Clinical Edge

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Effects of Exenatide on CV Outcomes in T2D

N Engl J Med; ePub 2017 Sep 14; Holman, et al

The incidence of major adverse cardiovascular (CV) events did not differ significantly between patients with type 2 diabetes (T2D) who received exenatide and those receiving placebo, a recent study found. Patients with T2D, with or without previous CVD, were randomly assigned to receive subcutaneous injections of extended-release exenatide (2 mg) or matching placebo once weekly. The primary composite outcome was first occurrence of death from CV causes, nonfatal myocardial infarction (MI), or nonfatal stroke. Researchers found:

  • 14,752 patients (10,782 [73%] with previous CVD) were followed for a median of 3.2 years.
  • A primary composite outcome event occurred in 839 of 7,356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7,396 patients (12.2%; 4.0 events per 100 patient-years) in the placebo group (HR, 0.91).
  • Rates of death from CV causes, fatal or nonfatal MI, fatal or nonfatal stroke, hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the 2 groups.


Holman RR, Bethel A, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. [Published online ahead of print September 14, 2017]. N Engl J Med. doi:10.1056/NEJMoa1612917.


Medications from two classes of medications, SGLT-2s and GLP-1 receptor agonists, have been shown to decrease major adverse cardiovascular events in patients with diabetes and established cardiovascular disease.1,2,3,4 Some medications in these classes, specifically lixisenatide and now exenatide, have been shown to have safe cardiovascular profiles but did not show a reduction in CV outcomes in the studies performed. Whether this difference is because of differences in the individual medications' effects or the fact that the medications that did not show benefit were studied in lower risk populations with a lower prevalence of established CV disease and therefore a lower total event rate, is unknown. Importantly, all SGLT-2s and all GLP-1 RAs studied have shown unequivocal CV safety. —Neil Skolnik, MD

  1. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322. doi:10.1056/NEJMoa1603827.
  2. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128. doi:10.1056/NEJMoa1504720.
  3. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. [Published online ahead of print June 12, 2017]. N Engl J Med.
  4. Marso SP, et al.Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-1844. doi:10.1056/NEJMoa1607141.