A Systematic Review and Meta-analysis on the Safety and Efficacy of Sodium–Glucose Cotransporter 2 Inhibitor Use in Hospitalized Patients

BACKGROUND The safety and efficacy of sodium–glucose cotransporter 2 (SGLT2) inhibitors in hospitalized patients are unclear. PURPOSE To evaluate outcomes of inpatient SGLT2 inhibitor use. DATA SOURCES MEDLINE, Embase, Emcare, and Cochrane databases were searched through 29 May 2024. STUDY SELECTION Randomized controlled trials (RCTs) and observational cohort studies with assessment of SGLT2 inhibitor use in patients hospitalized for any reason were included. DATA EXTRACTION Study characteristics and clinical outcomes were extracted. DATA SYNTHESIS We performed a random-effects meta-analysis analyzing RCTs and cohort studies separately. Heterogeneity was quantified with the I2 statistic. Twenty-three RCTs comprising 19,846 participants (29.5% with type 2 diabetes) with comparison of SGLT2 inhibitors with placebo or active comparator were included. Ketoacidosis rates were 0.210 per 100 person-years (95% CI 0.119, 0.370) for SGLT2 inhibitors and 0.140 per 100 person-years (95% CI 0.070, 0.280) for control (rate ratio 1.50 [95 CI 0.56, 4.23], P = 0.38). SGLT2 inhibitor use was associated with fewer readmissions and urgent visits (odds ratio [OR] 0.64 [95 CI 0.47, 0.86], P < 0.01) and lower mortality rates (OR 0.74 [95% CI 0.56, 0.98], P = 0.03) in heart failure trials and lower incidence of acute kidney injury (OR 0.76 [95% CI 0.60, 0.97], P = 0.03) among all RCTs. Twenty observational studies were included and did not show increased adverse events. LIMITATIONS Ketoacidosis rates were low, likely leading to lack of power to detect significant differences. CONCLUSIONS SGLT2 inhibitor use among hospitalized patients was associated with numerically higher rates of ketoacidosis, although further studies are required.