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

Abstract

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.