Genito-urinary infectious adverse events related to sodium glucose cotransporter-2 inhibitors: a network meta-analysis and meta-regression

Expert Rev Clin Pharmacol. 2024 May-Jun;17(5-6):515-524. doi: 10.1080/17512433.2024.2355287. Epub 2024 May 16.

Abstract

Introduction: Sodium glucose cotransporter-2 inhibitors (SGLT2is) are an emerging class of drugs with wide indications. Controversial evidence exists regarding the risk of urinary tract infection (UTI) and genital infections (GI) with SGLT2is paving way for undertaking this network meta-analysis and meta-regression study.

Methods: Data from randomized trials evaluating SGLT2is reporting the number of patients with UTI and GI were included. Odds ratios (OR) with 95% confidence intervals (95% CI) were the effect estimates. Meta-regression analysis identified risk factors. Number needed to harm (NNH) was estimated.

Results: Two hundred and sixty-four articles were included [UTI (213 studies; 150,140 participants) and GI (188 studies; 121,275 participants)]. An increased risk of UTI (OR: 1.11; 95% CI: 1.06, 1.16) and GI (OR: 3.5, 95% CI: 3.1, 3.9) was observed. Men showed a lower risk of UTI (OR: 0.2; 95% CI: 0.2, 0.3) and GI (OR: 0.4; 95% CI: 0.4, 0.5). Meta-regression analyses revealed BMI ≥ 30 kg/m2 and duration of SGLT2i treatment for ≥6 months as risk factors. NNH was 16 for UTI and 25 for GI.

Conclusion: SGLT2is increase the risk of UTI and GI that needs to be incorporated in the treatment guidelines with precautions in high-risk patients.

Prospective protocol registration: https://osf.io/5fwyk.

Keywords: Canagliflozin; GUI; SGLT2i; UTI; dapagliflozin; empagliflozin; genital infections.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy
  • Female
  • Humans
  • Male
  • Network Meta-Analysis
  • Randomized Controlled Trials as Topic*
  • Regression Analysis
  • Reproductive Tract Infections* / chemically induced
  • Reproductive Tract Infections* / epidemiology
  • Risk Factors
  • Sex Factors
  • Sodium-Glucose Transporter 2 Inhibitors* / administration & dosage
  • Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
  • Urinary Tract Infections* / drug therapy

Substances

  • Sodium-Glucose Transporter 2 Inhibitors