1998-LB: A Two-Year Trial of Metformin to Reduce Frailty in Older Adults with Glucose Intolerance

Introduction and Objective: Frailty is a major cause of morbidity and disability in older adults and insulin resistance is an important risk factor for frailty. We conducted a randomized, double blinded, placebo-controlled clinical trial of metformin in older adults (≥65 years) with glucose intolerance to determine its effect on frailty. Methods: Participants were randomized to 24 months of metformin (initiated at 500 mg/day and titrated to maximum tolerated dose up to 2,000 mg/day) or matching placebo. All participants received one session of diet and exercise counseling prior to initiation of study drug. The primary outcome was frailty as measured by the frailty index based on deficit accumulation model and frailty phenotype based on Fried criteria, which was assessed every 6 months. Using intention to treat, we conducted generalized estimating equations (GEE) models to examine the change in frailty per month by frailty index and Fried criteria. Results: One hundred forty-five participants were randomized; intention to treat analysis included 141 participants who took at least one dose of study drug. At baseline, participants were 48% female, 35% Hispanic/Latino, and mean age was 71.8 ±5.3 years. Metformin did not cause serious adverse events. Metformin led to a significant reduction in frailty progression rate per month assessed by frailty index compared to placebo (-0.0494 ±0.0216, 95%CI: -0.0918, -0.0071, p=0.0222). No difference was observed by Fried criteria (0.0116 ±0.0077, 95%CI: -0.0034, 0.0266, p=0.1302). Conclusion: Metformin administration to older adults with glucose intolerance may be useful for the prevention of frailty and extension of healthspan. Disclosure S.E. Espinoza: None. C. Wang: None. N. Musi: None. Funding National Institutes of Health (R01AG052697)