One Year of Exercise After Weight Loss Increases Postprandial GLP‐1 Secretion in Contrast to Usual Activity or GLP‐1 Receptor Agonist Treatment

Objective Incretin‐based obesity medication maintains weight loss by mimicking the appetite‐inhibiting hormone GLP‐1. Interestingly, chronic exercise may improve postprandial appetite control by increasing late postprandial secretion of endogenous GLP‐1. Therefore, we investigated whether an exercise program after weight loss could increase late‐phase postprandial GLP‐1 secretion. Methods This study is an exploratory analysis of adults with obesity ( n = 195) who lost 13.1 kg on a low‐calorie diet and were randomized to 52 weeks of either usual activity, moderate‐to‐vigorous intensity exercise, the GLP‐1 receptor agonist liraglutide (3.0 mg/day), or the combination. The primary endpoint was change in late‐phase GLP‐1 response to a 3‐h liquid mixed meal test before and after diet‐induced weight loss and after 1 year of intervention. Results Diet‐induced weight loss did not change late‐phase GLP‐1 response (3%; 95% CI, −4%–10%). One year of exercise increased late‐phase postprandial GLP‐1 response within the group by 37% (95% CI, 20%–57%), and this increase was 25% greater (95% CI, 3%–51%, p = 0.02) compared to the usual activity group. Late‐phase postprandial GLP‐1 response was unchanged in both groups treated with GLP‐1 receptor agonist compared to placebo. Conclusions One year of exercise increased late‐phase postprandial GLP‐1 response, which may prevent increased appetite after weight loss and thereby weight regain. Trial Registration EudraCT number: 2015–005585‐32; ClinicalTrials.gov identifier: NCT04122716