Differential effects of metformin on age related comorbidities in older men with type 2 diabetes

Aims To identify distinct temporal likelihoods of age-related comorbidity (ARC) diagnoses: cardiovascular diseases (CVD), cancer, depression, dementia, and frailty-related diseases (FRD) in older men with type 2 diabetes (T2D) but ARC naïve initially, and assess the heterogeneous effects of metformin on ARCs and mortality. Methods We identified a clinical cohort of male veterans in the United States who were ≥ 65 years old with T2D and free from ARCs during 2002–2003. ARC diagnoses during 2004–2012 were analyzed using latent class modeling adjusted for confounders. Results The cohort consisted of 41,204 T2D men with age 74.6 ± 5.8 years, HbA1c 6.5 ± 0.97%, and 8393 (20.4%) metformin users. Four ARC classes were identified. ‘Healthy Class’ (53.6%): metformin reduced likelihoods of all ARCs (from 0.14% in dementia to 6.1% in CVD). ‘High Cancer Risk Class’ (11.6%): metformin reduced likelihoods of CVD (13.3%), cancer (45.5%), depression (5.0%), and FRD (13.7%). ‘High CVD Risk Class’ (17.4%): metformin reduced likelihoods of CVD (48.6%), cancer (3.2%), depression (2.8%), and FRD (6.3%). ‘High Frailty Risk Class' (17.2%): metformin reduced likelihoods of CVD (18.8%), cancer (3.9%), dementia (3.8%), depression (15.6%), and FRD (23.8%). Conclusions Metformin slowed ARC development in old men with T2D, and these effects varied by ARC phenotype.