Whether intentional weight loss reduces mortality in overweight/obese individuals with diabetes is unclear. Look AHEAD, a randomized trial of intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5145 individuals with overweight/obesity and type 2 diabetes, is ideal for examining this due to large sample, extended follow-up, excellent retention, and sustained difference in weight loss (y1: 8.6% ILI; 0.7% DSE; y10: 6.1% ILI; 3.9% DSE). After 10 years of intervention, participants had 6-month calls and biennial visits. The primary outcome for the current phase is all-cause mortality from randomization to 16 years. Data were analyzed with proportional hazards regression stratified by clinical site; significance was based on the likelihood ratio. All-cause mortality was 9% lower in ILI compared to DSE, not a statistically significant difference (Fig 1). Deaths by arm were: ILI 496/2570 and DSE 530/2575. Interactions of treatment with prespecified subgroups (sex, CVD history, age) were not significant. In post-hoc analyses, ILI participants who lost >10% at 1year had an 18% reduced risk (HR=.82, CI 0.68,0.97) and ILI participants who gained or lost <2% had a 29% higher risk (HR=1.29, CI 1.01,1.67) relative to all DSE. The difference in mortality between ILI and DSE was not statistically significant. Post-hoc analyses suggest an association between magnitude of weight change and all-cause mortality in ILI.

Disclosure

R.R. Wing: None. J. Clark: None. E.W. Gregg: None. S.B. Kritchevsky: None. C.E. Lewis: None. D.M. Reboussin: None. T.A. Wadden: Board Member; Self; Novo Nordisk Inc., Weight Watchers International, Inc. L.E. Wagenknecht: None. S.Z. Yanovski: None.

Funding

National Institutes of Health

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