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Cited by 99Diabetes Treatment and ManagementHeart Failure Treatment and ManagementCardiovascular Function and Risk Factors

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

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Fudim, Marat, White, Jennifer, Pagidipati, Neha J., Lokhnygina, Yuliya, Wainstein, Julio, Murin, Jan, Iqbal, Nayyar, Öhman, Peter +5 more·2019·Circulation
DOI 10.1161/circulationaha.119.041659PMC PMC6924268
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Abstract

Background: Once-weekly exenatide (EQW) had a neutral effect on hospitalization for heart failure (HHF) in the EXSCEL study (Exenatide Study of Cardiovascular Event Lowering), with no differential treatment effect on major adverse cardiac events by baseline heart failure (HF) status. EQW’s effects on secondary end points based on HHF status have not been reported. The objective was to explore the effects of EQW on secondary end points 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 mellitus with and without additional cardiovascular disease, analyzed EQW effects on all-cause death, each major adverse cardiac event 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, and more likely to be male and white, with a higher burden of other cardiovascular diseases. Overall, those assigned to EQW had a lower incidence of all-cause death (hazard ratio [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. The 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: https://www.clinicaltrials.gov . Unique identifier: NCT01144338.

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Authors
Fudim, M., White, J., Pagidipati, N. J., Lokhnygina, Y., Wainstein, J., Murin, J., Iqbal, N., Öhman, P., Lopes, R. D., Reicher, B., Holman, R. R., Hernandez, A. F., & Mentz, R. J.
Affiliations
  • Duke University (US)
  • Tel Aviv University (IL)
  • University Hospital, Bratislava, Slovakia (J.M.).
  • AstraZeneca Research and Development, Gaithersburg, MD (N.I., P.Ö., B.R.).
  • Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (M.F., J.W., N.J.P., Y.L., R.D.L., A.F.H., R.J.M.).
  • University of Oxford (GB)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2019-11-12
Volume
140
Issue
20
Pages
1613-1622
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.119.041659
PMC
PMC6924268
OpenAlex
W2985002379
Cited by
99
References
38
Citations by year
2026: 10 · 2025: 19 · 2024: 14 · 2023: 15 · 2022: 17 · 2021: 10 · 2020: 12 · 2019: 1 · 2017: 1
FWCI
8.11
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Heart, Lung, and Blood Institute (K12HL138030, T32HL007101)
  • Duke Clinical Research Institute
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
exenatide, type 2 diabetes, heart failure, heart failure hospitalization, major adverse cardiac events, all-cause mortality, EXSCEL trial, subgroup analysis, ejection fraction, GLP-1 receptor agonists, cardiovascular outcomes, treatment effect heterogeneity, cardiovascular disease burden, heart failure with preserved ejection fraction
MeSH terms
Exenatide, Aged, Cause of Death, Diabetes Mellitus, Type 2, Drug Administration Schedule, Female, Heart Failure, Humans, Hypoglycemic Agents, Male, Middle Aged, Patient Admission, Risk Factors, Time Factors, Treatment Outcome, Disease Progression, Incretins

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