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

Abstract

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.

Metformin use and mortality in Asian, diabetic patients with prostate cancer on androgen deprivation therapy: A population‐based study

“…Nonetheless, the data input was performed by the treating physicians, and none of the authors had influence over these inputs. In addition, the coding accuracy of the system was well demonstrated in other studies 11,13 …”

“…Causes of mortality were encoded using either ICD‐9 or ICD‐10 codes, depending on the year of death. This system has been used extensively for research 11–14 …”

Pharmacological Efficacy of Repurposing Drugs in the Treatment of Prostate Cancer

“…mTOR and acetyl-CoA carboxylase (ACC) inhibition blocks protein synthesis and fatty acid synthesis, respectively. Metformin also acts at the level of REDD1 (mTOR and cyclin D1 inhibitor) and inhibits GTPase Rac1, which leads to a reduction in PC metastases; inhibits the epithelial–mesenchymal transformation (EMT) process; decreases the expression c-MYC oncogene, SOX4 transcription factor and FoxM1 transcription factor, the latter two of which are associated with PC cell migration; increases miR30a expression (tumor suppressor); inhibits Pyruvate Kinase M2 (PKM2) phosphorylation and oxidation; and decreases the incidence of prostate intraepithelial lesions [ 21 , 22 ].…”

Dipeptidyl peptidase-4 inhibitors and mortality risks in patients with prostate cancer receiving androgen deprivation therapy: a population-based cohort study

“…Causes of mortality were encoded using ICD-9 or ICD-10, depending on the year of death. This system has been used extensively for research [12][13][14].…”

“…To the best of our knowledge, our study is the rst to directly compare the two treatment groups in PCa, suggesting possibly synergistic survival bene ts of DPP-4I and metformin. Indeed, the use of metformin has been associated with lower risks of new-onset PCa [12], but its interacting effects with DPP-4I on mortality in patients with established PCa need to be investigated in the future. Further in vivo experiments are needed to de nitively establish if there is any synergistic activity of these two drugs in treatment of PcC.…”