Association Between Metformin Use and Mortality Among Individuals With Non-Small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors: A Retrospective Cohort Study.

Abstract

Metformin has the potential to synergistically enhance the effect of immune checkpoint inhibitors (ICI) in nonsmall cell lung cancer (NSCLC). We evaluated the association between metformin use before ICI initiation and cancer-specific and all-cause mortality among NSCLC patients. We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2013-2019), including NSCLC patients with type 2 diabetes who newly initiated ICI therapy and had prior antidiabetic medication use. The exposure was metformin monotherapy versus sulfonylurea and/or dipeptidyl peptidase-4 (DPP-4) inhibitors. The primary outcome was cancer-specific mortality, and the secondary outcome was all-cause mortality. We used stabilized inverse probability of treatment weighting (sIPTW) to adjust for confounders. Fine-Gray competing risk model estimated cancer-specific mortality, while Cox proportional hazards model evaluated all-cause mortality. We included 1123 metformin users and 362 sulfonylurea/DPP-4 users. Although baseline characteristics differed, groups were well balanced after weighting. The adjusted incidence rate (aIR) of cancer-specific mortality was 82 versus 81 (aIR difference=1, 95% CI: -13 to 16), and all-cause mortality was 71 versus 67 (aIR difference=4, 95% CI: -6 to 15) per 100 person-years for metformin and sulfonylurea/DPP-4 users, respectively. Metformin use was not significantly associated with cancer-specific mortality (adjusted hazard ratio (aHR)=1.08, 95% CI: 0.88-1.33) and all-cause mortality (aHR=1.07, 95% CI: 0.90-1.26). In this large, diverse cohort of individuals with NSCLC using ICI, there was no statistically significant association between metformin use and cancer-specific or all-cause mortality.