title: Differential effects of metformin on age related comorbidities in older men with type 2 diabetes.
abstract: OBJECTIVE
  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 ≥65years 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±5.8years, 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.
authors.affiliation: Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio; Geriatrics Research, Education & Clinical Center (GRECC), South Texas Veterans Health Care System. Electronic address: wangc3@uthscsa.edu.
authors.forename: Chen-Pin
authors.initials: CP
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lorenzo
authors.affiliation: Geriatrics Research, Education & Clinical Center (GRECC), South Texas Veterans Health Care System; Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio.
authors.forename: Samy L
authors.initials: SL
authors.lastname: Habib
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University.
authors.forename: Booil
authors.initials: B
authors.lastname: Jo
authors.affiliation: Geriatrics Research, Education & Clinical Center (GRECC), South Texas Veterans Health Care System; Department of Medicine, University of Texas Health Science Center at San Antonio; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Espinoza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D015331:Cohort Studies; D015897:Comorbidity; D003704:Dementia / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D003863:Depression / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D004351:Drug Resistance; D057286:Electronic Health Records; D016330:Frail Elderly; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D009026:Mortality; D009369:Neoplasms / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D015995:Prevalence; D012306:Risk; D014481:United States / Q000453:epidemiology; D014493:United States Department of Veterans Affairs; D058014:Veterans Health
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Comorbidity; Frailty; Metformin; Mortality; Type 2 diabetes