Objective: Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5,145 individuals with overweight/obesity and type 2 diabetes, found no significant differences in all-cause or cardiovascular mortality or morbidity during 9.6 (median) years of intervention. Participants in ILI who lost ≥10% at 1 year had lower risk of composite cardiovascular outcomes relative to DSE. Since effects of ILI may take many years to emerge, we conducted intent-to-treat analyses comparing mortality in ILI over 16.7 years (9.6 years of intervention and then observation) to DSE. In a secondary exploratory analysis, we compared mortality by magnitude of weight loss in ILI relative to DSE.
Research design and methods: Primary outcome was all-cause mortality from randomization to 16.7 years. Other outcomes included cause-specific mortality, interactions by subgroups (age, sex, race/ethnicity, and cardiovascular disease history), and an exploratory analysis by magnitude of weight loss in ILI versus DSE as reference. Analyses used proportional hazards regression and likelihood ratio.
Results: The incidence of all-cause mortality did not differ significantly in ILI and DSE (549 and 589 participants, respectively) (hazard ratio [HR] 0.91 [95% CI 0.81, 1.02]; P = 0.11). There were no significant differences between treatments in cause-specific mortality or within prespecified subgroups. ILI participants who lost ≥10% at 1 year had a 21% reduced risk of mortality (HR 0.79 [95% CI 0.67, 0.94]; P = 0.007) relative to DSE.
Conclusions: ILI focused on weight loss did not significantly affect mortality risk. However, ILI participants who lost ≥10% had reduced mortality relative to DSE.
© 2022 by the American Diabetes Association.