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Age- and sex-specific risk of urogenital infections in patients with type 2 diabetes treated with sodium-glucose co-transporter 2 inhibitors: A population-based self-controlled case-series study

  • Minkyong Kang
    Affiliations
    College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea
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  • Kyu-Nam Heo
    Affiliations
    College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea
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  • Young-Mi Ah
    Affiliations
    College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongsangbuk-do, 38541, Republic of Korea
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  • Bo Ram Yang
    Correspondence
    Co-Corresponding at: College of Pharmacy, Chungnam National University, Daejeon, South Korea, 99 Daehak-ro, Yuseong-gu, Daejeon 34134.
    Affiliations
    College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea
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  • Ju-Yeun Lee
    Correspondence
    Corresponding author at: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
    Affiliations
    College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University 1, Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea
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      Highlights

      • Women aged 50 years or over administered sodium-glucose co-transporter 2 (SGLT2) for type 2 diabetes mellitus were at higher risk of genital infection and urinary tract infection.
      • The highest risk of urinary tract infection and genital infection was observed 8–14 days and 15–28 days after initiating SGLT2 inhibitor therapy, respectively.
      • The monitoring of urogenital infections in women aged over 50 years, especially during the first month after starting SGLT2 inhibitors, is recommended.

      Abstract

      This study aimed to investigate the age- and sex-specific risk of urogenital infections in patients with type 2 diabetes mellitus (T2DM) treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors. A self-controlled case series was conducted using annual national patient sample datasets from 2016 and 2017. Patients who were treated with SGLT2 inhibitors and who received antimicrobials for urogenital infections were included in the study. The incidence rate ratio (IRR) of urogenital infections during SGLT2 inhibitor exposure were compared with those in the non-exposure period. A total of 2,949 patients were included in the analysis, and 71.2% of the patients were women aged ≥ 50 years. Stratified analysis by age and sex showed that only women ≥ 50 years showed a significant increase in the risk of urinary tract infections (UTIs) (IRR 1.25, 95% CI 1.14–1.37) and genital infections (IRR 1.44, 95% CI 1.28–1.62). The highest risk of UTI risk was observed 8–14 days after initiating SGLT2 inhibitor therapy (IRR 1.49, 95% CI 1.07–2.08), and after 15–28 days for genital infections (IRR 2.11, 95% CI 1.66–2.67) in women ≥ 50. SGLT2 inhibitors increase the risk of urogenital infections in T2DM patients, especially in women aged ≥ 50 years. Monitoring of urogenital infections in women aged ≥ 50 years, especially during the first month after starting SGLT2 inhibitors, is recommended.

      Keywords

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      References

        • Anderson S.L.
        • Marrs J.C.
        Dapagliflozin for the Treatment of Type 2 Diabetes.
        Ann. Pharmacother. 2012; 46: 590-598
        • Jabbour S.A.
        • Goldstein B.J.
        Sodium Glucose Co-Transporter 2 Inhibitors: Blocking Renal Tubular Reabsorption of Glucose to Improve Glycaemic Control in Patients with Diabetes.
        Int. J. Clin. Pract. 2008; 62: 1279-1284
        • Wiviott S.D.
        • Raz I.
        • Bonaca M.P.
        Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes.
        N. Engl. J. Med. 2019; 380: 347-357
        • Zelniker T.A.
        • Wiviott S.D.
        • Raz I.
        Sglt2 Inhibitors for Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Cardiovascular Outcome Trials.
        Lancet North Am. Ed. 2019; 393 (10166): 31-39
        • Chaplin S.
        Sglt2 Inhibitors and Risk of Genitourinary Infections.
        Prescriber. 2016; 27: 26-30
        • Ellis A.K.
        • Verma S.
        Quality of Life in Women with Urinary Tract Infections: Is Benign Disease a Misnomer?.
        J. Am. Board Fam. Pract. 2000; 13: 392-397
      1. FDA, Drug Safety Communication: Fda Revises Labels of Sglt2 Inhibitors for Diabetes to Include Warnings About Too Much Acid in the Blood and Serious Urinary Tract Infections, F.d.c. letter, Editor. 2015.

        • Kim S.
        • Kim M.-S.
        • You S.-H.
        Conducting and Reporting a Clinical Research Using Korean Healthcare Claims Database.
        Korean J. Fam. Med. 2020; 41: 146
        • Petersen I.
        • Douglas I.
        • Whitaker H.
        Self Controlled Case Series Methods: An Alternative to Standard Epidemiological Study Designs.
        BMJ. 2016; 354: i4515
      2. Astellas, Suglat Tablets Drug Interview Form.2018.

      3. AstraZeneca Pharmaceuticals, L., Highlights of Prescribing Information of Farxiga(Dapagliflozin), for Oral Use. 2018.

      4. Boehringer Ingelheim Pharmaceuticals, I.Highlights of Prescribing Information of Jadiance(Empagliflozin) Tablets, for Oral Use. 2014.

        • Johnsson K.M.
        • Ptaszynska A.
        • Schmitz B.
        Vulvovaginitis and Balanitis in Patients with Diabetes Treated with Dapagliflozin.
        J. Diabetes Complications. 2013; 27: 479-484
        • Johnsson K.M.
        • Ptaszynska A.
        • Schmitz B.
        Urinary Tract Infections in Patients with Diabetes Treated with Dapagliflozin.
        J. Diabetes Complications. 2013; 27: 473-478
        • Liu X.-Y.
        • Zhang N.
        • Chen R.
        Efficacy and Safety of Sodium–Glucose Cotransporter 2 Inhibitors in Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials for 1 to 2 Years.
        J. Diabetes Complications. 2015; 29: 1295-1303
        • Lega I.C.
        • Bronskill S.E.
        • Campitelli M.A.
        Sodium Glucose Cotransporter 2 Inhibitors and Risk of Genital Mycotic and Urinary Tract Infection: A Population-Based Study of Older Women and Men with Diabetes.
        Diabetes Obesity Metab. 2019; 21: 2394-2404
        • Huang A.J.
        • Moore E.E.
        • Boyko E.J.
        Vaginal Symptoms in Postmenopausal Women: Self-Reported Severity, Natural History, and Risk Factors. 17. Menopause, New York, NY2010: 121
        • Li D.
        • Wang T.
        • Shen S.
        Urinary Tract and Genital Infections in Patients with Type 2 Diabetes Treated with Sodium-Glucose Co-Transporter 2 Inhibitors: A Meta-Analysis of Randomized Controlled Trials.
        Diabetes Obesity Metab. 2017; 19: 348-355
        • Engelhardt K.
        • Ferguson M.
        • Rosselli J.L.
        Prevention and Management of Genital Mycotic Infections in the Setting of Sodium-Glucose Cotransporter 2 Inhibitors.
        Ann Pharmacother. 2020; (1060028020951928)
        • Hammar N.
        • Farahmand B.
        • Gran M.
        Incidence of Urinary Tract Infection in Patients with Type 2 Diabetes. Experience from Adverse Event Reporting in Clinical Trials.
        Pharmacoepidemiol Drug Saf. 2010; 19: 1287-1292
        • Nyirjesy P.
        • Zhao Y.
        • Ways K.
        Evaluation of Vulvovaginal Symptoms and Candida Colonization in Women with Type 2 Diabetes Mellitus Treated with Canagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor.
        Curr Med Res Opin. 2012; 28: 1173-1178
        • Hirji I.
        • Andersson S.W.
        • Guo Z.
        Incidence of Genital Infection among Patients with Type 2 Diabetes in the Uk General Practice Research Database.
        J. Diabetes Complications. 2012; 26: 501-505