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

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
• dapagliflozin
• empagliflozin
• genital infections
• GUI
• SGLT2i
• UTI

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors contributions

K Sridharan – conceived the study idea; K Sridharan, G Sivaramakrishnan – data collection; K Sridharan – data analysis and interpretation; K Sridharan – wrote the first draft of the manuscript; and K Sridharan, G Sivaramakrishnan – involved in revision and final approval of manuscript.

Acknowledgments

The author would like to thank Claude-Assistant^© for aiding in the grammar corrections in this manuscript.

Additional information

Funding

This paper was not funded.