SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials

Rationale & Objective There are few data on the absolute effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors, despite their importance in treatment decision making. We investigated absolute treatment effects according to baseline kidney disease status. Study Design Meta-analysis. Study Populations Adults with type 2 diabetes, chronic kidney disease, or heart failure. Selection Criteria for Studies Randomized controlled trials of SGLT2 inhibitors (10 trials to November 20, 2020) for clinical outcomes of kidney disease progression, heart failure events, and major cardiovascular events. Data Extraction Publications of 10 trials to November 20, 2020. Analytical Approach The incidence rate difference (IRD) between SGLT2 inhibitor and placebo was compared across estimated glomerular filtration rate (eGFR) or urinary albumin-creatinine ratio (UACR) subgroups. Results Subgroup analyses included data from seven trials (61,821 participants with diabetes or chronic kidney disease). SGLT2 inhibitor treatment, in eGFR subgroups of  300, 30 to 300, and  Limitations Study-level data rather than individual patient data were used. Conclusions SGLT2 inhibitor treatment resulted in greater reductions of cardiovascular events in patients with lower eGFR and higher albuminuria and had substantially greater absolute benefits of renoprotection in patients with overt albuminuria than in their counterparts.