Robert Puckrin1, Marie-Philippe Saltiel2, Pauline Reynier3, Laurent Azoulay3,4,5, Oriana H Y Yu6, Kristian B Filion7,8,9. 1. Department of Medicine, University of Toronto, Toronto, ON, Canada. 2. Deparment of Medicine, McGill University, Montreal, QC, Canada. 3. Centre for Clinical Epidemiology, Lady Davis Institute, 3755 Cote Ste-Catherine Road, Suite H416.1, Montreal, QC, H3T 1E2, Canada. 4. Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada. 5. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. 6. Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada. 7. Deparment of Medicine, McGill University, Montreal, QC, Canada. kristian.filion@mcgill.ca. 8. Centre for Clinical Epidemiology, Lady Davis Institute, 3755 Cote Ste-Catherine Road, Suite H416.1, Montreal, QC, H3T 1E2, Canada. kristian.filion@mcgill.ca. 9. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada. kristian.filion@mcgill.ca.
Abstract
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, 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 10 mg 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. 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.
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, 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 10 mg 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. 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.
Entities:
Keywords:
Adverse events; Infections; Sodium–glucose co-transporter 2 (SGLT-2) inhibitors; Systematic review and meta-analysis; Type 2 diabetes mellitus
Authors: Sruthi Adimadhyam; Glen T Schumock; Gregory S Calip; Daphne E Smith Marsh; Brian T Layden; Todd A Lee Journal: Br J Clin Pharmacol Date: 2018-11-08 Impact factor: 4.335
Authors: Chintan V Dave; Sebastian Schneeweiss; Dae Kim; Michael Fralick; Angela Tong; Elisabetta Patorno Journal: Ann Intern Med Date: 2019-07-30 Impact factor: 25.391
Authors: Giuseppe Defeudis; Rossella Mazzilli; Marta Tenuta; Giovanni Rossini; Virginia Zamponi; Soraya Olana; Antongiulio Faggiano; Paolo Pozzilli; Andrea M Isidori; Daniele Gianfrilli Journal: Diabetes Metab Res Rev Date: 2021-09-21 Impact factor: 8.128
Authors: E G Dorsey-Treviño; J G González-González; N Alvarez-Villalobos; V González-Nava; B M Contreras-Garza; A Díaz González-Colmenero; G Rodríguez-Tamez; F J Barrera-Flores; A M Farrell; V M Montori; R Rodriguez-Gutierrez Journal: J Endocrinol Invest Date: 2019-09-05 Impact factor: 4.256