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

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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.

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Acknowledgements

We wish to thank Mrs. Angella Lambrou, Liaison Librarian at the Life Sciences Library of McGill University, for her assistance in developing the database search strategies.

Funding

Drs. Filion and Azoulay are supported by Fonds de Recherche du Québec—Santé (FRQS) Junior II awards.

Author information

Authors and Affiliations

  1. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Robert Puckrin

  2. Deparment of Medicine, McGill University, Montreal, QC, Canada

    Marie-Philippe Saltiel & Kristian B. Filion

  3. Centre for Clinical Epidemiology, Lady Davis Institute, 3755 Cote Ste-Catherine Road, Suite H416.1, Montreal, QC, H3T 1E2, Canada

    Pauline Reynier, Laurent Azoulay & Kristian B. Filion

  4. Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada

    Laurent Azoulay

  5. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada

    Laurent Azoulay & Kristian B. Filion

  6. Division of Endocrinology, Jewish General Hospital, Montreal, QC, Canada

    Oriana H. Y. Yu

Authors
  1. Robert Puckrin
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  2. Marie-Philippe Saltiel
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  3. Pauline Reynier
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  4. Laurent Azoulay
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  5. Oriana H. Y. Yu
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  6. Kristian B. Filion
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Contributions

RP and MS conducted the literature search, performed data extraction, and assessed study quality. PR conducted the statistical analyses. RP wrote the manuscript. All authors interpreted data and revised the manuscript for important intellectual content. RP and KBF designed the study. KBF conceived of the study idea, supervised the study, and is the guarantor.

Corresponding author

Correspondence to Kristian B. Filion.

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Conflict of interest

The authors have no conflicts of interest to declare.

Ethical standard

This study used published, aggregate data and did not involve human participants or animals. Consequently, research ethics board review was not required.

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Not applicable

Additional information

Managed by Massimo Porta.

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Puckrin, R., Saltiel, MP., Reynier, P. et al. SGLT-2 inhibitors and the risk of infections: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol 55, 503–514 (2018). https://doi.org/10.1007/s00592-018-1116-0

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

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