Physical Activity and Weight Loss Among Adults With Type 2 Diabetes and Overweight or Obesity: A Post Hoc Analysis of the Look AHEAD Trial.

Importance: Prior findings from the Look AHEAD trial showed no significant reduction in the risk of cardiovascular events by lifestyle-induced weight loss among individuals with type 2 diabetes (T2D) and overweight or obesity. However, physical activity (PA) may modify the changes in cardiovascular risk associated with weight loss. Objective: To examine the joint association of weight loss and PA with the risk of adverse cardiovascular events in patients with T2D and overweight or obesity. Design, Setting, and Participants: This cohort study was a post hoc analysis of the Look AHEAD randomized clinical trial, which compared the cardiovascular effects of weight loss by intensive lifestyle intervention vs diabetes support and education among individuals with T2D and overweight or obesity. The study was conducted from June 2001 to September 2012, and participants were patients in the substudy of accelerometry-measured PA from 8 locations in the United States. Data were analyzed from June to August 2023. Exposures: Body weight change and accelerometer-derived PA volume across the first 4 years. Main Outcomes and Measures: The primary outcome was a composite cardiovascular outcome including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina. Results: Among a total of 1229 participants (mean [SD] age, 60 [7] years; 533 male [43%]), 333 (27%) achieved and maintained weight loss for the first 4 years. Among the individuals who maintained weight loss, 105 (32%) maintained high PA volume. During a median of 9.5 years of follow-up, 198 participants (16.1%) experienced the primary outcome. Compared with those with low PA volume and no weight loss (105 [15.8%]), maintaining high PA volume and weight loss was associated with a 61% lower risk of the primary end point (hazard ratio, 0.39; 95% CI, 0.19-0.81; P = .01). However, there was no significant difference in the risk of the primary end point among those with either weight loss only or high PA only. The multiplicative interaction between weight loss and PA for the risk of cardiovascular events was also significant (P for interaction = .01). Conclusions and Relevance: In this cohort study, maintaining weight loss and higher PA volume was associated with a lower risk of the composite cardiovascular outcome. The findings suggest that the cardiovascular benefits of PA may vary and be enhanced by weight loss among individuals with T2D and overweight or obesity.