GLP-1 Receptor Agonist Therapy With and Without SGLT2 Inhibitors in Patients With Type 2 Diabetes
- PMID: 37532422
- DOI: 10.1016/j.jacc.2023.05.048
GLP-1 Receptor Agonist Therapy With and Without SGLT2 Inhibitors in Patients With Type 2 Diabetes
Abstract
Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP-1 RAs) reduce adverse cardiovascular outcomes in type 2 diabetes (T2D). However, the efficacy of combination therapy is unclear.
Objectives: The aim of this study was to evaluate the effects of GLP-1 RAs on cardiovascular outcomes in patients with T2D treated with or without SGLT2 inhibitors.
Methods: Post hoc analysis of Harmony Outcomes (Albiglutide and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease) evaluating the effect of albiglutide in T2D with cardiovascular disease by background SGLT2 inhibitor use. Additionally, a trial-level meta-analysis of Harmony Outcomes and AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes), which evaluated T2D with cardiovascular or renal disease, was performed, combining the treatment effect estimates according to SGLT2 inhibitor use.
Results: Of the 9,462 participants in Harmony Outcomes, 575 (6.1%) were treated with SGLT2 inhibitors at baseline. The effect of albiglutide on reducing the composite of cardiovascular death, myocardial infarction, or stroke (major adverse cardiovascular events) was consistent with or without SGLT2 inhibitors (P interaction = 0.70). The effect of albiglutide on secondary outcomes and adverse events was not modified by SGLT2 inhibitors. A meta-analysis of Harmony Outcomes and AMPLITUDE-O included 13,538 patients, of whom 1,193 (8.8%) used SGLT2 inhibitors. Compared to placebo, GLP1-RAs reduced major adverse cardiovascular events without effect modification by SGLT2 inhibitor use (HR: 0.77; 95% CI: 0.68-0.87 without SGLT2 inhibitors; and HR: 0.78; 95% CI: 0.49-1.24 with SGLT2 inhibitors) (P for interaction = 0.95) and reduced heart failure hospitalization (HR: 0.72; 95% CI: 0.55-0.92 vs HR: 0.34; 95% CI: 0.12-0.96) (P for interaction = 0.18).
Conclusions: In patients with T2D and cardiovascular disease, GLP-1 RAs reduced cardiovascular events independently of SGLT2 inhibitor use. These findings suggest that the combination of GLP-1 RAs with SGLT2 inhibitors may further reduce cardiovascular risk. Clinical trials with combination therapy are needed.
Keywords: GLP-1 receptor agonist; SGLT2 inhibitor; cardiovascular disease; heart failure; type 2 diabetes.
Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Conflict of interest statement
Funding Support and Author Disclosures This study was supported by national funds through Fundação para a Ciência e a Tecnologia, I.P., under the scope of the Cardiovascular R&D Center-Cardiovascular R&D Unit (UIDB/00051/2020 and UIDP/00051/2020). Dr Neves has received consulting or speaker fees from AstraZeneca, BIAL, Boehringer Ingelheim, Lilly, Merck, and Novo Nordisk. Dr Borges Canha has received speaker fees from AstraZeneca and Medinfar. Dr Green has received institutional grant funding from Boehringer Ingelheim–Lilly, Merck, Roche, and Sanofi and Lexicon; and has received consultancy fees from Boehringer Ingelheim–Lilly, Bayer, AstraZeneca, Sanofi and Lexicon, Hawthorne Effect and Omada, Pfizer, Valo, Anji, Vertex, and Novo Nordisk. Dr Leiter has received research funding from, has provided continuing medical education on behalf of, and/or has acted as an advisor to AstraZeneca, Boehringer Ingelheim, Eli Lilly, GSK, Lexicon, Merck, Novo Nordisk, Pfizer, Sanofi, and Servier. Dr Granger has received research grants from AKROS, Apple, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Duke Clinical Research Institute, the U.S. Food and Drug Administration, GlaxoSmithKline, Janssen Pharmaceutical Products, LP, Medtronic Foundation, Novartis Pharmaceuticals, and Pfizer; and has received consulting fees from AbbVie, Abiomed, Anthos Therapeutic, LLC, Bayer Corporation, Boehringer Ingelheim, Boston Scientific Corporation, Bristol Myers Squibb, CeleCor Therapeutics, Correvio, Espero BioPharma, Janssen Pharmaceutica Products, LP, Medscape, LLC, Medtronic Inc, Merck, Novo Nordisk, Novartis Pharmaceutical Company, Pfizer, Phillips, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr Carvalho has received consulting or speaker fees from AstraZeneca, BIAL, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck, Merck Co, Medinfar, Novo Nordisk, and Sanofi. Dr Hernandez has received grants from Amgen, Bayer, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Pfizer and Verily; and has received consulting fees from AstraZeneca, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis Pharmaceuticals, and Novo Nordisk. Dr Del Prato has received grants from AstraZeneca and Boehringer Ingelheim; has received consulting fees from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hengrui Pharmaceuticals Co, Menarini International, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk, and Sanofi; and has received honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk, and Sanofi. Dr McMurray has received institutional grant funding from AstraZeneca; has received consultancy fees from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Heart.Org (Medscape Cardiology), ProAdWise Communications, Radcliffe Cardiology, Servier, and The Corpus; and has received fees paid to his institution for other advisory roles by Cytokinetics, Amgen, AstraZeneca, Theracos, Ionis Pharmaceuticals, DalCor, Cardurion, Novartis, GlaxoSmithKline, Bayer, KBP Biosciences, Boehringer Ingelheim, and Bristol Myers Squibb. Dr Ferreira is a consultant for Boehringer Ingelheim; and has received research support from AstraZeneca and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Comment in
-
GLP-1 RA and SGLT2 Inhibitors: In Harmony for Organ Protection.J Am Coll Cardiol. 2023 Aug 8;82(6):526-528. doi: 10.1016/j.jacc.2023.06.005. J Am Coll Cardiol. 2023. PMID: 37532423 No abstract available.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
