Effect of Obesogenic Medication on Weight‐ and Fitness‐Change Outcomes: Evidence from the Look AHEAD Study

Objective This study evaluates whether obesogenic medications may decrease the effectiveness of lifestyle interventions. The authors of this study hypothesized that participants who took obesogenic medications would be less responsive to the intervention in the Look AHEAD trial. Methods In the trial, 5,145 participants with overweight or obesity, aged 45 to 76 years with type 2 diabetes, were randomly assigned to an intervention (vs. support and education). In this analysis, the association of exposure to obesogenic medications and successful weight loss (≥5% and ≥10% of total weight) and fitness gain (≥1 and ≥2 metabolic equivalents) was examined. For each outcome, multiple logistic regression models were fitted. Results Analytic sample sizes were 4,496 for weight‐change analyses and 4,051 for fitness‐change analyses. After adjusting for covariates, exposure to one or more obesogenic medications significantly decreased the odds of achieving ≥5% weight loss by 32% (odds ratio [OR] 0.68) and achieving ≥10% weight loss by 19% (OR 0.81). The association was dose‐dependent—participants using two or more medications were less likely to achieve weight loss than those using one medication. Obesogenic medication exposure was not associated with decreased odds of achieving fitness gain overall. Conclusions The results suggest that exposure to obesogenic medications could hinder successful weight loss in a lifestyle intervention for people with diabetes.