Metformin Against Herpes Zoster in Colon Cancer Patients with Type 2 Diabetes: A PSM Analysis

<b>Background:</b> Herpes zoster is a significant complication in cancer patients, particularly those with compromised immune systems. Previous studies have established the incidence of herpes zoster in gastrointestinal cancer patients, but there is a lack of specific analysis on colorectal cancer patients and the potential preventive role of metformin. This study aims to fill this gap by evaluating metformin's protective effects against herpes zoster in colon cancer patients with type 2 diabetes mellitus (T2DM). <b>Methods:</b> The study cohort comprised 1,510 T2DM colon adenocarcinoma patients without distant metastasis who received standard treatments from Taiwan Cancer Registry Database. Propensity score matching (PSM) was employed to balance covariates between metformin users and nonusers. Herpes zoster infection risk was assessed using Cox regression models and incidence rate calculations. The dose-dependent effects of metformin were analyzed based on cumulative defined daily doses (cDDD). <b>Results:</b> Metformin use was associated with a significantly reduced risk of herpes zoster infection (adjusted hazard ratio [aHR].: 0.69, 95% confidence interval [CI].: 0.51 to 0.93). A dose-dependent relationship was observed, with progressively lower aHRs across cDDD quartiles (p for trend < 0.0001). After adjusting for competing mortality risks, the aHR remained significantly lower (aHR: 0.70, 95% CI: 0.51 to 0.65). Metformin users had lower incidence rates and incidence rate ratios (IRR) of herpes zoster infection compared to nonusers (IRR: 0.75, 95% CI: 0.56 to 0.97). <b>Conclusions:</b> We are the first to demonstrate a dose-dependent protective effect of metformin against herpes zoster in colorectal cancer patients. Our findings indicate that higher doses of metformin correlate with a greater reduction in the risk of herpes zoster.