The safety outcomes of sodium-glucose cotransporter 2 inhibitors in patients with different renal function: A systematic review and meta-analysis.

Abstract

AIMS\nWe aimed to assess whether the safety outcomes exerted by sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with different renal function at baseline.\n\n\nDATA SYNTHESIS\nWe searched randomized controlled trials comparing SGLT2 inhibitors with placebo in participants simultaneously involving the entire range of estimated glomerular filtration rate (eGFR) levels at baseline in one study. According to eGFR, we divided the population into two subgroups with eGFR <60\xa0ml/min/1.73\xa0m2 and eGFR≥60\xa0ml/min/1.73\xa0m2. Data from the CANVAS program, CREDENCE, EMPA-REG OUTCOME, DECLARE-TIMI 58, DAPA-HF, and EMPA-REG RENAL were included. SGLT2 inhibitors significantly reduced the risk of all serious adverse events (HR 0.91 [95% CI 0.87 to 0.95], p\xa0<\xa00.001) and acute kidney injury (HR 0.74 [95% CI 0.64 to 0.85], p\xa0<\xa00.001). Except for high risk of genital infection, SGLT2 inhibitors did not increase the risk of amputation, fracture, hyperkalemia, hypoglycemia, volume depletion, or urinary tract infection. Further analyses showed that these safety outcomes were similar between subgroups (p-interaction\xa0>\xa00.05). For osmotic diuresis, SGLT2 inhibitors significantly increased the risk by 75% (p\xa0=\xa00.036), and subgroup analyses showed that this effect was completely attributed to the increase in patients with eGFR ≥60\xa0ml/min/1.73\xa0m2 (p-interaction<0.001).\n\n\nCONCLUSION\nThe indication of no risk of osmotic diuresis in patients with eGFR<60\xa0ml/min/1.73\xa0m2 and the consistency of other safety outcomes across different baseline renal function may allow additional individuals to safely use SGLT2 inhibitors.