Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Outcomes across the Spectrum of Kidney Disease: A Systematic Review and Meta-Analysis.

KEY POINTS

The effect of sodium-glucose cotransporter 2 inhibitors in preventing kidney outcomes in populations at lower risk of kidney disease remains uncertain. Pooled data from randomized controlled trials show that sodium-glucose cotransporter 2 inhibitors prevent kidney outcomes across the spectrum of kidney disease risk.

BACKGROUND

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown to reduce clinically meaningful kidney outcomes in individuals with CKD at high risk of adverse outcomes. The effect of these agents in preventing clinically meaningful kidney outcomes in populations at lower risk remains uncertain. We aim to evaluate the effect of SGLT2 inhibitors on kidney outcomes across the Kidney Disease Improving Global Outcomes (KDIGO) classification and urinary albumin-creatinine ratio (UACR) levels.

METHODS

We have searched medical literature analysis and retrieval system online (PubMed), excerpta medica database, and Cochrane Central Register of Controlled Trials from inception up to August 8, 2023. In pairs, researchers selected large (≥500 participants per arm) randomized placebo-controlled trials of SGLT2 inhibitors, with a minimum duration of 1 year. Researchers independently extracted study-level data and assessed within-study risk of bias with the risk of bias 2.0 tool and quality of evidence with grading of recommendations, assessment, development and evaluation.

RESULTS

We included ten trials, encompassing 78,184 participants and a median follow-up of 2.7 years. Risk of bias was overall low. We performed meta-analyses summarizing individual study hazard ratios (HRs) and 95% confidence intervals (CIs) using a random-effects model. SGLT2 inhibitors reduced the composite kidney outcome across all KDIGO (HR [95% CI]: low 0.48 [0.32 to 0.71], moderate 0.60 [0.39 to 0.93], high 0.59 [0.47 to 0.74], very high 0.59 [0.49 to 0.72]) and UACR (HR [95% CI]: <30 mg/g 0.62 [0.50 to 0.78], ≥30 to ≤300 mg/g 0.80 [0.67 to 0.96], >300 mg/g 0.61 [0.52 to 0.73]) groups, without evidence of heterogeneity between groups. A small proportion of participants without diabetes in low-risk groups were referred, and there was lack of standardization of composite outcomes.

CONCLUSIONS

SGLT2 inhibitors consistently reduce kidney outcomes across the spectrum of KDIGO classes and UACR levels.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER

: CRD42023492877.