SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials.

AIMS

There is concern about the infection-related safety profile of sodium-glucose co-transporter 2 (SGLT-2) inhibitors. We aimed to determine the effect of SGLT-2 inhibitors on genitourinary and other infections via systematic review and meta-analysis of randomized controlled trials (RCTs).

METHODS

We conducted a systematic search of Medline, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov to identify double-blinded RCTs enrolling ≥ 50 patients with type 2 diabetes which compared an SGLT-2 inhibitor to placebo or active comparator. Two independent reviewers extracted data and appraised study quality. Data were pooled using random-effects models.

RESULTS

Eighty-six RCTs enrolling 50,880 patients were included. SGLT-2 inhibitors increased the risk of genital infections compared to placebo (relative risk [RR] 3.37, 95% CI 2.89-3.93, I 0%) and active comparator (RR 3.89, 95% CI 3.14-4.82, I 0.3%). The risk of urinary tract infection (UTI) was not increased with SGLT-2 inhibitors compared to placebo (RR 1.03, 95% CI 0.96-1.11, I 0%) or active comparator (RR 1.08, 95% CI 0.93-1.25, I 22%). In drug-specific analyses, only dapagliflozin 10 mg daily was associated with a significantly increased risk of UTI compared to placebo (RR 1.33, 95% CI 1.10-1.61, I 0%). SGLT-2 inhibitors were associated with a reduced risk of gastroenteritis (RR 0.38, 95% CI 0.20-0.72, I 0%) but did not affect the risk of respiratory tract infections.

CONCLUSIONS/INTERPRETATION: SGLT-2 inhibitors are associated with an increased risk of genital tract infections. Although there is no association overall between SGLT-2 inhibitors and UTI, higher doses of dapagliflozin are associated with an increased risk.