Effect of Once-Weekly Exenatide in Patients With Type 2 Diabetes With and Without Heart Failure and Heart Failure-Related Outcomes: Insights From the EXSCEL Trial.

Published online

Journal Article

Background: Once-weekly exenatide (EQW) had a neutral effect on hospitalization for heart failure (hHF) in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL), with no differential treatment effect on major adverse cardiac events (MACE) by baseline heart failure (HF) status. EQW's effects on secondary endpoints based on hHF status have not been reported. The objective was to explore the effects of EQW on secondary endpoints in patients with and without baseline HF and test the effects of EQW on recurrent hHF events. Methods: The prespecified analysis of the randomized controlled EXSCEL trial, which enrolled patients with type 2 diabetes with and without additional cardiovascular disease, analyzed EQW effects on all-cause death, each MACE component, first hHF and repeat hHF by baseline HF status (regardless of ejection fraction). A subgroup analysis of the population stratified by preserved or reduced baseline ejection fraction was performed. Results: Of 14,752 EXSCEL participants, 2389 (16.2%) had HF at baseline. Compared with those without HF at baseline, patients with preexisting HF were older, more likely to be male and White, and with a higher burden of other cardiovascular diseases. Overall, those assigned to EQW had a lower incidence of all-cause death (HR 0.86, 95%CI 0.77-0.97) and the composite outcome of all-cause death or hHF (HR 0.89, 95%CI 0.80-0.99). When stratified by presence or absence of baseline HF, there was no observed reduction in all-cause death with EQW with baseline HF (HR 1.05, 95%CI 0.85-1.29), while the risk of mortality was reduced with EQW in the no-HF group (HR 0.79, 95%CI 0.68-0.92) with an interaction p-value of 0.031. Reduction in all-cause death or hHF seen with EQW in patients without baseline HF (HR 0.81, 95%CI 0.71-0.93) was not seen in patients with baseline HF (HR 1.07, 95%CI 0.89-1.29) (interaction p=0.015). First plus recurrent hHF was reduced in the exenatide group versus placebo (HR 0.82, 95%CI 0.68-0.99; p=0.038). Conclusions: In EXSCEL, the use of EQW in patients with or without HF was well tolerated, but benefits of EQW on reduction in all-cause death and first hospitalization for HF were attenuated in patients with baseline HF. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01144338.

Full Text

Duke Authors

Cited Authors

  • Fudim, M; White, J; Pagidipati, NJ; Lokhnygina, Y; Wainstein, J; Murin, J; Iqbal, N; Öhman, P; Lopes, RD; Reicher, B; Holman, RR; Hernandez, AF; Mentz, RJ

Published Date

  • September 23, 2019

Published In

PubMed ID

  • 31542942

Pubmed Central ID

  • 31542942

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/CIRCULATIONAHA.119.041659


  • eng

Conference Location

  • United States