Effects of Once-Weekly Exenatide on Cardiovascular Outcomes
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Effects of Once-Weekly Exenatide on Cardiovascular Outcomes
Compared with placebo, this diabetes drug demonstrated neither harm nor significant benefit.
To satisfy regulatory requirements about showing cardiovascular (CV) safety of new diabetes medications, industry-sponsored researchers have conducted this randomized trial of once-weekly injected exenatide (Bydureon), a glucagon-like peptide-1 (GLP-1)-receptor agonist. Nearly 15,000 patients (mean age, 62) with longstanding type 2 diabetes received exenatide or placebo. During the trial, patients were permitted to use other diabetes drugs (oral agents and insulin). At baseline, about 70% of patients had experienced previous adverse CV events, and glycosylated hemoglobin (HbA1c) level averaged 8%.
During average follow-up of about 3 years, mean HbA1c levels changed little in the placebo group and dropped by roughly 0.5% in the exenatide group. The incidence of the primary CV outcome (CV-related death, myocardial infarction, or stroke) was 11.4% in the exenatide group and 12.2% in the placebo group. This difference met statistical criteria for exenatide’s noninferiority (for safety) but not superiority (for efficacy).
COMMENT
In this study, exenatide did not demonstrate CV harm, but it fell short of showing a statistically significant CV benefit. In contrast, another FDA-approved GLP-1 analogue (liraglutide) was associated with a significant 2 percentage-point reduction in adverse CV events during 4 years (NEJM JW Gen Med Jul 15 2016 and N Engl J Med 2016; 375:311). This apparent inconsistency might reflect intrinsically different CV effects of the two drugs or just differences in various aspects of the two trials.
Allan S. Brett, MD reviewing Holman RR et al. N Engl J Med 2017 Sep 28.
CITATION(S):
Holman RR et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2017 Sep 28; 377:1228. [PubMed® abstract]
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