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1. Among US cancer survivors, metformin was associated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.

Evidence Rating Level: 1 (Excellent)

Cardiometabolic disease (CMD) is the leading cause of noncancer deaths in the cancer survivor (CS) population. Previous studies have found metformin to improve cardiometabolic status in populations with obesity, diabetes, or psychiatric disorders, potentially by inhibiting oxidative stress. However, the relationship between metformin use and cardiometabolic status in the CS population is limited. This prospective cohort study thus examined the association between metformin use and the risk of CMD / CMD-related mortality, as well as the role of the antioxidative stress mechanism in cancer survivors enrolled in the National Health and Nutrition Examination Survey. Among 3995 cancer survivors (weighted population = 21,671,061, weighted mean [SE] age = 62.62 [0.33] years; females = 2119 [53.04%]), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, 481 of which were from cardiometabolic causes. In the overall population of cancer survivors, metformin use was associated with a lower risk of all-cause (hazard ratio [HR] = 0.62; 95% CI, 0.47–0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44–0.97) mortality compared with metformin nonusers. Metformin use also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28–0.59), stroke (OR, 0.44; 95% CI, 0.26–0.74), hypertension (OR, 0.27; 95% CI, 0.14–0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21–0.78). These inverse associations, specifically metformin use and total CVD risk were also observed in patients with four specific cancer types identified as cardiometabolic high-risk, which included hematologic (OR, 0.29; 95% CI, 0.17–0.50), breast (OR, 0.42; 95% CI, 0.27-0.64), colorectal (OR, 0.32, 95% CI, 0.17-0.63) and prostate cancer (OR, 0.54; 95% CI 0.30-0.98). Individuals in the no metformin usage and high oxidative stress (OS) category displayed the highest risks of all-cause/cardiometabolic mortality and CMD, suggesting that metformin may antagonize oxidative stress. Overall, this study found that metformin use was associated with reduced risks of all-cause mortality, cardiometabolic disease, and associated mortality. Longitudinal studies are warranted to determine the practical application and pharmacological mechanisms of metformin in managing cardiometabolic health among the CS population.

Click to read the study in BMC Medicine

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