Are the cardiovascular properties of GLP-1 receptor agonists differentially modulated by sulfonylureas? Insights from post-hoc analysis of EXSCEL
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Authors
Gooding, K. M.
Stevens, S.
Lokhnygina, Y.
Giczewska, A.
Shore, A. C.
Holman, R. R.
Issue Date
2024-06-01
Type
Randomized Controlled Trial
Language
eng
Keywords
Humans , *Sulfonylurea Compounds/therapeutic use , *Hypoglycemic Agents/therapeutic use , *Glucagon-Like Peptide-1 Receptor/agonists , Male , Female , Middle Aged , *Cardiovascular Diseases , *Diabetes Mellitus, Type 2/drug therapy , *Exenatide/therapeutic use , Aged , Peptides/therapeutic use , Glucagon-Like Peptide-1 Receptor Agonists , Cardiovascular outcomes , GLP-1 RAs , Sulfonylurea , Type 2 diabetes
Alternative Title
AIMS: To examine whether the cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are attenuated by concurrent sulfonylurea (SU) therapy in a post-hoc analysis of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). METHODS: We investigated whether SUs, as a class or by specific type, modulated the effects of once-weekly exenatide (EQW) on EXSCEL cardiovascular outcomes in intent-to-treat analyses of all trial participants, categorized as SU users or nonusers. Marginal structural models were used to evaluate whether there were differential EQW effects by SU category on major adverse cardiovascular events (MACE), depending on duration of SU use (6, 12, and 18 months). EQW-by-SU type interaction p-values and hazard ratios (95 % CIs) for EQW versus placebo for each baseline SU type (glibenclamide, gliclazide, glimepiride, other SUs) were calculated. RESULTS: Neither SU use nor baseline SU type modified the effect of EQW on time to MACE (p(interaction) = 0.88 and 0.78, respectively), nor did individual SU types, including glibenclamide (a systemically wide-acting SU). CONCLUSIONS: SUs did not modulate the effect of EQW on cardiovascular outcomes, suggesting that SU treatment choices need not be altered to optimize the cardiovascular effects of GLP-1 receptor agonists in people with type 2 diabetes.
Description
Citation
Gooding KM, Stevens S, Lokhnygina Y, Giczewska A, Shore AC, Holman RR. Are the cardiovascular properties of GLP-1 receptor agonists differentially modulated by sulfonylureas? Insights from post-hoc analysis of EXSCEL. Diabetes Res Clin Pract. 2024;212:111685.
Publisher
Elsevier
License
© 2024 The Authors. Published by Elsevier B.V. All rights reserved.
Journal
Diabetes research and clinical practice