OBJECTIVES: Despite promising laboratory findings, clinical evidence on the protective potential of metformin against carfilzomib-induced cardiotoxicity remains lacking. This study evaluates the real-world effectiveness of metformin in reducing major adverse cardiac events (MACE) in multiple myeloma (MM) patients with type 2 diabetes mellitus (T2DM) receiving carfilzomib treatment, using a nationwide cohort.

METHODS: We conducted a retrospective cohort study using the Health Insurance Review and Assessment database from 2007 to 2022. Adult MM patients with T2DM who initiated carfilzomib regimens were included. Those with advanced chronic kidney disease or a recent history of MACE were excluded. Metformin users were defined as patients who had at least one prescription both within 6 months prior to and during carfilzomib treatment; non-users had no prescriptions in this period. Inverse probability treatment weighting was used to adjust for baseline differences. The endpoints were time to first MACE and its individual components—acute myocardial infarction, ischemic stroke, heart failure, or cardiovascular death—during the carfilzomib treatment period. Subdistribution hazard ratios (HRs) were estimated using the Fine-Gray model, accounting for competing mortality risks.

RESULTS: A total of 439 MM patients with T2DM were treated with carfilzomib. The incidence of MACE per 100 person-year was 22.8 in metformin users (n=294) and 26.3 in non-users (n=145). Metformin use did not significantly reduce the incidence of MACE (HR 0.861; 95% CI 0.628–1.180). Although no significant differences were observed in individual components of MACE either, it is notable that there was a borderline significant reduction in heart failure risk, with an HR of 0.694 (p=0.057).

CONCLUSIONS: Our findings do not support a significant cardioprotective effect of metformin in reducing overall MACE incidence in MM patients with T2DM on carfilzomib but suggest a potential for reducing heart failure risk.