The Efficacy and Safety of SGLT2 Inhibitors in Diabetes Kidney Transplant Recipients: A Systematic Review and Meta-Analysis.
Boonpiraks, K., et al.F1000Res. 2025 Mar 25;14:329.
Aims
To evaluate the efficacy and safety of SGLT-2 inhibitors in kidney transplant recipients with diabetes (pre-existing T2DM and PTDM).
Interventions
The intervention across the studies were the SGLT-2 inhibitors (most commonly empagliflozin, canagliflozin and dapagliflozin). The control groups varied by study, placebo in one RCT, and in other studies other glucose-lowering therapies (insulin, metformin, DPP-4 inhibitors, sulfonylureas).
Participants
Systematic review/meta-analysis of 7 studies (5 retrospective cohorts, 2 RCTs) with 2713 total patients, including 545 patients treated with SGLT-2 inhibitors. Diabetes within the studies was predominantly T2DM (74%) vs PTDM (26%).
Outcomes
The renal endpoints were eGFR and Proteinuria (UPCR). The metabolic outcomes were HbA1c, BMI and SBP. The clinical outcomes were all-cause mortality and cardiovascular disease.
Follow-up
Median follow-up across included studies was 9 months.
CET Conclusions
This meta-analysis suggests that in diabetic kidney recipients, SGLT-2 inhibitors improve glycaemic control (modest reduction, WMD about −0.37%; high heterogeneity I² ~93%) and reduce BMI (WMD about −0.89 kg/m²) without a detected increase in infections or rejection but show no clear short-term benefit on eGFR (WMD ~0.69 mL/min/1.73m²; heterogeneity I² ~55%) or proteinuria. All-cause mortality showed a signal for slight reduction (RR ~0.25) but based on few events (40 deaths) and only in 3 studies with a cardiovascular disease reduction signal (RR ~0.41), but again only based on 3 studies. Overall, the quality of evidence would be considered low-to-moderate for most endpoints because the evidence base is dominated by retrospective cohorts with heterogeneous comparators, short follow-up, and substantial heterogeneity for key metabolic outcomes. Mortality and cardiovascular findings are interesting but are based on small numbers of events and limited studies, so there is quite possibly residual confounding and/or selection bias. The clinical impact is not significant, given that only 58 of the 2713 patients in the analysis are from RCTs. It presents a use case for SGLT-2 inhibitors in diabetic kidney recipients in which weight, glycaemia, and cardiovascular risk are of particular concern, but it does not support claims for the renal-protection effects of SGLT-2 inhibitors, this would require without larger and longer randomised studies, which would be challenging given the likely modest effect size.
Trial registration
PROSPERO: CRD42023404886