Efficacy and safety of Exenatide as add‐on therapy for type 2 diabetes patients with intensive insulin regimen: a randomized double‐blind trial

AIMS A significant percentage of type 2 diabetes (T2D) patients remain uncontrolled despite treatment using intensified insulin regimens (IIR), leading diabetes physicians to consider further intensification. We assessed the safety and efficacy of the short-acting GLP-1RA exenatide on a population of T2D patients mostly treated with continuous subcutaneous insulin injection (CSII). MATERIALS AND METHODS Phase 2/3, multicenter, randomized, parallel groups, double blind, placebo-controlled 6-month trial. Patients were randomized to receive subcutaneous (SC) injections of exenatide (10μg 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% patients of exenatide and placebo groups, respectively. At 6 months: ΔHbA1c was -0.62±0.94 and 0.08±0.81% in exenatide and placebo groups, respectively (difference, -0.70; 95%Confidence Interval [-1.24 ; -0.15], p=0.014); body weight and BMI 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<0.001); the post-dinner capillary blood glucose value was lower in the exenatide group compared to the placebo group (162.4±80.5 vs 259.1±94.4 mg/dL, respectively; observed difference, -96.7, p<0.01). Hypoglycemic risk, quality of life and overall safety were not different between 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 10μg BID SC in T2D patients with uncontrolled HbA1c despite an IIR, resulted in a significant reduction of HbA1c and body weight with a good overall safety profile and acceptance. This article is protected by copyright. All rights reserved.