Association of Intensive Lifestyle Intervention and Metformin with Frailty in the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS)

Abstract

Objective: To examine whether odds of frailty differ by DPP intervention arms (intensive lifestyle intervention [ILS], metformin [MET], placebo [PLB] after long-term follow-up in the DPPOS. Methods: DPP, a randomized trial of individuals at high risk of diabetes, lasted 2.8 years, after which there was a 13-month bridge period in which 16 sessions of group ILS was offered to all participants. During DPPOS, ILS was offered lifestyle reinforcement semi-annually and MET received unmasked metformin. Frailty was measured initially in DPPOS Year 8 in 2385 participants and repeated in 2264 of these in Year 10 (12 and 14 years after randomization). Using Fried criteria, presence of 3 of 5 characteristics (slow walking speed, weak grip strength, unintentional weight loss, low physical activity, and exhaustion) was classified as frail, 1 or 2 pre-frail, and 0 non-frail.: GEE models adjusting for visit year were employed with repeated measures pooled from Years 8 and 10 to estimate pairwise odds ratios between ILS, MET and PLB for the outcomes of frail and pre-frail vs. non-frail. Results: Odds of frailty vs. non-frailty were 37% lower in ILS compared to PLB (Table) and MET (OR=0.629, CI= 0.420-0.942, p=0.024). There were no significant treatment group differences in odds of pre-frailty. Conclusion: ILS intervention in persons at high risk of diabetes may reduce frailty in later life.12 years Post-randomization14 years post-randomizationOdds of Frailty vs. Non-Frailty Pooled over both examsTreatment GroupPrevalencePrevalence OR (95% CI) compared with placeboP-valuePre-FrailtyFrailtyPre-FrailtyFrailtyPlacebo42.8%5.7%43.7%5.4%1 (referent)n/aMetformin45.8%5.4%42.5%5.3%0.994 (0.694-1.424)0.976Lifestyle46.8%3.0%46.3%3.6%0.625 (0.419-0.934)0.022 Disclosure H.P. Hazuda: None. Q. Pan: None. J.P. Crandall: None. H. Florez: Advisory Panel; Self; Sanofi. J.A. Luchsinger: None. E.M. Venditti: None. A. Kriska: None. S. Golden: None. G. Bray: Advisory Panel; Self; Herbalife International of America, Inc., Novo Nordisk A/S. D. Research Group: None.