Risk of New-Onset Prostate Cancer for Metformin Versus Sulfonylurea Use in Type 2 Diabetes Mellitus: A Propensity Score–Matched Study

Authors: Yan Hiu Athena Lee MBChB1, Jiandong Zhou PhD2,3, Jeremy Man Ho Hui MBBS1,4, Xuejin Liu MSc5, Teddy Tai Loy Lee BPharm1,6, Kyle Hui MBBS1, Jeffrey Shi Kai Chan MBChB1, Abraham Ka Chung Wai MBChB6, Wing Tak Wong PhD7, Tong Liu MD, PhD8, Kenrick Ng PhD, MA, MBBChir, MRCP9, Sharen Lee MBChB1, Edward Christopher Dee MD10, Qingpeng Zhang PhD2, and Gary Tse MD, PhD1,8,11
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  • 1 Diabetes Research Unit, Cardiovascular Analytics Group, Hong Kong, China-UK Collaboration;
  • | 2 School of Data Science, City University of Hong Kong, Hong Kong, China;
  • | 3 Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;
  • | 4 Department of Medicine, School of Clinical Medicine, University of Hong Kong, Hong Kong, China;
  • | 5 School of Educational Science, Kaili University, Kaili City, Guizhou, China;
  • | 6 Department of Emergency Medicine, School of Clinical Medicine, University of Hong Kong, Hong Kong, China;
  • | 7 School of Life Sciences, Chinese University of Hong Kong, Hong Kong, China;
  • | 8 Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China;
  • | 9 Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London, United Kingdom;
  • | 10 Harvard Medical School, Boston, Massachusetts; and
  • | 11 Kent and Medway Medical School, Canterbury, Kent, United Kingdom.

Background: The aim of this study was to compare the risks of new-onset prostate cancer between metformin and sulfonylurea users with type 2 diabetes mellitus (T2DM). Methods: This population-based retrospective cohort study included male patients with T2DM presenting to public hospitals/clinics in Hong Kong between January 1, 2000, and December 31, 2009. We only included patients prescribed either, but not both, metformin or sulfonylurea. All patients were followed up until December 31, 2019. The primary outcome was new-onset prostate cancer and the secondary outcome was all-cause mortality. One-to-one propensity score matching was performed between metformin and sulfonylurea users based on demographics, comorbidities, antidiabetic and cardiovascular medications, fasting blood glucose level, and hemoglobin A1c level. Subgroup analyses based on age and use of androgen deprivation therapy were performed. Results: The final study cohort consisted of 25,695 metformin users (mean [SD] age, 65.2 [11.8] years) and 25,695 matched sulfonylurea users (mean [SD] age, 65.3 [11.8] years) with a median follow-up duration of 119.6 months (interquartile range, 91.7–139.6 months) after 1:1 propensity score matching of 66,411 patients. Metformin users had lower risks of new-onset prostate cancer (hazard ratio, 0.80; 95% CI, 0.69–0.93; P=.0031) and all-cause mortality (hazard ratio, 0.89; 95% CI, 0.86–0.92; P<.0001) than sulfonylurea users. Metformin use was more protective against prostate cancer but less protective against all-cause mortality in patients aged <65 years (P for trend <.0001 for both) compared with patients aged ≥65 years. Metformin users had lower risk of all-cause mortality than sulfonylurea users, regardless of the use of androgen deprivation therapy (P for trend <.0001) among patients who developed prostate cancer. Conclusions: Metformin use was associated with significantly lower risks of new-onset prostate cancer and all-cause mortality than sulfonylurea use in male patients with T2DM.

Submitted September 22, 2021; final revision received February 22, 2022; accepted for publication February 23, 2022.

Previous presentation: An abstract of this article has been accepted for presentation at the NCCN Annual Conference 2022; March 31–April 2, 2022.

Author contributions: Study concept and design: All authors. Software support: Zhou. Material preparation: Lee (Y.H.A.), Zhou, Hui (J.M.H.). Data collection and analysis: Lee (Y.H.A.), Zhou, Hui (J.M.H.). Supervision: Zhang, Tse. Writing – original draft: Lee (Y.H.A.), Zhou, Hui (J.M.H.). Writing – review and editing: All authors.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Dr. Edward Christopher Dee is funded in part through the Cancer Center Support Grant from the NCI (P30 CA008748).

Correspondence: Qingpeng Zhang, PhD, School of Data Science, Lau Ming Wai Academic Building, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong, China. Email: qingpeng.zhang@cityu.edu.hk; and Gary Tse, MD, PhD, FRCP, FFPH, Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China. Email: gary.tse@kmms.ac.uk

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