6/28/23, 10:09 PM EXSCEL Pathway Feedback Search Clinical Topics Home Studies EXSCEL EXSCEL Disease Diabetes mellitus type 2 Trial question What is the effect of once-weekly exenatide on cardiovascular outcome in patients with T2DM? Study design Multi-center Double blinded RCT Population Characteristics of study participants 38.0% female N = 14752 62.0% male 14752 patients (5603 female, 9109 male) Inclusion criteria: patients with T2DM, with or without previous CVD who are on medication Key exclusion criteria: history of 2 episodes of severe hypoglycemia during the preceding 12 months, end-stage kidney disease, personal or family history of medullary thyroid carcinoma or MEN2, or a previous treatment with a GLP-1 receptor agonist Interventions N=7356 exenatide (ER dose of 2 mg subcutaneous injection once weekly) N=7356 placebo (matching placebo once weekly) Primary outcome Death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke 12.2 % 12.2 11.4 9.1 % https://web.pathway.md/studies/reckie5LPKHF9T1QR 1/2 6/28/23, 10:09 PM EXSCEL Pathway 6.1 % Difference not exceeding nonferiority margin 3.0 % 0.0 % Exenatide Placebo Difference not exceeding nonferiority margin in death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (11.4% vs. 12.2%; HR 0.91, 95% CI 0.83 to 1) Secondary outcomes Significant decrease in death from any cause (6.9% vs. 7.9%; HR 0.86, 95% CI 0.77 to 0.97) No significant difference in death from cardiovascular causes (4.6% vs. 5.2%; HR 0.88, 95% CI 0.76 to 1.02) No significant difference in hospitalization for HF (3% vs. 3.1%; HR 0.94, 95% CI 0.78 to 1.13) Safety outcomes No significant difference in serious adverse events. Conclusion In patients with T2DM, with or without previous CVD who are on medication, exenatide was noninferior to placebo with respect to death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Reference Holman RR, Bethel MA, Mentz RJ et al. Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2017 Sep 28;377(13):1228-1239. Open reference URL https://web.pathway.md/studies/reckie5LPKHF9T1QR 2/2