Urinary tract infection and continuation of sodium-glucose cotransporter-2 inhibitors in diabetic patients

Mei-Zhen Wu; Ran Guo; Chanchal Chandramouli; Lin Liu; Anthony Ma-On Tung; Christopher Tze-Wei Tsang; Yi-Kei Tse; Yap-Hang Chan; Chi-Ho Lee; Jia-Yi Huang; Jing-Nan Zhang; Wen-Li Gu; Qing-Wen Ren; Ching-Yan Zhu; Yik-Ming Hung; Carolyn S P Lam; Kai-Hang Yiu

doi:10.1093/eurheartj/ehaf788

Urinary tract infection and continuation of sodium-glucose cotransporter-2 inhibitors in diabetic patients

Eur Heart J. 2025 Oct 17:ehaf788. doi: 10.1093/eurheartj/ehaf788. Online ahead of print.

Authors

Mei-Zhen Wu^{1

2

3}, Ran Guo², Chanchal Chandramouli⁴, Lin Liu⁵, Anthony Ma-On Tung², Christopher Tze-Wei Tsang², Yi-Kei Tse², Yap-Hang Chan², Chi-Ho Lee⁶, Jia-Yi Huang², Jing-Nan Zhang², Wen-Li Gu², Qing-Wen Ren², Ching-Yan Zhu², Yik-Ming Hung², Carolyn S P Lam^{4

7

8}, Kai-Hang Yiu^{1

2}

Affiliations

¹ Division of Cardiology, Department of Medicine, the University of Hong Kong-Shenzhen Hospital, No. 1, Haiyuan 1st Road, Futian District, Shenzhen 518053, China.
² Division of Cardiology, Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Room 1928, Block K, Hong Kong, China.
³ Department of Geriatrics, National Key Clinical Specialty, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
⁴ National Heart Centre Singapore, Singapore, Singapore.
⁵ Department of Medicine, School of Clinical Medicine, the University of Hong Kong, Hong Kong, China.
⁶ Division of Endocrinology, Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
⁷ Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
⁸ Cardiovascular and Metabolic Disorders Programme, Duke-NUS Medical School, Singapore, Singapore.

PMID: 41104542
DOI: 10.1093/eurheartj/ehaf788

Abstract

Background and aims: To investigate the impact of incident urinary tract infection (UTI) and subsequent sodium-glucose cotransporter-2 (SGLT2) inhibitors discontinuation on clinical outcomes among patients with type 2 diabetes mellitus (T2DM) prescribed SGLT2 inhibitors.

Methods: This territory-wide cohort study analysed patients with T2DM prescribed SGLT2 inhibitors from January 2015 to June 2022. Primary outcomes included primary cardiovascular composite outcomes (heart failure hospitalization, stroke, myocardial infarction, or all-cause mortality) and primary renal composite outcomes (50% decline in estimated glomerular filtration rate [eGFR], end-stage renal failure, or all-cause mortality). The secondary outcome was recurrent UTI. A target trial emulation was applied to estimate the impact of discontinuing SGLT2 inhibitors.

Results: Among 61 606 eligible patients, 3921 (6.36%) had at least one UTI incidence during follow-up. Patients with incident UTI exhibited a higher risk of primary cardiovascular composite outcomes [hazards ratio (HR): 3.18, 95% confidence interval (CI): 2.88-3.51] and primary renal composite outcomes (HR: 2.51, 95% CI: 2.32-2.72) compared to those without UTI. Following a UTI, 32.31% of patients discontinued SGLT2 inhibitors. Discontinuation was associated with a higher cardiovascular (HR: 1.35, 95% CI: 1.20-1.53) and renal (HR: 1.35, 95% CI: 1.21-1.51) risks compared to continued use, while the risk of recurrent UTI was similar (HR: 0.96, 95% CI: 0.22-4.29).

Conclusions: New-onset UTI was associated with an increased risk of cardiovascular and renal events in patients with T2DM prescribed SGLT2 inhibitors. Discontinuing SGLT2 inhibitors after a UTI was linked to a higher risk of cardiovascular and renal outcomes but was not associated with fewer recurrent UTI.

Keywords: Prognosis; Sodium-glucose cotransporter-2 (SGLT2) inhibitors; Target trial emulation; Type 2 diabetes mellitus; Urinary tract infection.

Abstract

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