to have pharmacodynamic and clinical advantages over biphasic human insulin (BHI 30), including in real-world practice with unselected populations of patients. BIAsp 30 has also been shown to be safe and efficacious as an add-on to dipeptidyl peptidase-4 (DPP-4) inhibitors. Intensification with BIAsp 30 is a safe and effective way to improve glycemic control, and titration performed by patients can achieve results that are at least comparable to those when being guided by healthcare providers. Stepwise intensification using BIAsp 30 is comparable to intensification using a basal-bolus regimen, and twice-daily BIAsp 30 provides similar glycemic control to a basal-plus regimen. Data from large observational studies, in particular, have identified patient-related characteristics that are associated with improved clinical responses, suggesting that earlier initiation and intensification of therapy is warranted. Finally, new health-economic analyses continue to confirm that BIAsp 30 is cost effective versus other therapies such as BHI 30, neutral protamine Hagedorn (NPH), or insulin glargine in both insulin-naïve and insulin-experienced patients. After 15 years of clinical use worldwide, analysis of more recent 5-year data indicates that BIAsp 30 remains a safe, effective, and simple-to-use insulin for initiation and intensification by diabetes specialists and primary care physicians in a variety of patients with T2DM.
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Affiliation(s)
- Andreas Liebl
- Department for Internal Medicine, Center for Diabetes and Metabolism, m&i-Fachklinik Bad Heilbrunn, Woernerweg 30, 83670, Bad Heilbrunn, Germany.
| | - Viswanathan Mohan
- Dr. Mohan's Diabetes Specialties Centre and Madras Diabetes Research Foundation, Chennai, India
| | | | - Krzysztof Strojek
- Department of Internal Diseases Diabetology and Cardiometabolic Diseases, SMDZ in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Sultan Linjawi
- Coffs Endocrine and Diabetes Services, Coffs Harbour, NSW, 2450, Australia
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Umpierrez GE, Bailey TS, Carcia D, Shaefer C, Shubrook JH, Skolnik N. Improving postprandial hyperglycemia in patients with type 2 diabetes already on basal insulin therapy: Review of current strategies. J Diabetes 2018; 10:94-111. [PMID: 28581207 DOI: 10.1111/1753-0407.12576] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 05/02/2017] [Accepted: 05/21/2017] [Indexed: 11/28/2022] Open
Abstract
A large number of patients with type 2 diabetes (T2D) on basal insulin do not reach their HbA1c goals and require additional therapy to address postprandial hyperglycemia. Guidelines from expert bodies have outlined several approaches to accomplish postprandial glucose (PPG) control, and recent literature suggests several more. This article provides strategies for primary care physicians caring for patients with T2D who do not achieve glycemic control with basal insulin alone. Current treatment guidelines and strategies for improving PPG control are reviewed, including the efficacy, safety, and cost-effectiveness of rapid-acting insulin (RAI) analogs, premixed insulin, glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, and α-glucosidase inhibitors. Other approaches, such as combinations of newer basal insulin plus RAI and a fixed-ratio combination of basal insulin and a GLP-1 RA, are also described.
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Affiliation(s)
| | | | - Danielle Carcia
- Abington Hospital Jefferson Health, Abington, Pennsylvania, USA
| | | | | | - Neil Skolnik
- Abington Hospital Jefferson Health, Abington, Pennsylvania, USA
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Hassanein M, Echtay AS, Malek R, Omar M, Shaikh SS, Ekelund M, Kaplan K, Kamaruddin NA. Original paper: Efficacy and safety analysis of insulin degludec/insulin aspart compared with biphasic insulin aspart 30: A phase 3, multicentre, international, open-label, randomised, treat-to-target trial in patients with type 2 diabetes fasting during Ramadan. Diabetes Res Clin Pract 2018; 135:218-226. [PMID: 29183844 DOI: 10.1016/j.diabres.2017.11.027] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Accepted: 11/08/2017] [Indexed: 01/24/2023]
Abstract
AIMS To compare the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) before, during and after Ramadan in patients with type 2 diabetes mellitus (T2DM) who fasted during Ramadan. METHODS In this multinational, randomised, treat-to-target trial, patients with T2DM who intended to fast and were on basal, pre- or self-mixed insulin ± oral antidiabetic drugs for ≥90 days were randomised (1:1) to IDegAsp twice daily (BID) or BIAsp 30 BID. Treatment period included pre-Ramadan treatment initiation (with insulin titration for 8-20 weeks), Ramadan (4 weeks) and post-Ramadan (4 weeks). Insulin doses were reduced by 30-50% for the pre-dawn meal (suhur) on the first day of Ramadan, and readjusted to the pre-Ramadan levels at the end of Ramadan. Hypoglycaemia was analysed as overall (severe or plasma glucose <3.1 mmol/L [56 mg/dL]), nocturnal (00:01-05:59) or severe (requiring assistance of another person). RESULTS During the treatment period, IDegAsp (n = 131) had significantly lower overall and nocturnal hypoglycaemia rates with similar glycaemic efficacy, versus BIAsp 30 (n = 132). During Ramadan, despite achieving significantly lower pre-iftar (meal at sunset) self-measured plasma glucose (estimated treatment difference: -0.54 mmol/L [-1.02; -0.07]95% CI, p = .0247; post hoc) with similar overall glycaemic efficacy, IDegAsp showed significantly lower overall and nocturnal hypoglycaemia rates versus BIAsp 30. CONCLUSIONS IDegAsp is a suitable therapeutic agent for patients who need insulin for sustained glucose control before, during and after Ramadan fasting, with a significantly lower risk of hypoglycaemia, versus BIAsp 30, an existing premixed insulin analogue.
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Affiliation(s)
- Mohamed Hassanein
- Endocrine Department, Dubai Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
| | - Akram Salim Echtay
- Internal Medicine Department, Head Division of Endocrinology, Rafic Hariri University Hospital, Bir Hassan, Jinah, POB: 5244, 2833-7401, Beirut, Lebanon.
| | - Rachid Malek
- Department of Internal Medicine, CHU Setif, 19000, Algeria.
| | - Mahomed Omar
- Department of Diabetes and Endocrinology, University of KwaZulu Natal, Durban, South Africa.
| | | | - Magnus Ekelund
- Novo Nordisk A/S, Vandtaarnsvej 114, DK 2860, Søborg, Denmark.
| | - Kadriye Kaplan
- Novo Nordisk A/S, Vandtaarnsvej 114, DK 2860, Søborg, Denmark.
| | - Nor Azmi Kamaruddin
- UKM Medical Centre, National University of Malaysia, Jalan Yaacob Latif, Bandar Tun Razal, Cheras Kuala Lumpur, Malaysia.
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Fujimoto K, Iwakura T, Aburaya M, Matsuoka N. Twice-daily insulin degludec/insulin aspart effectively improved morning and evening glucose levels and quality of life in patients previously treated with premixed insulin: an observational study. Diabetol Metab Syndr 2018; 10:64. [PMID: 30127860 PMCID: PMC6097398 DOI: 10.1186/s13098-018-0366-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 08/12/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Previous studies comparing insulin degludec/insulin aspart (IDegAsp) with premixed insulin twice daily among insulin users with type 2 diabetes have not thoroughly investigated differences in the glucose variability and psychological evaluations related to insulin regimen changes. We investigated changes in the daily and day-to-day glucose variability and quality of life (QOL) related to insulin use in patients with type 2 diabetes during a switch from premixed insulin preparations comprising either human insulin (BHI30) or insulin aspart (BIAsp30) to IDegAsp twice daily. METHODS In this prospective observational study, 22 subjects (BHI30:BIAsp30 = 12:10) self-measured their blood glucose levels every morning, and before and after all meals each week. Premixed insulin was administered for the first 2 months, followed by IDegAsp for the next 2 months. Efficacy measures were evaluated during the last month or last day of both phases. RESULTS The mean blood glucose levels (175.5 vs. 163.0 mg/dL; P = 0.004) and the M-values (53.9 vs. 27.6; P = 0.049) were significantly lower in the IDegAsp phase. However, no differences in the standard deviations of morning fasting glucose levels were observed between phases (premixed vs. IDegAsp, 20.0 vs. 19.3 mg/dL; P = 0.343). Compared to the premixed phase, the before-breakfast (145.3 vs. 126.0 mg/dL; P < 0.001), after-breakfast (190.3 vs. 170.7 mg/dL; P = 0.001), before-dinner (153.0 vs. 140.1 mg/dL; P = 0.007), and after-dinner glucose levels (198.7 vs. 181.4 mg/dL; P = 0.018) were lower in the IDegAsp phase. However, the before-lunch (150.8 vs. 148.2 mg/dL; P = 0.329) and after-lunch glucose levels (214.7 vs. 211.4 mg/dL; P = 0.308) did not significantly differ between phases. Regarding QOL, the total and therapy-related feeling Insulin Therapy Related-QOL (ITR-QOL) questionnaire scores favored IDegAsp, as did the ITR-QOL at Night questionnaire subscale score of glycemic control before breakfast. CONCLUSIONS Although the day-to-day variability of morning fasting glucose levels did not change, switching to IDegAsp improved daily glucose level variability, the morning and evening glucose control and QOL among patients treated with premixed insulin.Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000021939. Prospectively registered 18 April 2016.
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Affiliation(s)
- Kanta Fujimoto
- Department of Diabetes and Endocrinology, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-minamimachi, Chuo-ku, Kobe, 6500047 Japan
| | - Toshio Iwakura
- Department of Diabetes and Endocrinology, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-minamimachi, Chuo-ku, Kobe, 6500047 Japan
| | - Megumi Aburaya
- Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Naoki Matsuoka
- Department of Diabetes and Endocrinology, Kobe City Medical Center General Hospital, 2-1-1 Minatojima-minamimachi, Chuo-ku, Kobe, 6500047 Japan
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Haahr H, Fita EG, Heise T. A Review of Insulin Degludec/Insulin Aspart: Pharmacokinetic and Pharmacodynamic Properties and Their Implications in Clinical Use. Clin Pharmacokinet 2017; 56:339-354. [PMID: 27696221 PMCID: PMC5340839 DOI: 10.1007/s40262-016-0455-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Insulin degludec/insulin aspart (IDegAsp; 70 % IDeg and 30 % IAsp) is a soluble combination of two individual insulin analogues in one product, designed to provide mealtime glycaemic control due to the IAsp component and basal glucose-lowering effect from the IDeg component. The pharmacokinetic and pharmacodynamic characteristics of IDegAsp have been investigated in a series of clinical pharmacology studies with generally comparable designs, methodologies and patient inclusion/exclusion criteria. The glucose-lowering effect profile of IDegAsp during once-daily dosing at steady state shows distinct and clearly separated action from the prandial and basal components of IDegAsp. The IAsp component provides rapid onset and peak glucose-lowering effect followed by a flat glucose-lowering effect lasting beyond 30 h due to IDeg. During twice-daily dosing, the distinct peak effect and the flat basal effect are retained following each dose. The pharmacological properties of IDegAsp are maintained in the elderly, children, adolescents, Japanese patients and those with hepatic or renal impairment. The potential clinical benefits associated with the pharmacological properties of IDegAsp have been verified in phase III clinical trials comparing IDegAsp with three other currently available treatment options: premixed insulin, basal-bolus regimens and basal-only therapy. IDegAsp shows favourable clinical benefits compared with biphasic insulin aspart 30 and is a viable alternative to basal-bolus and basal-only therapy. This review presents the results from clinical pharmacology studies conducted with IDegAsp to date, and extrapolates these results to clinical use of IDegAsp in the context of findings from the IDegAsp clinical therapeutic studies.
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Affiliation(s)
- Hanne Haahr
- Clinical Pharmacology, Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.
| | - Edmond G Fita
- Global Medical Affairs, Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark
| | - Tim Heise
- Profil Institut für Stoffwechselforschung GmbH, Hellersbergstrasse 9, 41460, Neuss, Germany
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Ghosh S, Unnikrishnan AG, Saboo B, Kesavadev J, Aravind SR, Bajaj S, Rajput R, Seshadri K, Verma N, Gupta A, Makkar BM, Saikia M, Kale S, Damodaran S, Dengra A, Eashwar TKM, Maheshwari A, Pendsey S, Phatak SR, Sharma SK, Singh SK, Ramachandran A, Zargar AH, Joshi SR, Sadikot SM. Evidence-based recommendations for insulin intensification strategies after basal insulin in type 2 diabetes. Diabetes Metab Syndr 2017; 11 Suppl 1:S507-S521. [PMID: 28433618 DOI: 10.1016/j.dsx.2017.03.045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Indexed: 01/27/2023]
Abstract
Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients' exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy.
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Affiliation(s)
- Sujoy Ghosh
- Department of Endocrinology and Metabolism, Institute of Post-Graduate Medical Education and Research, Kolkata, India.
| | | | | | | | | | - Sarita Bajaj
- Department of Medicine, Motilal Nehru Medical College, Allahabad, India
| | - Rajesh Rajput
- Department of Endocrinology, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, India
| | - Krishna Seshadri
- Department of Endocrinology and Metabolism, Shri Rama Chandra University, Chennai, India
| | | | | | | | | | | | | | - Ashish Dengra
- Mahi Diabetes & Thyroid Care and Research Center, Jabalpur, India
| | | | - Anuj Maheshwari
- Department of Medicine, Babu Banarasi Das University, Lucknow, India
| | | | | | | | - Surya Kumar Singh
- Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | | | - Abdul H Zargar
- Advanced Center for Diabetes and Endocrine Care, Srinagar, India
| | - Shashank R Joshi
- Lilavati and Bhatia Hospital and Grant Medical College, Mumbai, India
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Hirose T, Awata T, Yamamoto Y, Hemmingsen MP. Clinical considerations for use of insulin degludec/insulin aspart in Japanese patients. Expert Opin Biol Ther 2017; 18:77-85. [PMID: 29017373 DOI: 10.1080/14712598.2018.1389888] [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: 10/18/2022]
Abstract
INTRODUCTION Co-formulation of basal and bolus insulin components provides a simpler regimen for patients with type 2 diabetes than separate basal-bolus treatment. However, conventional premixed insulin products include a suboptimal protaminated basal component that requires resuspension prior to injection. Insulin degludec/insulin aspart (IDegAsp) is the first soluble co-formulation of a basal insulin with an ultra-long duration of action (IDeg) and a rapid-acting bolus insulin (IAsp) in a single injection. AREAS COVERED In this review, the authors summarize findings from pre-clinical studies and the clinical trial program and provide guidance for the initiating and switching of IDegAsp in different patient populations. Pharmacodynamic analyses have revealed a rapid onset of action and distinct peak (IAsp), followed by a separate, flat and stable basal effect (IDeg component). Phase 3 studies have demonstrated the efficacy and safety of IDegAsp, with greater glycemic improvements than basal-only therapy in international and Japanese type 2 diabetes populations. IDegAsp also results in reduced insulin dose requirements and lower rates of hypoglycemia than premixed insulin. EXPERT OPINION IDegAsp provides a simple and effective insulin regimen in appropriately selected Japanese patients, with the flexibility to suit individual needs. The benefits of IDegAsp over conventional insulin regimens might help tackle clinical inertia with insulin intensification.
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Affiliation(s)
- Takahisa Hirose
- a Division of Diabetes, Metabolism and Endocrinology, Department of Medicine , Toho University School of Medicine , Tokyo , Japan
| | - Takuya Awata
- b Department of Diabetes, Endocrinology and Metabolism , International University of Health and Welfare Hospital , Tochigi , Japan
| | - Yuiko Yamamoto
- c Medical & Scientific Affairs Department , Novo Nordisk Pharma Ltd , Tokyo , Japan
| | - Mads Peter Hemmingsen
- d Medical & Scientific Affairs Department , Novo Nordisk Pharma Ltd ., Tokyo , Japan
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Onishi Y, Yamada K, Zacho J, Ekelund J, Iwamoto Y. Insulin degludec/insulin aspart vs biphasic insulin aspart 30 twice daily in Japanese patients with type 2 diabetes: A randomized controlled trial. J Diabetes Investig 2017; 8:210-217. [PMID: 27560769 PMCID: PMC5334300 DOI: 10.1111/jdi.12569] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Revised: 07/06/2016] [Accepted: 08/23/2016] [Indexed: 02/04/2023] Open
Abstract
AIMS/INTRODUCTION Insulin degludec/insulin aspart (IDegAsp) is a soluble combination of insulin degludec (70%) and insulin aspart (30%). The present exploratory trial investigated the safety of switching unit-to-unit from twice-daily basal or pre-mix insulin to twice-daily IDegAsp in Japanese patients with type 2 diabetes. MATERIALS AND METHODS In this 6-week, open-label, parallel-group, controlled trial, 66 participants were randomized (1:1) to receive either IDegAsp or biphasic insulin aspart 30 (BIAsp 30) twice daily at the same total daily dose as pre-trial insulin. During the trial, insulin doses were adjusted according to a pre-specified algorithm to achieve pre-breakfast and pre-dinner plasma glucose of 4.4-7.2 mmol/L. RESULTS No severe hypoglycemic episodes occurred. There were no statistically significant differences in rates of confirmed hypoglycemia (rate ratio IDegAsp/BIAsp 30: 0.63, 95% confidence interval: 0.31-1.30) and confirmed nocturnal hypoglycemia (rate ratio: 0.49, 95% confidence interval: 0.10-2.38) for IDegAsp vs BIAsp 30. The hypoglycemia rate for IDegAsp was constant over the 6 weeks of treatment. IDegAsp and BIAsp 30 were both safe and well tolerated. Reduction in fasting plasma glucose was statistically significantly greater for IDegAsp than for BIAsp 30 (estimated treatment difference, IDegAsp-BIAsp 30: -1.6 mmol/L, 95% confidence interval: -2.4 to -0.8). The apparent decrease in mean postprandial plasma glucose increment (IDegAsp: 4.2-3.8 mmol/L; BIAsp 30: 4.5-2.8 mmol/L) was not statistically significantly different between treatments (estimated treatment difference: 1.0 mmol/L, 95% confidence interval: -0.1 to 2.2). CONCLUSIONS Switching unit-to-unit from basal or pre-mix insulin to IDegAsp seems not to be associated with any concerns related to hypoglycemia or general safety in Japanese patients with type 2 diabetes.
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Affiliation(s)
- Yukiko Onishi
- The Institute for Adult DiseasesAsahi Life FoundationTokyoJapan
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48
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Taneda S, Hyllested-Winge J, Gall MA, Kaneko S, Hirao K. Insulin degludec/insulin aspart versus biphasic insulin aspart 30 twice daily in insulin-experienced Japanese subjects with uncontrolled type 2 diabetes: Subgroup analysis of a Pan-Asian, treat-to-target Phase 3 Trial. J Diabetes 2017; 9:243-247. [PMID: 27059529 DOI: 10.1111/1753-0407.12407] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 02/08/2016] [Accepted: 03/06/2016] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND The present study was a subgroup analysis of a Pan-Asian Phase 3 open-label randomized treat-to-target trial evaluating insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) in Japanese subjects with type 2 diabetes inadequately controlled on insulin. METHODS Eligible subjects (n = 178) were randomized (2: 1) to twice-daily (b.i.d.) IDegAsp or BIAsp 30 with or without metformin for 26 weeks, titrated to a blood glucose target of between 3.9 and <5.0 mmol/L. Changes in HbA1c , the proportion of responders reaching the HbA1c target, and changes in fasting plasma glucose, nine-point self-monitored plasma glucose profiles, and body weight were assessed. RESULTS At 26 weeks, the decrease in HbA1c was similar in both groups. Fasting plasma glucose was lower with IDegAsp than BIAsp 30 (estimated treatment difference -1.50 mmol/L; 95 % confidence interval [CI] -1.98, -1.01). Overall confirmed hypoglycemia rates were similar; the nocturnal confirmed hypoglycemia rate was lower with IDegAsp than BIAsp 30 (estimated rate ratio 0.44; 95 % CI 0.20, 0.99). No severe hypoglycemic episodes were reported. CONCLUSIONS The results indicate that IDegAsp b.i.d. improves glycemic control and, compared with BIAsp 30, lowers the rate of nocturnal confirmed hypoglycemia.
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Affiliation(s)
- Shinji Taneda
- Diabetes Center, Manda Memorial Hospital, Hokkaido, Japan
| | | | | | - Shizuka Kaneko
- Division of Diabetes, Endocrine and Lifestyle-related Disease, Takatsuki Red Cross Hospital, Osaka, Japan
| | - Koichi Hirao
- Department of Internal Medicine, HEC Science Clinic, Yokohama, Japan
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Park SW, Bebakar WMW, Hernandez PG, Macura S, Hersløv ML, de la Rosa R. Insulin degludec/insulin aspart once daily in Type 2 diabetes: a comparison of simple or stepwise titration algorithms (BOOST ® : SIMPLE USE). Diabet Med 2017; 34:174-179. [PMID: 26773557 PMCID: PMC5248615 DOI: 10.1111/dme.13069] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/11/2016] [Indexed: 12/17/2022]
Abstract
AIMS To compare the efficacy and safety of two titration algorithms for insulin degludec/insulin aspart (IDegAsp) administered once daily with metformin in participants with insulin-naïve Type 2 diabetes mellitus. METHODS This open-label, parallel-group, 26-week, multicentre, treat-to-target trial, randomly allocated participants (1:1) to two titration arms. The Simple algorithm titrated IDegAsp twice weekly based on a single pre-breakfast self-monitored plasma glucose (SMPG) measurement. The Stepwise algorithm titrated IDegAsp once weekly based on the lowest of three consecutive pre-breakfast SMPG measurements. In both groups, IDegAsp once daily was titrated to pre-breakfast plasma glucose values of 4.0-5.0 mmol/l. Primary endpoint was change from baseline in HbA1c (%) after 26 weeks. RESULTS Change in HbA1c at Week 26 was IDegAspSimple -14.6 mmol/mol (-1.3%) (to 52.4 mmol/mol; 6.9%) and IDegAspStepwise -11.9 mmol/mol (-1.1%) (to 54.7 mmol/mol; 7.2%). The estimated between-group treatment difference was -1.97 mmol/mol [95% confidence interval (CI) -4.1, 0.2] (-0.2%, 95% CI -0.4, 0.02), confirming the non-inferiority of IDegAspSimple to IDegAspStepwise (non-inferiority limit of ≤ 0.4%). Mean reduction in fasting plasma glucose and 8-point SMPG profiles were similar between groups. Rates of confirmed hypoglycaemia were lower for IDegAspStepwise [2.1 per patient years of exposure (PYE)] vs. IDegAspSimple (3.3 PYE) (estimated rate ratio IDegAspSimple /IDegAspStepwise 1.8; 95% CI 1.1, 2.9). Nocturnal hypoglycaemia rates were similar between groups. No severe hypoglycaemic events were reported. CONCLUSIONS In participants with insulin-naïve Type 2 diabetes mellitus, the IDegAspSimple titration algorithm improved HbA1c levels as effectively as a Stepwise titration algorithm. Hypoglycaemia rates were lower in the Stepwise arm.
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Affiliation(s)
| | | | - P. G. Hernandez
- Endocrinology ServiceHospital Universitario ‘Dr José E. González’MonterreyMéxico
| | - S. Macura
- Medical AffairsNovo Nordisk A/SSøborgDenmark
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Affiliation(s)
- Thomas Danne
- 1 Diabetes-Zentrum für Kinder and Jugendliche, Kinder- und Jugendkrankenhaus AUF DER BULT , Hannover, Germany
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