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.
clinical trial, exenatide, glycaemic control, insulin pump therapy, phase III study, type 2 diabetes
Journal
Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
21
07
2020
revised:
02
10
2020
accepted:
07
10
2020
pubmed:
13
10
2020
medline:
6
7
2021
entrez:
12
10
2020
Statut:
ppublish
Résumé
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). 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. 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/m 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.
Substances chimiques
Blood Glucose
0
Glycated Hemoglobin A
0
Hypoglycemic Agents
0
Insulin
0
Venoms
0
Exenatide
9P1872D4OL
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
374-381Informations de copyright
© 2020 John Wiley & Sons Ltd.
Références
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.