REVIEW PAPER
Figure from article: Cardiovascular effects of...
 
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
Cardiovascular disease (CVD) is a major cause of morbidity and mortality, especially in type 2 diabetes mellitus (T2DM). Selected glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide cardiovascular benefit beyond glucose lowering. The aim of the review is to summarize compound-specific cardiovascular evidence and data in obesity, heart failure with preserved ejection fraction (HFpEF), and chronic kidney disease (CKD).

Review methods:
A narrative review used PubMed, Scopus, and supplementary Google Scholar searches from database inception to 6 August 2026, with reference to SANRA. Landmark cardiovascular outcome trials (CVOTs), randomized trials, meta-analyses, guidelines, and selected mechanistic studies were included. Thirty-two publications were analyzed.

Brief description of the state of knowledge:
CVOTs show heterogeneous results across GLP-1RAs, ranging from cardiovascular safety to reductions in major adverse cardiovascular events (MACE). SELECT demonstrated secondary-prevention benefit with semaglutide 2.4 mg in adults with overweight or obesity, without diabetes, but with established cardiovascular disease. In obesity-related HFpEF, semaglutide improved symptoms, physical function, and body weight, while effects on mortality and heart-failure hospitalization remain uncertain. Kidney benefits are supported by pooled analyses and FLOW. Gastrointestinal and biliary adverse effects remain relevant safety considerations.

Summary:
GLP-1RAs reduce cardiovascular risk in selected patients with T2DM, but effects are not uniform across the class. Evidence beyond T2DM remains compound- and population-specific, and further studies should clarify long-term safety, hard heart-failure outcomes, comparative effectiveness, and optimal patient selection.
REFERENCES (33)
1.
American Diabetes Association Professional Practice Committee for Diabetes. 10. Cardiovascular disease and risk management: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(Suppl 1):S216–S245. doi:10.2337/dc26-S010.
 
2.
Marx N, Federici M, Schütt K, et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023;44:4043–4140. doi:10.1093/eurheartj/ehad192.
 
3.
Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes—state-of-the-art. Mol Metab. 2021;46:101102. doi:10.1016/j.molmet.2020.101102.
 
4.
Ansari HUH, Qazi SU, Sajid F, et al. Efficacy and safety of glucagon- like peptide-1 receptor agonists on body weight and cardiometabolic parameters in individuals with obesity and without diabetes: a systematic review and meta-analysis. Endocr Pract. 2024;30(2):160–171. doi:10.1016/j.eprac.2023.11.007.
 
5.
Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9:653–662. doi:10.1016/S2213-8587(21)00203-5.
 
6.
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221–2232. doi:10.1056/NEJMoa2307563.
 
7.
Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389:1069–1084. doi:10.1056/NEJMoa2306963.
 
8.
Kosiborod MN, Petrie MC, Borlaug BA, et al. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. N Engl J Med. 2024;390:1394–1407. doi:10.1056/NEJMoa2313917.
 
9.
Butler J, Shah SJ, Petrie MC, et al. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet. 2024;403:1635–1648. doi:10.1016/S0140-6736(24)00469-0.
 
10.
Badve SV, Bilal A, Lee MMY, et al. Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2025;13:15–28. doi:10.1016/S2213-8587(24)00271-7.
 
11.
Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391:109–121. doi:10.1056/NEJMoa2403347.
 
12.
Baethge C, Goldbeck-Wood S, Mertens S. SANRA—a scale for the quality assessment of narrative review articles. Res Integr Peer Rev. 2019;4:5. doi:10.1186/s41073-019-0064-8.
 
13.
Marx N, Husain M, Lehrke M, Verma S, Sattar N. GLP-1 receptor agonists for the reduction of atherosclerotic cardiovascular risk in patients with type 2 diabetes. Circulation. 2022;146:1882–1894. doi:10.1161/CIRCULATIONAHA.122.059595.
 
14.
Park B, Bakbak E, Teoh H, et al. GLP-1 receptor agonists and atherosclerosis protection: the vascular endothelium takes center stage. Am J Physiol Heart Circ Physiol. 2024;326(5):H1159–H1176. doi:10.1152/ajpheart.00574.2023.
 
15.
Helmstädter J, Frenis K, Filippou K, et al. Endothelial GLP-1 receptor mediates cardiovascular protection by liraglutide in mice with experimental arterial hypertension. Arterioscler Thromb Vasc Biol. 2020;40:145–158. doi:10.1161ATV.0000615456.97862.30.
 
16.
Baggio LL, Drucker DJ. Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. Mol Metab. 2021;46:101090. doi:10.1016/j.molmet.2020.101090.
 
17.
Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27:740–756. doi:10.1016/j.cmet.2018.03.001.
 
18.
Battistoni A, Piras L, Tartaglia N, et al. Glucagon-like peptide-1 receptor agonists and the endothelium: molecular and clinical insights into cardiovascular protection. Front Med. 2025;12:1669685. doi:10.3389/fmed.2025.1669685.
 
19.
Chen JY, Hsu TW, Liu JH, et al. Kidney and cardiovascular outcomes among patients with CKD receiving GLP-1 receptor agonists: a systematic review and meta-analysis of randomized trials. Am J Kidney Dis. 2025;85:555–569.e1. doi:10.1053/j.ajkd.2024.11.013.
 
20.
Sattar N, McGuire DK. Pathways to cardiorenal complications in type 2 diabetes mellitus: a need to rethink. Circulation. 2018;138:7–9. doi:10.1161/CIRCULATIONAHA.118.035083.
 
21.
Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373:2247–2257. doi:10.1056/NEJMoa1509225.
 
22.
Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–322. doi:10.1056/NEJMoa1603827.
 
23.
Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–1844. doi:10.1056/NEJMoa1607141.
 
24.
Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J.Med. 2017;377:1228–1239. doi:10.1056/NEJMoa1612917.
 
25.
Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018;392:1519–1529.doi:10.1016/S0140-6736(18)32261-X.
 
26.
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394:121–130. doi:10.1016/S0140-6736(19)31149-3.
 
27.
Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med.2019;381:841–851. doi:10.1056/NEJMoa1901118.
 
28.
Gerstein HC, Sattar N, Rosenstock J, et al. Cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes. N Engl J Med. 2021;385:896–907. doi:10.1056/NEJMoa2108269.
 
29.
McGuire DK, Marx N, Mulvagh SL, et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. N Engl J Med. 2025;392:2001–2012. doi:10.1056/NEJMoa2501006.
 
30.
Giugliano D, Maiorino MI, Bellastella G, et al. GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: an updated meta-analysis including the REWIND and PIONEER 6 trials. Diabetes Obes Metab. 2019;21:2576–2580.doi:10.1111dom.13847.
 
31.
Kalayci A, Januzzi JL Jr, Mitsunami M, et al. Clinical features modifying the cardiovascular benefits of GLP-1 receptor agonists: a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother. 2025;11:552–561. doi:10.1093/ehjcvp/pvaf037.
 
32.
Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagonlike peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019;139:2022–2031. doi:10.1161/CIRCULATIONAHA.118.038868.
 
33.
Galli M, Benenati S, Laudani C, et al. Cardiovascular effects and tolerability of GLP-1 receptor agonists: a systematic review and metaanalysis of 99,599 patients. J Am Coll Cardiol. 2025;86(20):1805–1819. doi:10.1016/j.jacc.2025.08.027.
 
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