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

Robert Puckrin,Marie-Philippe Saltiel,Oriana H Y Yu,Kristian B Filion,Laurent Azoulay,Pauline Reynier

doi:10.1007/s00592-018-1116-0

Robert Puckrin, Marie-Philippe Saltiel + Show 4 more

Open Access

https://doi.org/10.1007/s00592-018-1116-0

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Abstract

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). 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. 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, I2 0%) and active comparator (RR 3.89, 95% CI 3.14-4.82, I2 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, I2 0%) or active comparator (RR 1.08, 95% CI 0.93-1.25, I2 22%). In drug-specific analyses, only dapagliflozin 10mg daily was associated with a significantly increased risk of UTI compared to placebo (RR 1.33, 95% CI 1.10-1.61, I2 0%). SGLT-2 inhibitors were associated with a reduced risk of gastroenteritis (RR 0.38, 95% CI 0.20-0.72, I2 0%) but did not affect the risk of respiratory tract infections. 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.

Highlights

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel class of antihyperglycemic agents used in the treatment of type 2 diabetes mellitus
sodium-glucose cotransporter 2 (SGLT-2) inhibitors were studied as monotherapy or add-on therapy in comparison to placebo (65 randomized controlled trials (RCTs)), other active anti-diabetes agents (10 RCTs), or both placebo and active agent in combination (3 RCTs) or separately (8 RCTs)
sodium glucose co-transport (SGLT)-2 inhibitors were not associated with an increased risk of respiratory infections, including nasopharyngitis, pharyngitis, upper respiratory tract infection (URTI), bronchitis, and influenza

Summary

Introduction

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are a novel class of antihyperglycemic agents used in the treatment of type 2 diabetes mellitus. The Food and Drug Administration (FDA) has issued warnings about occurrences of ketoacidosis, acute kidney injury, urosepsis, and pyelonephritis during post-marketing studies of these drugs [8,9]. These findings are concerning given that patients with diabetes who develop genitourinary infections are vulnerable to poor health outcomes, hospitalization, and increased healthcare costs [10,11]. We conducted a systematic review and metaanalysis of RCTs to determine if the use of SGLT-2 inhibitors in patients with type 2 diabetes is associated with an increased risk of genitourinary and other site-specific infections

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