Current issue
Archive
About the Journal
Instructions for authors
1/2026 vol. 11
Stats
Get citation
SYSTEMATIC REVIEW
Figure from article: GLP-1 receptor agonists in...
GLP-1 receptor agonists in cardiometabolic disease: a meta-analysis of 102,486 patients
Zena Adel Alwaily 1
,
 
Obaid Ur Rahman 2
,
 
Aung Thet Swe 3
,
 
Aya Abouayana 4
,
 
Navdeep Singh Sodhi 5
,
 
Mei Jia Goh 6
,
 
Adeel Ahmed 7
,
 
Tharun Adithya Natesan 8
,
 
Shahzaib Shahzad 9
,
 
Om Harsh Merchant 10
,
 
Yumna Aziz Khan 11
,
 
Muhammad Farooq 12
,
 
Maryam Shahzad 13
,
 
Gabriele Volucke 14
 
 
 
More details
Hide details
1
Department of Geriatrics, NHS Ayrshire and Arran, University Hospital Ayr, United Kingdom
 
2
Department of Cardiology, University Hospital North Midlands (UHNM) NHS Trust, United Kingdom
 
3
Department of Oncology, Derriford Hospital, University Hospitals Plymouth NHS Trust, United Kingdom
 
4
Department of Internal Medicine, Zayed Military Hospital, Abu Dhabi, United Arab Emirates
 
5
Department of Internal Medicine, University Hospitals of Northamptonshire NHS Group, Northampton, United Kingdom
 
6
Department of Intensive Care, Queen Elizabeth Hospital, Gateshead, United Kingdom
 
7
Department of Internal Medicine, Royal Blackburn Hospital, East Lancashire Hospitals NHS Foundation Trust, United Kingdom
 
8
Department of Cardiology, United Lincolnshire Hospitals NHS Trust, United Kingdom
 
9
Department of Gastroenterology, East Lancashire Hospitals NHS Trust, United Kingdom
 
10
Department of Medicine, Sunderland Royal Hospital, South Tyneside and Sunderland NHS Foundation Trust, Sunderland, United Kingdom
 
11
Department of Geriatric Medicine, Basildon and Thurrock University Hospital, United Kingdom
 
12
Department of Cardiology, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom
 
13
Department of Medicine, Dow Medical College, Karachi, Pakistan
 
14
Gabriele Volucke, Department of Medicine, University Hospitals Plymouth NHS Trust, Plymouth, United Kingdom
 
 
Submission date: 2026-07-14
 
 
Acceptance date: 2026-07-26
 
 
Publication date: 2026-09-30
 
 
Corresponding author
Shahzaib Shahzad   

Department of Gastroenterology East Lancashire Hospitals NHS Trust United Kingdom
 
 
Arch Med Sci Atheroscler Dis 2026;11(1):205-230
DOI: https://doi.org/10.5114/amsad/226416
 
 
Article (PDF, 249.87 kB)
Supplementary files
References (64)
 
KEYWORDS
GLP-1 receptor agonists
cardiovascular
diabetes
obesity
meta-analysis
 
TOPICS
ABSTRACT
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may provide cardiovascular benefits beyond glycaemic control. This meta-analysis evaluated their effects on cardiovascular and related clinical outcomes. PubMed, Cochrane Library, and Google Scholar were searched up to March 20, 2026, for randomized controlled trials comparing GLP-1 RAs with placebo in adults with or without type 2 diabetes. Outcomes included mortality, major adverse cardiovascular events (MACE), myocardial infarction, stroke, heart failure hospitalization (HHF), acute kidney injury (AKI), pancreatitis, and infections. Random-effects meta-analyses were conducted using RevMan 5.4.1. Twenty-eight randomized controlled trials (RCTs) involving 52,527 GLP-1 RA recipients and 49,959 placebo recipients were included. GLP-1 RAs were associated with significant reductions in all-cause mortality (RR = 0.86), cardiovascular mortality (RR = 0.86), MACE (RR = 0.87), myocardial infarction (RR = 0.86), stroke (RR = 0.88), and infections (RR = 0.90). No significant effects were observed on AKI, pancreatitis, or HHF. GLP-1 RAs were associated with lower risks of cardiovascular outcomes and mortality.
REFERENCES (64)
1.
Stark BA, DeCleene NK, Desai EC, et al. Global, regional, and national burden of cardiovascular diseases and risk factors in 204 countries and territories, 1990-2023. J Am Coll Cardiol 2025; 86: 2167-243.
Google Scholar
 
 
2.
Wang MS, Deng JW, Geng WY, et al. Temporal trend and attributable risk factors of cardiovascular disease burden for adults 55 years and older in 204 countries/territories from 1990 to 2021: an analysis for the Global Burden of Disease Study 2021. Eur J Prev Cardiol 2025; 32: 539-52.
Google Scholar
 
 
3.
Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019. J Am Coll Cardiol 2020; 76: 2982-3021.
Google Scholar
 
 
4.
Ahmed M, Nofal A, Shafiq A, et al. Rising mortality rates linked to type-2 diabetes and obesity in the United States: an observational analysis from 1999 to 2022. J Diabetes Investig 2025; 16: 492-500.
Google Scholar
 
 
5.
Ahmed M, Javaid H, Shafiq A, et al. Trends and disparities in coronary artery disease and obesity-related mortality in the United States from 1999-2022. Endocrinol Diabetes Metab 2024; 7: e70010.
Google Scholar
 
 
6.
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: 653-62.
Google Scholar
 
 
7.
Hwang T, Franklin J, Kesselheim A. Effect of US Food and Drug Administration’s Cardiovascular Safety Guidance on Diabetes Drug Development. Clin Pharmacol Ther 2017; 102: 290-6.
Google Scholar
 
 
8.
Ahmed M, Burhan M, Shafiq A, et al. GLP-1 and dual GLP-1/GIP receptor agonists in heart failure with mildly reduced or preserved ejection fraction: a systematic review and meta-analysis. Clin Cardiol 2025; 48: e70234.
Google Scholar
 
 
9.
Ahmed M, Hashmi TM, Shahzad M, et al. Cardiovascular and renal outcomes of GLP-1 receptor agonists in type 2 diabetes mellitus: a systematic review and meta-analysis. Eur Heart J Qual Care Clin Outcomes 2026; 12: 980-94.
Google Scholar
 
 
10.
Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375: 311-22.
Google Scholar
 
 
11.
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: 121-30.
Google Scholar
 
 
12.
Shin JI. Second-line glucose-lowering therapy in type 2 diabetes mellitus. Curr Diab Rep 2019; 19: 54.
Google Scholar
 
 
13.
Kristensen SL, Rørth R, Jhund PS, 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 cardiovascular outcome trials. Lancet Diabetes Endocrinol 2019; 7: 776-85.
Google Scholar
 
 
14.
Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019; 393: 31-9.
Google Scholar
 
 
15.
Zelniker TA, Wiviott SD, Raz I, et al. Comparison of the effects of glucagon-like 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: 2022-31.
Google Scholar
 
 
16.
Hosseinpour A, Sood A, Kamalpour J, et al. Glucagon-like peptide-1 receptor agonists and major adverse cardiovascular events in patients with and without diabetes: a meta-analysis of randomized-controlled trials. Clin Cardiol 2024; 47: e24314.
Google Scholar
 
 
17.
Rivera FB, Cruz LLA, Magalong JV, et al. Cardiovascular and renal outcomes of glucagon-like peptide 1 receptor agonists among patients with and without type 2 diabetes mellitus: a meta-analysis of randomized placebo-controlled trials. Am J Prev Cardiol 2024; 18: 100679.
Google Scholar
 
 
18.
Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. PLoS Med 2021; 18: e1003583.
Google Scholar
 
 
19.
Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019: l4898.
Google Scholar
 
 
20.
Cumpston M, Li T, Page MJ, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev 2019; 10: ED000142.
Google Scholar
 
 
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: 2247-57.
Google Scholar
 
 
22.
Margulies KB, Hernandez AF, Redfield MM, et al. Effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction. JAMA 2016; 316: 500.
Google Scholar
 
 
23.
Zhang JY, Wang XY, Wang X. Effects of liraglutide on hemodynamic parameters in patients with heart failure. Oncotarget 2017; 8: 62693-702.
Google Scholar
 
 
24.
Chen WR, Shen XQ, Zhang Y, et al. Effects of liraglutide on left ventricular function in patients with non-ST-segment elevation myocardial infarction. Endocrine 2016; 52: 516-26.
Google Scholar
 
 
25.
Jorsal A, Kistorp C, Holmager P, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (live) – a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail 2017; 19: 69-77.
Google Scholar
 
 
26.
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: 1228-39.
Google Scholar
 
 
27.
Kyhl K, Lønborg J, Vejlstrup N, et al. A post hoc analysis of long-term prognosis after exenatide treatment in patients with ST-segment elevation myocardial infarction. EuroIntervention 2016; 12: 449-55.
Google Scholar
 
 
28.
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: 841-51.
Google Scholar
 
 
29.
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: 1069-84.
Google Scholar
 
 
30.
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: 1394-407.
Google Scholar
 
 
31.
Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375: 1834-44.
Google Scholar
 
 
32.
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023; 389: 2221-32.
Google Scholar
 
 
33.
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.
Google Scholar
 
 
34.
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: 1519-29.
Google Scholar
 
 
35.
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: 109-21.
Google Scholar
 
 
36.
Packer M, Zile MR, Kramer CM, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med 2025; 392: 427-37.
Google Scholar
 
 
37.
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: 2001-12.
Google Scholar
 
 
38.
Bonaca MP, Catarig AM, Houlind K, et al. Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial. Lancet 2025; 405: 1580-93.
Google Scholar
 
 
39.
Davies M, Færch L, Jeppesen OK, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021; 397: 971-84.
Google Scholar
 
 
40.
Zinman B, Aroda VR, Buse JB, et al. Efficacy, safety, and tolerability of oral semaglutide versus placebo added to insulin with or without metformin in patients with type 2 diabetes: the PIONEER 8 Trial. Diabetes Care 2019; 42: 2262-71.
Google Scholar
 
 
41.
Davies MJ, Bergenstal R, Bode B, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes. JAMA 2015; 314: 687.
Google Scholar
 
 
42.
Nauck MA, Stewart MW, Perkins C, et al. Efficacy and safety of once-weekly GLP-1 receptor agonist albiglutide (HARMONY 2): 52 week primary endpoint results from a randomised, placebo-controlled trial in patients with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetologia 2016; 59: 266-74.
Google Scholar
 
 
43.
Reusch J, Stewart MW, Perkins CM, et al. Efficacy and safety of once-weekly glucagon-like peptide 1 receptor agonist albiglutide (HARMONY 1 trial): 52-week primary endpoint results from a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes mellitus not controlled on pioglitazone, with or without metformin. Diabetes Obes Metab 2014; 16: 1257-64.
Google Scholar
 
 
44.
Home PD, Shamanna P, Stewart M, et al. Efficacy and tolerability of albiglutide versus placebo or pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and glimepiride: HARMONY 5. Diabetes Obes Metab 2015; 17: 179-87.
Google Scholar
 
 
45.
Ruff CT, Baron M, Im K, O’Donoghue ML, Fiedorek FT, Sabatine MS. Subcutaneous infusion of exenatide and cardiovascular outcomes in type 2 diabetes: a non-inferiority randomized controlled trial. Nat Med 2022; 28: 89-95.
Google Scholar
 
 
46.
Ahrén B, Johnson SL, Stewart M, et al. HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin. Diabetes Care 2014; 37: 2141-8.
Google Scholar
 
 
47.
Shuja SH, Shuja MH, Shaukat A, et al. GLP-1 receptor agonists and cardiovascular outcomes in adults with diabetes and peripheral artery disease: an updated systematic review and meta-analysis. Am J Cardiol 2026; 258: 268-75.
Google Scholar
 
 
48.
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.
Google Scholar
 
 
49.
Galli M, Benenati S, Simeone B, et al. GLP-1 RAs reduce mortality and cardiovascular events across the spectrum of treated patients: a systematic review and meta-analysis. Eur Heart J 2025; 46 (Suppl 1). doi:10.1093/eurheartj/ehaf784.4322.
CrossRef
 
Google Scholar
 
 
50.
Sun F, Wu S, Wang J, et al. Effect of glucagon-like peptide-1 receptor agonists on lipid profiles among type 2 diabetes: a systematic review and network meta-analysis. Clin Ther 2015; 37: 225-41.e8.
Google Scholar
 
 
51.
Rizzo M, Chandalia M, Patti AM, et al. Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study. Cardiovasc Diabetol 2014; 13: 49.
Google Scholar
 
 
52.
Gaspari T, Welungoda I, Widdop RE, Simpson RW, Dear AE. The GLP-1 receptor agonist liraglutide inhibits progression of vascular disease via effects on atherogenesis, plaque stability and endothelial function in an ApoE −/− mouse model. Diab Vasc Dis Res 2013; 10: 353-60.
Google Scholar
 
 
53.
Irace C, De Luca S, Shehaj E, et al. Exenatide improves endothelial function assessed by flow mediated dilation technique in subjects with type 2 diabetes: results from an observational research. Diab Vasc Dis Res 2013; 10: 72-7.
Google Scholar
 
 
54.
Salcedo I, Tweedie D, Li Y, Greig NH. Neuroprotective and neurotrophic actions of glucagon-like peptide-1: an emerging opportunity to treat neurodegenerative and cerebrovascular disorders. Br J Pharmacol 2012; 166: 1586-99.
Google Scholar
 
 
55.
Michaelsen MK, Drasbek KR, Valentin JB, et al. GLP-1 receptor agonists as treatment of nondiabetic ischemic stroke: a systematic review and meta-analysis. Stroke 2026; 57: 415-37.
Google Scholar
 
 
56.
Zhu Q, Luo Y, Wen Y, Wang D, Li J, Fan Z. Semaglutide inhibits ischemia/reperfusion-induced cardiomyocyte apoptosis through activating PKG/PKC/ERK1/2 pathway. Biochem Biophys Res Commun 2023; 647: 1-8.
Google Scholar
 
 
57.
Villaschi A, Ferrante G, Cannata F, et al. GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis. Clin Res Cardiol 2024; 113: 898-909.
Google Scholar
 
 
58.
Waqas SA, Sohail MU, Saad M, et al. Efficacy of GLP-1 receptor agonists in patients with heart failure and mildly reduced or preserved ejection fraction: a systematic review and meta-analysis. J Card Fail 2025; 31: 1076-80.
Google Scholar
 
 
59.
Baggio LL, Ussher JR, McLean BA, et al. The autonomic nervous system and cardiac GLP-1 receptors control heart rate in mice. Mol Metab 2017; 6: 1339-49.
Google Scholar
 
 
60.
Skov J, Dejgaard A, Frøkiær J, et al. Glucagon-like peptide-1 (GLP-1): effect on kidney hemodynamics and renin-angiotensin-aldosterone system in healthy men. J Clin Endocrinol Metab 2013; 98: E664-71.
Google Scholar
 
 
61.
Martins FL, Bailey MA, Girardi ACC. Endogenous activation of glucagon-like peptide-1 receptor contributes to blood pressure control. Hypertension 2020; 76: 839-48.
Google Scholar
 
 
62.
Ahmed M, Zulfiqar E, Shafiq A, et al. Type 2 diabetes mellitus–related mortality in the United States, 1999 to 2023. JACC Adv 2025; 4: 101882.
Google Scholar
 
 
63.
Han S, Liu Y, Xing B, et al. Association of glucagon-like peptide-1 receptor agonist use with risk of infections: a systematic review and meta-analysis. J Infect 2025; 91: 106645.
Google Scholar
 
 
64.
Ayoub M, Chela H, Amin N, et al. Pancreatitis risk associated with GLP-1 receptor agonists, considered as a single class, in a comorbidity-free subgroup of type 2 diabetes patients in the United States: a propensity score-matched analysis. J Clin Med 2025; 14: 944.
Google Scholar
 
 
Share
Send by email
RELATED ARTICLE
Cerebral embolic protection in patients undergoing transcatheter aortic valve implantation: an updated meta-analysis of randomised controlled trials
Colchicine’s promise in post-ablation atrial fibrillation: a meta-analysis
Trends in mortality from acute myocardial infarction among the obese population in the United States from 1999 to 2020: insights from CDC WONDER
Cortisol as a factor contributing to the development of non-alcoholic fatty liver disease in severely obese patients: a single-center prospective study
Efficacy and safety of myosin inhibitors for symptomatic hypertrophic cardiomyopathy: systematic review and meta-analysis
Indexes
 
Keywords index
Topics index
Authors index
eISSN:2451-0629
Journals System - logo
© 2006-2026 Journal hosting platform by Bentus
Scroll to top