Efficacy and safety of exenatide as add-on therapy for patients with type 2 diabetes with an intensive insulin regimen: A randomized double-blind trial
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem
PubMed
33043591
DOI
10.1111/dom.14225
Knihovny.cz E-zdroje
- Klíčová slova
- clinical trial, exenatide, glycaemic control, insulin pump therapy, phase III study, type 2 diabetes,
- MeSH
- diabetes mellitus 2. typu * farmakoterapie MeSH
- dvojitá slepá metoda MeSH
- exenatid MeSH
- glykovaný hemoglobin analýza MeSH
- hypoglykemika škodlivé účinky MeSH
- inzulin MeSH
- krevní glukóza MeSH
- kvalita života MeSH
- lidé MeSH
- výsledek terapie MeSH
- živočišné jedy škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- exenatid MeSH
- glykovaný hemoglobin MeSH
- hypoglykemika MeSH
- inzulin MeSH
- krevní glukóza MeSH
- živočišné jedy MeSH
AIM: To assess the safety and efficacy of the short-acting glucagon-like peptide-1 receptor agonist exenatide on a population of patients with type 2 diabetes (T2D) mostly treated with continuous subcutaneous insulin injection (CSII). MATERIALS AND METHODS: A phase 2/3, multicentre, randomized, parallel-group, double-blind, placebo-controlled, 6-month trial was conducted. Patients were randomized to receive subcutaneous (SC) injections of exenatide (10 μg BID) or matched placebo. RESULTS: A total of 46 patients with T2D and elevated HbA1c were randomized (42% of the planned sample size): exenatide (n = 28) and placebo (n = 18). CSII treatment was used by 75% and 89% of patients of the exenatide and placebo groups, respectively. At 6 months, the change in HbA1c was -0.62% ± 0.94% and 0.08% ± 0.81% in the exenatide and placebo groups, respectively (difference, -0.70%; 95% CI [-1.24%; -0.15%], P = .014); body weight and body mass index decreased in the exenatide group (-2.55 ± 3.25 kg and -1.00 ± 1.31 kg/m2 ) and increased in the placebo group (1.29 ± 2.82 kg and 0.46 ± 1.16 kg/m2 ) (observed difference, -3.85 and -1.45, respectively, both P < .001); the postdinner capillary blood glucose value was lower in the exenatide group compared with the placebo group (162.4 ± 80.5 vs. 259.1 ± 94.4 mg/dL, respectively; observed difference, -96.7, P < .01). Hypoglycaemic risk, quality of life and overall safety were not different between the groups, apart from the expected occurrence of digestive effects in the exenatide group. CONCLUSIONS: Although we failed to reach our planned sample size, the addition of exenatide treatment 10 μg BID SC in T2D patients with uncontrolled HbA1c despite an intensified insulin regimen, resulted in a significant reduction of HbA1c and body weight with a good overall safety profile and acceptance.
1st Department of Internal Medicine Charles University Hospital in Pilsen Pilsen Czech Republic
Charles University Faculty of Medicine in Pilsen Pilsen Czech Republic
Clinical Research Unit Caen University Hospital Caen France
Diabetes Care Unit Caen University Hospital Caen France
Diabetes Care Unit Strasbourg University Hospital Strasbourg France
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Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of diabetes (EASD). Diabetologia. 2018;61:2461-2498.
Giugliano D, Chiodini P, Maiorino MI, Bellastella G, Esposito K. Intensification of insulin therapy with basal-bolus or premixed insulin regimens in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Endocrine. 2016;51:417-428.
Anyanwagu U, Mamza J, Gordon J, Donnelly R, Idris I. Premixed vs basal-bolus insulin regimen in type 2 diabetes: comparison of clinical outcomes from randomized controlled trials and real-world data. Diabet Med. 2017;34:1728-1736.
Wang C, Mamza J, Idris I. Biphasic vs basal bolus insulin regimen in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Diabet Med. 2015;32:585-594.
Pickup JC, Reznik Y, Sutton AJ. Glycemic control during continuous subcutaneous insulin infusion versus multiple daily insulin injections in type 2 diabetes: individual patient data meta-analysis and meta-regression of randomized controlled trials. Diabetes Care. 2017;40:715-722.
Reznik Y, Cohen O, Aronson R, et al. Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial. Lancet. 2014;384:1265-1272.
Ostergaard L, Frandsen CS, Madsbad S. Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review. Exp Rev Clin Pharmacol. 2016;9:241-265.
Pontiroli AE, Miele L, Morabito A. Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: systematic review and meta-analysis. Diabetes Obes Metab. 2011;13:1008-1019.
Giugliano D, Maiorino MI, Bellastella G, Longo M, Chiodini P, Esposito K. GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: an updated meta-analysis including the REWIND and PIONEER 6 trials. Diabetes Obes Metab. 2019;21:2576-2580.
Dalsgaard NB, Vilsboll T, Knop FK. Effects of glucagon-like peptide-1 receptor agonists on cardiovascular risk factors: a narrative review of head-to-head comparisons. Diabetes Obes Metab. 2018;20:508-519.
Owens DR, Monnier L, Bolli GB. Differential effects of GLP-1 receptor agonists on components of dysglycaemia in individuals with type 2 diabetes mellitus. Diabetes Metab. 2013;39:485-496.
Mannucci E, Monami M, Lamanna C, Adalsteinsson JE. Post-prandial glucose and diabetic complications: systematic review of observational studies. Acta Diabetol. 2012;49:307-314.
Lane W, Weinrib S, Rappaport J, Hale C. The effect of addition of liraglutide to high-dose intensive insulin therapy: a randomized prospective trial. Diabetes Obes Metab. 2014;16:827-832.
Lind M, Hirsch IB, Tuomilehto J, et al. Liraglutide in people treated for type 2 diabetes with multiple daily insulin injections: randomised clinical trial (MDI Liraglutide trial). BMJ. 2015;351:h5364.
de Wit HM, Vervoort GM, Jansen HJ, et al. Liraglutide reverses pronounced insulin-associated weight gain, improves glycaemic control and decreases insulin dose in patients with type 2 diabetes: a 26 week, randomised clinical trial (ELEGANT). Diabetologia. 2014;57:1812-1819.
Li FF, Jiang L, Fu L, et al. Exenatide add-on to continuous subcutaneous insulin infusion therapy reduces bolus insulin doses in patients with type 2 diabetes: a randomized, controlled, open-label trial. Diabetes Ther. 2017;8:177-187.
Phillips LK, Deane AM, Jones KL, Rayner CK, Horowitz M. Gastric emptying and glycaemia in health and diabetes mellitus. Nat Rev Endocrinol. 2015;11:112-128.
Reznik Y, Habteab A, Castaneda J, Shin J, Joubert M. Contribution of basal and postprandial hyperglycaemia in type 2 diabetes patients treated by an intensified insulin regimen: impact of pump therapy in the OPT2mise trial. Diabetes Obes Metab. 2018;20:2435-2441.
Ogawa S, Nako K, Okamura M, Sakamoto T, Ito S. Stabilization of postprandial blood glucose fluctuations by addition of glucagon like polypeptide-analog administration to intensive insulin therapy. J Diabetes Investig. 2015;6:436-442.
Maloney A, Rosenstock J, Fonseca V. A model-based meta-analysis of 24 antihyperglycemic drugs for type 2 diabetes: comparison of treatment effects at therapeutic doses. Clin Pharmacol Ther. 2019;105:1213-1223.