The objective of this research was to examine the influence of metformin on both prognosis and adverse reactions in patients who have undergone radical cystectomy (RC) and subsequently received adjuvant gemcitabine and cisplatin (GC) chemotherapy for muscle-invasive bladder cancer (MIBC). A retrospective evaluation was performed on data from 243 patients who had undergone RC followed by adjuvant GC chemotherapy at the Affiliated Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, and Xuzhou Third People’s Hospital during the period from April 2014 to April 2024. The subjects were categorized into three categories based on metformin usage: non-diabetic (No DM), type 2 diabetic with metformin use (DM + Metformin), and type 2 diabetic without metformin use (DM-Metformin). Clinical and pathological characteristics were compiled and subjected to analysis. Progression-free survival (PFS) was assessed utilizing the Kaplan–Meier technique, while Cox proportional hazards models were employed for multivariable analysis. Among the 243 patients, diabetes was present in 68 individuals, of whom 51 were administered metformin. Pairwise comparisons revealed that diabetic patients receiving metformin exhibited significantly higher 3-year PFS rates compared to both diabetic patients not using metformin (23.6% vs. 7.2%, p = 0.007) and non-diabetic patients (23.6% vs. 13.4%, p = 0.034). In the multivariable analysis, metformin use was independently associated with a reduced risk of disease progression, both in the pooled analysis (Met vs. No Met: HR = 0.66, 95% CI 0.45–0.95, p = 0.025) and, most notably, in the direct comparison among diabetic patients (DM + Met vs. DM-Met: HR = 0.34, 95% CI 0.16–0.75, p = 0.007). Moreover, those administered metformin experienced a lower frequency of grade 3 or higher adverse reactions. This study provides clinical evidence suggesting that metformin use is associated with enhanced progression-free survival and a reduction in adverse reactions in patients receiving adjuvant GC chemotherapy after RC for MIBC. The beneficial association appears to be particularly pronounced in diabetic patients. These findings support the potential of metformin as an adjunctive therapy and justify further investigation in prospective trials.
Zhang et al. (Sat,) studied this question.