A systematic review and meta-analysis assessing the safety and efficacy of sodium-glucose co-transporter 2 inhibitor use in hospitalized patients

Background Safety and efficacy of sodium–glucose co-transporter 2 (SGLT2) inhibitors in hospitalized patients is unclear. Purpose To evaluate outcomes of inpatient SGLT2 inhibitor use. Data sources MEDLINE, Embase, Emcare and Cochrane databases were searched until 29th May 2024. Study selection Randomized controlled trials (RCTs) and observational cohort studies assessing 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 using the I2 statistic. Twenty-three RCTs comprising 19,846 participants (29.5% with type 2 diabetes) comparing SGLT2 inhibitors to placebo or active comparator were included. Ketoacidosis rates were 0.210 (95% CI 0.119 to 0.370) per 100 person-years with SGLT2 inhibitors and 0.140 (95% CI 0.070 to 0.280) per 100 person-years with control (rate ratio 1.50, 95% CI 0.56 to 4.23, p=0.38). SGLT2 inhibitor use was associated with lower readmission and urgent visits (odds ratio [OR] 0.64, 95% CI 0.47 to 0.86, p<0.01) and mortality (OR 0.74, 95% CI 0.56 to 0.98, p=0.03) in heart failure trials, and lower acute kidney injury (OR 0.76, 95% CI 0.60 to 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.