Two-year Effect of Semaglutide 2.4 mg on Control of Eating in Adults with Overweight/Obesity: STEP 5

Abstract

Background: The STEP 5 trial (NCT03693430) investigated once-weekly (OW) subcutaneous semaglutide 2.4 mg vs placebo for the treatment of overweight/obesity in adults over 2 years. Methods: Adults w ith B MI ≥ 3 0 k g/m2, or ≥27 kg/m2 and ≥ 1 weight-related comorbidity, without diabetes, were randomized 1:1 to semaglutide 2.4 mg OW or placebo for 104 weeks. Co-primary endpoints related to body weight (BW) changes. Control of eating questionnaire (CoEQ) was assessed in a subgroup from Canada/USA, with scores from 19 individual items grouped into 4 domains: craving control, craving for savory, craving for sweet, or positive mood. P values for exploratory CoEQ data are unadjusted for multiplicity.Results: 304 adults were randomized (78% female; mean age 47 years, BW 106.0 kg and BMI 38.5 kg/m2). Semaglutide significantly reduced BW from baseline to week 104 vs placebo (estimated treatment difference: −12.6 %-points [95% CI: –15.3, –9.8]; p < 0.0001). In participants completing the CoEQ with semaglutide (n = 88) vs placebo (n = 86), all 4 domain scores significantly improved at week 20 and 52 (all p < 0.05). At week 104, craving control and craving for savory domains remained significantly improved with semaglutide vs placebo (p < 0.01); positive mood and craving for sweet were not statistically significant. Scores for the following individual craving-related items were significantly reduced from baseline with semaglutide vs placebo at week 104: desire to eat salty and spicy food, craving for dairy food, craving for starchy food, difficulty in resisting cravings, and difficulty in control of eating (all p < 0.05). Scores for hunger and fullness improved with semaglutide vs placebo at week 20, 52 and 104, but the differences were only significant at week 20 (p < 0.001 for both). Conclusions: In adults with overweight/obesity, substantial weight loss with semaglutide 2.4 mg was accompanied by short-and long-term improvements in control of eating vs placebo, with