Effects of Intensive Lifestyle Intervention on All-Cause Mortality in Older Adults With Type 2 Diabetes and Overweight/Obesity: Results From the Look AHEAD Study

Background. Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5145 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.

Objective: 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 year 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.

Methods. Primary outcome was all-cause mortality from randomization to 16.7 years. Other outcomes included cause-specific mortality, interactions by sub-groups (age, sex, race/ethnicity, CVD history) and an exploratory analysis by magnitude of weight loss in ILI vs 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); 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, 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.