Effects of glucagon‐like peptide‐1 receptor agonists on cardiovascular and renal outcomes: A meta‐analysis and meta‐regression analysis
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Abstract
Aim: To evaluate the cardiovascular and renal outcomes of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and the associations between these outcomes and HbA1c or weight reduction. Materials and Methods: We searched PubMed/MEDLINE, EMBASE, and CENTRAL databases for randomized, placebo‐controlled trials of GLP‐1 RAs reporting major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, stroke, and myocardial infarction) as the primary outcome. We conducted a meta‐regression analysis of primary and secondary outcomes with HbA1c or weight reduction following a meta‐analysis with a random‐effects model for these outcomes. Results: We extracted data of 60 800 individuals from eight eligible studies (ELIXA, LEADER, SUSTAIN‐6, EXSCEL, HARMONY, PIONEER 6, REWIND, and AMPLITUDE‐O). GLP‐1 RAs reduced MACE (hazard ratio [HR] 0.86; 95% CI: 0.80‐0.93; P < .001) and secondary outcomes including the composite renal outcome (0.80; 0.73‐0.87; P < .001). In meta‐regression analysis, every 1% reduction in HbA1c was associated with 26% and 35% decreases in the logarithm of HR of MACE ( P = .044; R 2 = 0.65) and the composite renal outcome ( P = .040; R 2 = 0.85), respectively. On the contrary, weight reduction was not associated with any outcome, including MACE ( P = .390). Conclusions: The reduction in HbA1c, but not body weight, is associated with cardiovascular and renal outcomes. The magnitude of HbA1c reduction can be a surrogate for the cardiovascular and renal benefits of treatment with GLP‐1 RAs.
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The cardioprotective impact of GLP-1RA therapy is established with several large cardiovascular outcome trials demonstrating clear benefits and suggest a class effect.
“The cardioprotective impact of GLP-1RA therapy is now established with several large cardiovascular outcome trials demonstrating clear benefits and together strongly suggest a class effect of GLP-1RA therapy.11,12”
From Randomised trial comparing weight loss through lifestyle and GLP-1 receptor agonist therapy in people with MASLD (2025) · cites this paper as [12]
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- Authors
- Yoshiji, S., Minamino, H., Tanaka, D., Yamane, S., Harada, N., & Inagaki, N.
- Affiliations
- Japan Society for the Promotion of Science (JP)
- Kyoto University (JP)
- Corresponding author
- Inagaki, Nobuya
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2022-02-21
- Volume
- 24
- Issue
- 6
- Pages
- 1029-1037
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W4211100132
- Semantic Scholar
- 1d1ded61b6547db4a53f48d338a219a8f277dedd
- Cited by
- 40
- References
- 40
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 10 · 2023: 10 · 2022: 5
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nd)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (20K08903, 22KJ1696, 21K08527)
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- GLP-1 receptor agonists, major adverse cardiovascular events, renal outcomes, HbA1c reduction, weight loss, type 2 diabetes, cardiovascular risk prediction, surrogate endpoints
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Regression Analysis, Weight Loss, Glucagon-Like Peptide 1
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