In subgroups of healthy, older men with type 2 diabetes, metformin therapy may reduce the likelihood of cardiovascular disease, cancer, depression, dementia and frailty-related diseases, although effects varied by individual risks for each condition, study findings show.
“We showed that metformin had differential effects on age-related comorbidities across classes,” Chen-Pin Wang, PhD, of the department of epidemiology and biostatistics at the University of Texas Health Science Center at San Antonio, and colleagues wrote.
“In particular, the effect of metformin on reducing a specific [age-related comorbidity] occurrence was the greatest in the class with the highest risk for that condition eg, the greatest reduction in CVD was found in the high CVD risk class, and these benefits appeared to further reduce mortality.”
Wang and colleagues analyzed data from 41,204 men aged at least 65 years with type 2 diabetes who were free from age-related comorbidities between 2002 and 2003, identified through the electronic medical records from the U.S. Veterans Administration (mean age, 75 years; mean Hba1c, 6.5%; 8,393 metformin users). Age-related comorbidities included cancer, dementia, CVD, depression and frailty-related conditions, including anemia, falls, weight loss, coagulopathy or gait disorder. Metformin exposure was classified as at least 180 days of prescription vs. no prescription. Researchers used latent class analysis to identify the distinct trajectory of age-related comorbidities and assessed the effects of metformin within each age-related comorbidity class. Logistic regression analysis was used to analyze log-odds of mortality associated with metformin use.
Researchers stratified the cohort by four age-related comorbidity trajectory classes: healthy class (53.6%), who had a lower likelihood of all age-related comorbidities; high-risk cancer class (11.6%); high-risk CVD class (17.6%); and high-risk frailty class (17.2%).
Among “healthy class” men, metformin use was associated with an absolute reduction of 2.77% in cancer, 6.1% in CVD, 5% in frailty-related disease, 0.9% in depression and 0.14% in dementia. In the high-risk cancer group, metformin therapy was associated with a 45.5% reduction in cancer, 13.3% reduction in CVD, 13.7% reduction in frailty-related disease and 5% reduction in depression. In the high-risk CVD group, metformin was associated with a 3.2% reduction in cancer diagnosis, 48.6% decrease in CVD, 6.3% decrease in frailty-related disease and a 2.8% decrease in depression. In the high-risk frailty group, metformin use was associated with a 3.9% decrease in cancer, 18.8% decrease in CVD, 23.8% decrease in frailty-related disease, 15.6% decrease in depression and 3.8% decrease in dementia.
Metformin therapy was also associated with a reduced mortality rate in all classes. The adjusted ORs for mortality associated with metformin use were 0.53 for the healthy group (95% CI, 0.5-0.57), 0.72 for the high-risk cancer group (95% CI, 0.62-0.83), 0.58 for the high-risk CVD group (95% CI, 0.52-0.64) and 0.39 for the high-risk frailty group (95% CI, 0.35-0.43).
“While the positioning of metformin among other glucose-lowering medications in terms of comorbidities and mortality prevention require further investigation,  this study provides important data for designing prospective studies aimed at examining the pleiotropic effects of metformin against other glucose-lowering medication on age-related comorbidities,” the researchers wrote.
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