title: Frailty Attenuates the Impact of Metformin on Reducing Mortality in Older Adults with Type 2 Diabetes.
abstract: OBJECTIVE
  To determine whether the protective effect of metformin against death is modified by frailty status in older adults with type 2 diabetes.
  
  
  METHODS
  We conducted a cohort study during October 1, 1999-September 30, 2006 among veterans aged 65-89 years old with type 2 diabetes but without history of liver, renal diseases, or cancers, who had sulfonylureas or metformin as the sole antidiabetic drug for ≥180 days. The Cox proportional hazard model was used to compare hazard rates of all-cause mortality between the metformin and sulfonylurea users adjusting for the propensity score of metformin use and covariates: age, race/ethnicity, diabetes duration, Charlson comorbidity score, statin use, smoking status, BMI, LDL, and HbA1c.
  
  
  RESULTS
  In this cohort of 2,415 veterans, 307 (12.7%) were metformin users, 2,108 (87.3%) were sulfonylurea users, the mean age was 73.7±5.2 years, the mean study period was 5.6±2.3 years, the mean HbA1c at baseline was 6.7±1.0%, 23% had diabetes for ≥10 years, and 43.6% (N=1,048) died during the study period. For patients with and without frailty, the adjusted hazard ratio (HR) of death for metformin vs. sulfonylurea use were 0.92 (95% CI=0.90-1.31, p-value=0.19) and 0.69 (95% CI = 0.60-0.79, p-value<0.001), respectively. Logistic regression analyses showed that metformin (vs. sulfonylurea) was significantly associated with a decreased odds of frailty (OR: 0.66, 95% CI: 0.61-0.71, p-value <.0001).
  
  
  CONCLUSIONS
  Our study suggests that metformin could potentially promote longevity via preventing frailty in older adults with type 2 diabetes.
authors.affiliation: Department of Epidemiology & Biostatistics, University of Texas Health Science Center at San Antonio, USA ; Audie L Murphy Veterans Hospital, South Texas Veterans Health Care System, USA.
authors.forename: Chen-Pin
authors.initials: CP
authors.lastname: Wang
authors.affiliation: Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lorenzo
authors.affiliation: Department of Medicine, Division of Clinical Epidemiology, University of Texas Health Science Center at San Antonio, USA ; Department of Medicine, Division of Geriatrics, Gerontology, and Palliative Medicine, University of Texas Health Science Center at San Antonio, USA ; Geriatric Research Education and Clinical Center, Audie L Murphy Veterans Hospital, USA ; Barshop Institute for Longevity and Aging Studies, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Espinoza
keywords: Frailty; Metformin; Mortality; Type 2 diabetes