Cited by 29Diabetes Treatment and ManagementChronic Kidney Disease and DiabetesHeart Failure Treatment and Management

Effects of GLP‐1 receptor agonists on cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease: A systematic review and meta‐analysis

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Kelly, Michael, Lewis, Jelena, Rao, Hindu, Carter, Jessica, Portillo, Ivan, Beuttler, Richard·2022·Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy

Abstract

Aim: To evaluate the cardiovascular outcomes of glucagon‐like peptide‐1 receptor agonists (GLP1‐RA) in patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD). Materials and Methods: We searched PubMed, Ovid MEDLINE, CINAHL, and Web of Science databases for randomized controlled trials reporting event rates for a composite cardiovascular outcome of cardiovascular death, myocardial infarction, and stroke in patients with T2DM and CKD receiving GLP1‐RA or placebo. Studies were restricted to those reporting specific event rates for patients with CKD separately from the overall population. We conducted a meta‐analysis using a random‐effects model. This meta‐analysis was registered on PROSPERO (CRD42022320157). Results: A total of four studies comprising 7130 patients was included in our analysis. Four different GLP1‐RA were assessed in a population with CKD defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m 2. Treatment with GLP1‐RA was not associated with a significant reduction in the composite cardiovascular end point of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (odds ratio (OR) 0.80; 95% confidence interval (CI), 0.59–1.07; p = 0.13) among patients with T2DM and CKD. Individual components of the composite cardiovascular end point were assessed in two trials and did not show evidence of an effect of GLP1‐RA in reducing cardiovascular end points. Conclusions: Pooled analysis of clinical trials reporting separate cardiovascular events rates in patients with T2DM and CKD did not find GLP1‐RA to be associated with a reduction in composite cardiovascular event rates. Select GLP1‐RA may offer cardiovascular event reduction in patients with T2DM and CKD, but this does not appear to be a class effect. Use of GLP1‐RA with demonstrated cardiovascular benefits should be preferred in patients with CKD and T2DM to further reduce cardiovascular risk.

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  • GLP-1 RAs reduce risks of cardiovascular disease events and slow progression of CKD.

    “GLP-1 RAs are suggested for cardiovascular risk reduction if such risk is a predominant problem, as they reduce risks of CVD events and slow progression of CKD (109,118-122).”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [122]

    The Conclusion says select GLP-1 receptor agonists have reduced cardiovascular event rates, but this meta-analysis found no significant reduction in the composite cardiovascular endpoint for patients with type 2 diabetes and CKD; it does not establish a class-wide effect. The Introduction mentions renoprotection and recommends agents with demonstrated renal benefit, but the paper does not establish that GLP-1 receptor agonists slow CKD progression. (LLM, conf=0.88)

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Research works printed but not linked: 16

  1. [1]Sarnak MJ, Amann K, Bangalore S, et al. The present and future chronic kidney disease and coronary artery disease JACC state‐of‐the‐art review. J Am Coll Cardiol. 2019; 74(14): 1823‐ 1838. doi: 10.1016/j.jacc.2019.08.1017 31582143 · DOI
  2. [2]Jankowski J, Floege J, Fliser D, Böhm M, Marx N. Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options. Circulation. 2021; 143(11): 1157‐ 1172. doi: 10.1161/CIRCULATIONAHA.120.050686 33720773 PMC7969169 · DOI
  3. [3]Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007‐2017. Cardiovasc Diabetol. 2018; 17(1): 83. doi: 10.1186/s12933-018-0728-6 29884191 PMC5994068 · DOI · Paper page
  4. [4]Lovre D, Shah S, Sihota A, Fonseca VA. Managing diabetes and cardiovascular risk in chronic kidney disease patients. Endocrinol Metab Clin N Am. 2018; 47(1): 237‐ 257. doi: 10.1016/j.ecl.2017.10.006 PMC5806139 29407054 · DOI
  5. [5]Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes Management in Chronic Kidney Disease. Kidney Int. 2020; 98(4 S): S1‐ S115. doi: 10.1016/j.kint.2020.06.019 32998798 · DOI · Paper page
  6. [6]Brown JM, Everett BM. Cardioprotective diabetes drugs: what cardiologists need to know. Cardiovasc Endocrinol Metab. 2019; 8(4): 96‐ 105. doi: 10.1097/XCE.0000000000000181 31942550 PMC6946151 · DOI
  7. [7]Cox EJ, Alicic RZ, Neumiller JJ, Tuttle KR. Clinical evidence and proposed mechanisms for cardiovascular and kidney benefits from glucagon‐like Peptide‐1 receptor agonists. US Endocrinol. 2020; 16(2): 80‐ 87. doi: 10.17925/USE.2020.16.2.80 · DOI
  8. [8]American Diabetes Association. Pharmacologic approaches to glycemic treatment: standards of medical Care in Diabetes—2022. Diabetes Care. 2021; 45(Suppl_1): S125‐ S143. doi: 10.2337/dc22-S009 34964831 · DOI · Paper page
  9. [14]Bethel MA, Mentz RJ, Merrill P, et al. Microvascular and cardiovascular outcomes according to renal function in patients treated with once‐weekly exenatide: insights from the EXSCEL trial. Diabetes Care. 2020; 43(2): 446‐ 452. doi: 10.2337/dc19-1065 31757838 PMC7411285 · DOI · Paper page
  10. [15]Mann JFE, Fonseca V, Mosenzon O, et al. Effects of liraglutide versus placebo on cardiovascular events in patients with type 2 diabetes mellitus and chronic kidney disease. Circulation. 2018; 138(25): 2908‐ 2918. doi: 10.1161/CIRCULATIONAHA.118.036418 30566006 PMC6296845 · DOI · Paper page
  11. [16]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(9): 841‐ 851. doi: 10.1056/NEJMoa1901118 31185157 · DOI · Paper page
  12. [19]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(13): 1228‐ 1239. doi: 10.1056/NEJMoa1612917 28910237 PMC9792409 · DOI · Paper page
  13. [20]Tuttle KR, Heilmann C, Hoogwerf BJ, Brown C, Anderson PW. Effects of exenatide on kidney function, adverse events, and clinical end points of kidney disease in type 2 diabetes. Am J Kidney Dis off J Natl Kidney Found. 2013; 62(2): 396‐ 398. doi: 10.1053/j.ajkd.2013.03.026 23684754 · DOI
  14. [25]American Diabetes Association. Chronic kidney disease and risk management: standards of medical Care in Diabetes—2022. Diabetes Care. 2021; 45(Supplement_1): S175‐ S184. doi: 10.2337/dc22-S011 34964873 · DOI · Paper page
  15. [26]Qiu R, Balis D, Xie J, Davies MJ, Desai M, Meininger G. Longer‐term safety and tolerability of canagliflozin in patients with type 2 diabetes: a pooled analysis. Curr Med Res Opin. 2017; 33(3): 553‐ 562. doi: 10.1080/03007995.2016.1271780 27977934 · DOI
  16. [27]Qiu H, Novikov A, Vallon V. Ketosis and diabetic ketoacidosis in response to SGLT2 inhibitors: basic mechanisms and therapeutic perspectives. Diabetes Metab Res Rev. 2017; 33(5): e2886. doi: 10.1002/dmrr.2886 28099783 · DOI

Cited by

Sorted by citations

Authors
Kelly, M., Lewis, J., Rao, H., Carter, J., Portillo, I., & Beuttler, R.
Affiliations
  • Thomas Jefferson University (US)
  • Chapman University (US)
Corresponding author
Rao, Hindu
Venue
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy
Publisher
Wiley
Published
2022-11-04
Volume
42
Issue
12
Pages
921-928
ISSN
  • 0277-0008 (ISSN-L)
  • 1875-9114
OpenAlex
W4307093785
Cited by
29
References
8
Citations by year
2026: 3 · 2025: 11 · 2024: 10 · 2023: 4 · 2022: 1
FWCI
0.93
Type
journal article
Language
en
Open access
Locations
  • Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Chapman University Digital Commons (Chapman University) (submittedVersion, cc-by-nc)
  • The Medicine Forum (submittedVersion, cc-by-nc)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
Keywords
GLP-1 receptor agonists, type 2 diabetes, chronic kidney disease, cardiovascular outcomes, cardiovascular mortality, myocardial infarction, stroke, cardiovascular risk reduction
MeSH terms
Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus, Type 2, Humans, Myocardial Infarction, Stroke, Renal Insufficiency, Chronic

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