Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes.

UNLABELLED: It is important for patients that treatments for diabetes not increase cardiovascular (CV) risk. The objective of this analysis was to examine retrospectively the CV safety of exenatide BID, a GLP-1 receptor agonist approved for treating hyperglycemia in patients with type 2 diabetes not adequately controlled with diet and exercise. Individual participant data was pooled to assess the relative risk (RR) of CV events with exenatide BID versus a pooled comparator (PC) group treated with either placebo or insulin from 12 controlled, randomized, clinical trials ranging from 12-52 weeks. Mean baseline values for HbA1c (8.33-8.38%), BMI (31.3-31.5 kg/m2), and duration of diabetes (8 y) were similar between groups. Trials included patients with histories of microvascular and/or macrovascular disease. Customized primary major adverse CV events (MACE) included stroke, myocardial infarction, cardiac mortality, acute coronary syndrome, and revascularization procedures. The Primary MACE RR (0.7; 95% CI 0.38, 1.31), calculated by the Mantel-Haenszel method (stratified by study), suggested that exenatide use (vs. PC) did not increase CV risk; this result was consistent across multiple analytic methods. Because the trials were not designed to assess CV outcomes, events were identified retrospectively from a list of preferred terms by physicians blinded to treatment. Other limitations included the low number of CV events, the short duration of trials (≤1 y), and a single active comparator (insulin). The results of these analyses are consistent with those of a recent retrospective analysis of a large insurance database that found that patients treated with exenatide twice daily were less likely to have a CV event than were patients treated with other glucose-lowering therapies. KEYWORDS: GLP-1 receptor agonist, diabetes, cardiovascular safety.

Exenatide is non-inferior to insulin in reducing HbA1c: an integrated analysis of 1423 patients with type 2 diabetes.

OBJECTIVE: The objective was to compare the treatment effects between exenatide and insulin, which are 2 injectable peptide hormone-based therapy options for the treatment of type 2 diabetes mellitus. METHODS: Data from 4 randomized, open-label, comparator-controlled clinical trials in 1423 patients with type 2 diabetes followed for 16 to 52 weeks were pooled and analyzed. RESULTS: At 26 weeks, glycemic control with exenatide (-1.2% HbA1c) was non-inferior to insulin (-1.1%; exenatide vs insulin; P = 0.09). In a tertile analysis of HbA1c reduction from baseline, exenatide induced similar reductions compared with insulin, with the greatest reductions observed in the tertile with the highest baseline HbA1c (9%-12.7%). Exenatide treatment induced weight loss (-2 kg) and reduced systolic blood pressure (SBP) from baseline (SBP, -4.9 mm Hg, exenatide vs insulin; P < 0.0001). In contrast, insulin treatment increased body weight (1.8 kg) and decreased SBP by -0.4 mm Hg. Overall, about 3-fold more exenatide-treated patients (70%) experienced weight loss compared with those treated with insulin (21%). Occurrence of nocturnal mild-to-moderate hypoglycemia was lower with exenatide (15%) treatment than with insulin (29%; difference, -14; [95% CI, -18, -9.8]). Effects of exenatide on HbA1c and weight were sustained at 52 weeks. CONCLUSION: These findings indicate that exenatide is non-inferior to insulin for glycemic control. Further studies are warranted to explore the effects of exenatide on blood pressure and body weight, and the potential for long-term effects on cardiovascular outcomes.