Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes

N Engl J Med 2017;377:1228–39 DOI: 10.1056/NEJMoa1612917

The risk of all-cause death in people with T2D is up to twice that of the general population, and up to four-times that of the general population for the risk of death from CV causes. Glycaemic control clearly improves microvascular outcomes, but the effect on macrovascular outcomes is less certain. In line with regulatory guidance, the EXSCEL study assessed long-term CV safety and efficacy of once-weekly exenatide in T2D patients with a wide range of CV risk.

In EXSCEL, 14,752 patients with T2D – with or without previous CVD – were randomised to receive extended-release exenatide 2 mg or matching placebo once weekly. For the primary composite endpoint (first occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke), exenatide was noninferior to placebo with respect to safety, and was not superior to placebo with respect to efficacy. Over the 5 months of the study, there was a modest between-group difference in HbA1c, which may have influenced the difference in death rate. A modest effect was also seen on some other modifiable risk factors, including weight, systolic blood pressure, and lipids. The authors concluded that once-weekly exenatide in T2D patients at a wide range of CV risk appeared not to cause an increase in their overall CV risk.


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