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Meta-Analysis
. 2026 Jan 1;110(1):e217-e228.
doi: 10.1097/TP.0000000000005496. Epub 2025 Jul 24.

SGLT2 Inhibitors and GLP-1 Receptor Agonists in Kidney Transplantation: A Systematic Review and Meta-Analysis

Sul A Lee  1   2 , Rucháma Verhoeff  2 , Frank Hullekes  2 , Panupong Hansrivijit  3   4 , Ron W F de Bruin  5 , Robert J Porte  5 , Leonardo V Riella  1   2   6
Affiliations
Meta-Analysis

SGLT2 Inhibitors and GLP-1 Receptor Agonists in Kidney Transplantation: A Systematic Review and Meta-Analysis

Sul A Lee et al. Transplantation. .

Abstract

Background: Kidney transplant (KT) recipients experience high rates of cardiovascular disease, allograft dysfunction, and diabetes, negatively impacting long-term outcomes. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide cardiovascular and kidney benefits in non-KT recipients, but evidence in KT recipients remains limited. This systematic review and meta-analysis provide updated evidence on the efficacy and safety of SGLT2i and GLP-1RAs on KT recipients.

Methods: A comprehensive search of MEDLINE, Embase, and Cochrane databases was conducted through February 27, 2025. Data extraction, risk of bias assessment, and meta-analysis were performed using standardized methods with a random-effects model.

Results: A total of 32 studies, including 7834 KT recipients, were analyzed, comprising 21 studies (3856 patients) on SGLT2i and 12 studies (3978 patients) on GLP-1RAs. Their use was associated with reduced mortality and improved cardiovascular and kidney outcomes in matched control studies. Both agents promoted weight loss (SGLT2i: standardized mean difference -0.59; 95% confidence interval [CI], -1.04 to -0.15; GLP-1RA: standardized mean difference -0.27; 95% CI, -0.44 to -0.10) and hemoglobin A1c reduction (SGLT2i: mean difference, -0.33%; 95% CI, -0.55% to -0.12%; GLP-1RA: mean difference, -0.48%; 95% CI, -0.82% to -0.13%) while maintaining stable kidney function. SGLT2i increased serum magnesium levels and reduced uric acid levels. Safety analysis showed no increased risk of infections (SGLT2i) or pancreatitis (GLP-1RAs).

Conclusions: SGLT2i and GLP-1RA were associated with improved survival, cardiovascular, and kidney outcomes with a favorable safety profile. Future randomized controlled trials are necessary to confirm the efficacy and safety in this high-risk population.

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Conflict of interest statement

This study was funded, in part, by a U2C/TL1 Harvard Kidney, Urology, and Hematology Training Institute Network grant (TL1DK143273) awarded to S.A.L. and by a National Institutes of Health grant (R01AI-143887) to L.V.R.. L.V.R. has served on an advisory board for Novo Nordisk; however, this relationship did not influence the design, conduct, analysis, or reporting of this study. The other authors declare no conflicts of interest.

References

    1. Abecassis M, Bartlett ST, Collins AJ, et al. Kidney transplantation as primary therapy for end-stage renal disease: a National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQITM) conference. Clin J Am Soc Nephrol. 2008;3:471–480.
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    1. Patel SM, Kang YM, Im K, et al. Sodium-glucose cotransporter-2 inhibitors and major adverse cardiovascular outcomes: a SMART-C collaborative meta-analysis. Circulation. 2024;149:1789–1801.
    1. Baigent C, Emberson J, Hayne R, et al. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022;400:1788–1801.
    1. Wiviott SD, Raz I, Bonaca MP, et al.; DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347–357.

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