Author ORCID Identifier

Salil V. Deo

Document Type

Article

Publication Date

5-1-2022

Abstract

Aims: To evaluate the time-varying cardio-protective effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) using pooled data from eight contemporary cardiovascular outcome trials using the difference in the restricted mean survival time (ΔRMST) as the effect estimate. Material and Methods: Data from eight multinational cardiovascular outcome randomized controlled trials of GLP-1RAs for type 2 diabetes mellitus were pooled. Flexible parametric survival models were fit from published Kaplan-Meier plots. The differences between arms in RMST (ΔRMST) were calculated at 12, 24, 36 and 48 months. ΔRMST values were pooled using an inverse variance-weighted random-effects model; heterogeneity was tested with Cochran's Q statistic. The endpoints studied were: three-point major adverse cardiovascular events (MACE), all-cause mortality, stroke, cardiovascular mortality and myocardial infarction. Results: We included eight large (3183-14 752 participants, total = 60 080; median follow-up range: 1.5 to 5.4 years) GLP-1RA trials. Among GLP-1RA recipients, we observed an average delay in three-point MACE of 0.03, 0.15, 0.37 and 0.63 months at 12, 24, 36 and 48 months, respectively. At 48 months, while cardiovascular mortality was comparable in both arms (pooled ΔRMST 0.163 [−0.112, 0.437]; P = 0.24), overall survival was higher (ΔRMST = 0.261 [0.08-0.43] months) and stroke was delayed (ΔRMST 0.22 [0.15-0.33]) in patients receiving GLP-1RAs. Conclusions: Glucagon-like peptide-1 receptor agonists may delay the occurrence of MACE by an average of 0.6 months at 48 months, with meaningfully larger gains in patients with cardiovascular disease. This metric may be easier for clinicians and patients to interpret than hazard ratios, which assume a knowledge of absolute risk in the absence of treatment.

Keywords

cardiovascular outcomes trials, clinical trials, GLP receptor agonist, systematic review, type II diabetes mellitus

Publication Title

Diabetes, Obesity and Metabolism: A Journal of Pharmacology and Therapeutics

Volume

24

Issue

8

First Page

1607

Last Page

1616

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

Comments

All datasets (data zip file) containing the information extracted from the published KM curves for each trial and all R code (rscript zip file) are avaialble from the corresponding author on reasonable request. They are also available for direct download from the corresponding authors github page - https://github.com/svd09/RMST_glp1a.

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