Cardiorenal Effects of SGLT2 Inhibitors: A Meta-Analysis of Randomized Controlled Trials
Abstract
Type 2 diabetes (T2D) and hypertension are major causes of end-stage renal disease (ESRD) and cardiovascular complications. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, also known as gliflozins, initially developed as antidiabetic agents, have demonstrated significant cardiorenal protective effects independent of glycemic control. This meta-analysis aimed to evaluate their impact on the prevention of ESRD and major adverse cardiovascular events (MACE). A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched from 2008 to 2025. Randomized controlled trials comparing SGLT2 inhibitors with placebo were included. The primary outcomes were a composite renal endpoint (progression to ESRD, ≥50% decline in glomerular filtration rate, initiation of renal replacement therapy, or renal death) and MACE (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Statistical analyses were performed using RevMan 5.4, applying fixed- or random-effects models depending on heterogeneity (I²). Results were expressed as odds ratios (OR) with 95% confidence intervals (95% CI). A total of 13 randomized controlled trials including 90,413 participants were analyzed. SGLT2 inhibitors significantly reduced the risk of major renal events (OR = 0.68; 95% CI: 0.59–0.77; I² = 61%), major cardiovascular events (OR = 0.88; 95% CI: 0.83–0.93; I² = 44%), and all-cause mortality (OR = 0.89; 95% CI: 0.85–0.93). In conclusion, SGLT2 inhibitors confirm their major cardiorenal benefits, independent of glycemic control, significantly reducing progression to ESRD, major cardiovascular events, and overall mortality. These findings support their early use in patients at high cardiorenal risk, in line with recent international recommendations.
Keywords : SGLT2 inhibitors; Gliflozins; End-stage renal disease; Type 2 diabetes; Hypertension; Cardiovascular outcomes; Meta-analysis; PRISMA
Keywords:
SGLT2 inhibitors, Gliflozins, End-stage renal disease, Type 2 diabetes, Hypertension, Cardiovascular outcomes, Meta-analysis, PRISMADOI
https://doi.org/10.22270/jddt.v16i5.7782References
1. ANSD/MSAS. National Survey on Risk Factors for Non-Communicable Diseases. Ministry of Health and Social Action, Senegal; 2016. Available from: https://www.ansd.sn/
2. Scheen AJ, Paquot N. Type 2 diabetes: insight into a complex disease. Rev Med Liège. 2012;67(1):326-331.
3. Le Neindre CL. Atlas of End-Stage Renal Disease in France.
4. African Health Observatory Platform. Addressing the increase of kidney diseases in Senegal. Available from: https://medium.com/ (Accessed October 15, 2025).
5. Lv JC, Zhang LX. Prevalence and disease burden of chronic kidney disease. In: Liu BC, Lan HY, Lv LL, editors. Renal Fibrosis: Mechanisms and Therapies. Singapore: Springer; 2019. p. 3-15. https://doi.org/10.1007/978-981-13-8871-2_1 PMid:31399958
6. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Prevention of chronic kidney disease. Available from: https://www.niddk.nih.gov/ (Accessed March 9, 2025).
7. Hamdini L, et al. Use of SGLT2 inhibitors in chronic kidney disease. Presse Med Form. 2023;4(2):129-134. https://doi.org/10.1016/j.lpmfor.2023.04.014
8. Evans M, et al. Defining the role of SGLT2 inhibitors in primary care: time to think differently. Diabetes Ther. 2022;13(5):889-911. https://doi.org/10.1007/s13300-022-01242-y PMid:35349120 PMCid:PMC9076801
9. CISMeF. HeTOP terminology portal. Available from: https://www.hetop.eu/hetop/ (Accessed October 12, 2025).
10. Guyatt G, et al. GRADE guidelines: introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383-394. https://doi.org/10.1016/j.jclinepi.2010.04.026 PMid:21195583
11. Haddaway NR, Page MJ, Pritchard CC, McGuinness LA. PRISMA 2020: an R package for producing compliant flow diagrams. Campbell Syst Rev. 2022;18(2):e1230. https://doi.org/10.1002/cl2.1230 PMid:36911350 PMCid:PMC8958186
12. Neal B, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-657. https://doi.org/10.1056/NEJMoa1611925 PMid:28605608
13. Figtree GA, et al. Effects of canagliflozin on heart failure outcomes in type 2 diabetes. Circulation. 2019;139(22):2591-2593. https://doi.org/10.1161/CIRCULATIONAHA.119.040057 PMid:30882240
14. Wiviott SD, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357. https://doi.org/10.1056/NEJMoa1812389 PMid:30415602
15. Zinman B, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128. https://doi.org/10.1056/NEJMoa1504720 PMid:26378978
16. Wanner C. EMPA-REG OUTCOME: the nephrologist's perspective. Am J Cardiol. 2017;120(1):S59-S67. https://doi.org/10.1016/j.amjcard.2017.05.012 PMid:28606346
17. Cannon CP, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med. 2020;383(15):1425-1435. https://doi.org/10.1056/NEJMoa2004967 PMid:32966714
18. McMurray JJV, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995-2008. https://doi.org/10.1056/NEJMoa1911303 PMid:31535829
19. McCausland FR, et al. Dapagliflozin and kidney outcomes in heart failure. JAMA Cardiol. 2023;8(1):56. https://doi.org/10.1001/jamacardio.2022.4210 PMid:36326604 PMCid:PMC9634592
20. Solomon SD, et al. Dapagliflozin in heart failure with preserved or mildly reduced ejection fraction. N Engl J Med. 2022;387(12):1089-1098. https://doi.org/10.1056/NEJMoa2206286 PMid:36027570 PMCid:PMC10327875
21. Anker SD, et al. Empagliflozin in heart failure with preserved ejection fraction. N Engl J Med. 2021;385(16):1451-1461. https://doi.org/10.1056/NEJMoa2107038 PMid:34449189
22. Packer M, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413-1424. https://doi.org/10.1056/NEJMoa2022190 PMid:32865377
23. Bhatt DL, et al. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021;384(2):117-128. https://doi.org/10.1056/NEJMoa2030183 PMid:33200892 PMCid:PMC9668858
24. Perkovic V, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-2306. https://doi.org/10.1056/NEJMoa1811744 PMid:30990260
25. Heerspink HJL, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436-1446. https://doi.org/10.1056/NEJMoa2024816 PMid:32970396
26. Herrington WG, et al. Empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117-127. https://doi.org/10.1056/NEJMoa2204233 PMid:36331190 PMCid:PMC7614055
27. Sridhar VS, et al. Sotagliflozin and kidney outcomes in CKD. Clin J Am Soc Nephrol. 2024;19(5):557-564. https://doi.org/10.2215/CJN.0000000000000414 PMid:38277468 PMCid:PMC11108248
28. Bhatt DL, et al. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. 2021;384(2):129-139. https://doi.org/10.1056/NEJMoa2030186 PMid:33200891 PMCid:PMC9668858
29. Baigent C, Emberson J. Impact of diabetes on SGLT2 inhibitors and kidney outcomes: collaborative meta-analysis. Lancet. 2022;400(10365):1788-1801. https://doi.org/10.1016/S0140-6736(22)02074-8 PMid:36351458
30. Dharia A, et al. SGLT2 inhibitors: the sweet success for kidneys. Annu Rev Med. 2023;74:369-384. https://doi.org/10.1146/annurev-med-042921-102135 PMid:36706745
31. Fall M, et al. Drug interactions in cardiovascular prevention: a meta-analysis. Therapies. 2022;77(6):663-672. https://doi.org/10.1016/j.therap.2022.04.004 PMid:35643744
32. Rossing P, et al. KDIGO 2022 clinical practice guideline for diabetes management in CKD. Kidney Int. 2022;102(5):S1-S127. https://doi.org/10.1016/j.kint.2022.06.008 PMid:36272764
33. American Diabetes Association. Pharmacologic approaches to glycemic treatment. Diabetes Care. 2017;40(Suppl 1):S64-S74. https://doi.org/10.2337/dc17-S011 PMid:27979895
34. Heerspink HJL, et al. Kidney-related adverse events in the CREDENCE trial. Am J Kidney Dis. 2022;79(2):244-256.e1. https://doi.org/10.1053/j.ajkd.2021.05.005 PMid:34029680
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