Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis


https://doi.org/10.4081/aiua.2023.11509
Vol. 95 No. 2 (2023)
Published: June 13, 2023
Sodium glucose transporter 2 (SGLT2) inhibitors, Urinary tract infections, Genital infections, Candidiasis, Heart failure, Chronic kidney disease, Obesity
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Supplementary material: 64
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Authors

  • Rawa Bapir U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Smart Health Tower, Sulaymaniyah, Kurdistan region, Iraq.
  • Kamran Hassan Bhatti U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Urology Department, HMC, Hamad Medical Corporation, Qatar.
  • Ahmed Eliwa U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Department of Urology, Zagazig University, Zagazig, Sharkia, Egypt.
  • Herney Andrés García-Perdomo U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Universidad del Valle, Cali, Colombia.
  • Nazim Gherabi U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Faculty of Medicine Algiers 1, Algiers, Algeria.
  • Derek Hennessey U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Department of Urology, Mercy University Hospital, Cork, Ireland.
  • Vittorio Magri U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Urology Unit, ASST Fatebenefratelli Sacco, Milan, Italy.
  • Panagiotis Mourmouris U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; 2nd Department of Urology, National and Kapodistrian University of Athens, Sismanoglio Hospital, Athens, Greece.
  • Adama Ouattara U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Division of Urology, Souro Sanou University Teaching Hospital, Bobo-Dioulasso, Burkina Faso.
  • Gianpaolo Perletti U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Department of Biotechnology and Life Sciences, Section of Medical and Surgical Sciences, University of Insubria, Varese, Italy.
  • Joseph Philipraj U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Department of Urology, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth, Puducherry, India.
  • Konstantinos Stamatiou U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Department of Urology, Tzaneio General Hospital, 18536 Piraeus, Greece.
  • Musliu Adetola Tolani U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Division of Urology, Department of Surgery, Ahmadu Bello University/Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria.
  • Lazaros Tzelves U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; 2nd Department of Urology, National and Kapodistrian University of Athens, Sismanoglio Hospital, Athens, Greece.
  • Stefan D. Anker Department of Cardiology and BCRT (Campus CVK), Charité Universitätsmedizin Berlin, Germany.
  • Alberto Trinchieri
    alberto.trinchieri@gmail.com
    U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Urology School, University of Milan, Milan, Italy. https://orcid.org/0000-0002-9394-8292
  • Noor Buchholz U-merge Ltd. (Urology for emerging countries), London-Athens-Dubai; Sobeh's Vascular and Medical Center, Dubai Health Care City, Dubai, United Arab Emirates.

Although SGLT2 inhibitors have been initially employed in the treatment of type 2 diabetes, their clinical use was later extended to the treatment of other conditions such as heart failure, chronic kidney disease and obesity. In patients with type 2 diabetes, the administration of SGLT2 inhibitors has been associated with an increased incidence of urogenital infections, which may be linked to high glucose levels in the urine. The rate of urogenital side effects may be different in non-diabetic patients. The aim of this study was to review the risk of urogenital infections in non-diabetic patients taking SGLT2 inhibitors. Materials and methods: We conducted a systematic review and meta-analysis by searching PubMed and EMBASE for randomized controlled trials (RCTs) reporting urogenital adverse effects in non-diabetic patients treated with SGLT2 inhibitors. Odds ratios for urogenital infections were calculated using random effect Mantel-Haenszel statistics. Results: Out of 387 citations retrieved, 12 eligible RCTs were assessed for risk of bias and included in the meta-analysis. Compared to placebo, SGLT2 inhibitors were associated with increased odds of genital infections (OR 3.01, 95% CI: 1.93- 4.68, 9 series, 7326 participants, Z = 5.74, p < 0.0001, I2 = 0%) as well as urinary tract infections (OR 1.33, 95% CI: 1.13-1.57, 9 series, 7326 participants, Z = 4.05, p < 0.0001, I2 = 0%). When four trials investigating the effects of SGLT2 inhibitors in populations including both diabetic and non-diabetic patients were considered, administration of SGLT2 inhibitors in diabetic patients was associated with significantly higher odds of genital infections but not urinary tract infections compared to patients without type 2 diabetes. In patients taking placebo, the odds for urinary tract infections were significantly increased in diabetic patients compared to non-diabetic patients. Conclusions: The risk of genital infections is increased also in non-diabetic patients taking SGLT2 inhibitors although at a lesser extent that in diabetics. A careful assessment of the local anatomical conditions and of the history of previous urogenital infections is desirable to select those patients who need more intense follow-up, possibly combined with prophylactic measures of infections during treatment with SGLT2 inhibitors.


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Bapir, R., Bhatti, K. H., Eliwa, A., García-Perdomo, H. A., Gherabi, N., Hennessey, D., Magri, V., Mourmouris, P., Ouattara, A., Perletti, G., Philipraj, J., Stamatiou, K., Tolani, M. A., Tzelves, L., Anker, S. D., Trinchieri, A., & Buchholz, N. (2023). Risk of urogenital infections in non-diabetic patients treated with sodium glucose transporter 2 (SGLT2) inhibitors. Systematic review and meta-analysis. Archivio Italiano Di Urologia E Andrologia, 95(2). https://doi.org/10.4081/aiua.2023.11509

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