Updated: Jan 23
Adults with overweight or obesity who took semaglutide demonstrated short- and longer-term improvements in controlling their eating habits and substantial weight loss, according to the latest findings from the Semaglutide Treatment Effect in People with obesity (STEP) 5 trial. Over 104 weeks, participants who took semaglutide 2.4mg also improved participants' ability to resist food cravings, compared with placebo. The findings were revealed in the paper, ‘Two-year effect of semaglutide 2.4mg on control of eating in adults with overweight/obesity: STEP 5’, published in Obesity.
In STEP 5, adults with overweight/obesity were randomized 1:1 to semaglutide 2.4mg or placebo, plus lifestyle modification, for 104 weeks. Semaglutide was initiated at 0.25mg once weekly and escalated every four weeks to reach the maintenance dose of 2.4mg once weekly at the end of week 16 (±3 days visit window). Lower maintenance doses were permitted if participants were unable to tolerate 2.4mg.
Overall, mean changes in body weight from baseline to week 104 were −15.2% with semaglutide versus −2.6% with placebo (p<0.0001). From baseline to week 104, numerically larger proportions of participants in the semaglutide treatment group than in the placebo group achieved a weight loss of ≥5% (74.7% vs. 33.3%), ≥10% (57.8% vs. 10.1%), ≥15% (49.4% vs. 2.9%), and ≥20% (36.1% vs. 0.0%).
The trial included the Control of Eating Questionnaire (CoEQ) as an exploratory end point in a subpopulation of participants to assess the intensity and type of food cravings, as well as subjective sensations of appetite, hunger, fullness, and mood.
A 19-item CoEQ was administered at weeks 0, 20, 52, and 104 in a subgroup of participants. In participants completing the Control of Eating Questionnaire (semaglutide, n=88; placebo, n=86), mean body weight changes were −14.8% (semaglutide) and −2.4% (placebo). Scores significantly improved with semaglutide versus placebo for Craving Control and Craving for Savory domains at weeks 20, 52, and 104 (p<0.01); for Positive Mood and Craving for Sweet domains at weeks 20 and 52 (p<0.05); and for hunger and fullness at week 20 (p<0.001).
Improvements in craving domain scores were positively correlated with reductions in body weight from baseline to week 104 with semaglutide. At 104 weeks, scores for desire to eat salty and spicy food, cravings for dairy and starchy foods, difficulty in resisting cravings, and control of eating were significantly reduced with semaglutide versus placebo (all p<0.05).
Participant scores for difficulty in resisting cravings and difficulty in control of eating were significantly improved with semaglutide versus placebo from baseline to weeks 20, 52, and 104 (p<0.05 for both items at each time point). For the observed change over time in hunger, fullness, and difficulty resisting cravings, positive responses with semaglutide were observed early and then reached an equilibrium with placebo at the end of the study. For difficulty in control of eating, positive responses with semaglutide were observed early and remained improved compared with placebo to week 104.
In a post hoc analysis, reductions in body weight from baseline to week 104 in the semaglutide treatment group were numerically greater among participants with lower baseline Craving Control domain scores and among participants with higher baseline Craving for Savory and Craving for Sweet domain scores. In the placebo group, the opposite was seen for all three domains. The subgroup interaction was not significant for the Craving Control and Craving for Savory domain scores but was significant for Craving for Sweet domain scores (p < 0.05).
A post hoc analysis to assess whether baseline hunger and fullness scores influenced the amount of weight loss showed that, in the semaglutide group, reductions from baseline to week 104 in body weight were slightly greater (~1.0 percentage point) among participants who had more hunger (higher score) and less fullness (lower score) at baseline. In the placebo group, the opposite was seen.
For participants in the semaglutide treatment arm, those with ≥20% reduction in body weight felt less hungry and felt fuller at weeks 20, 52, and 104 compared with those with <20% reduction in body weight. At week 104 in the semaglutide treatment group, participants with a ≥20% reduction in body weight had a mean hunger score of 3.9 whereas those with <20% body weight reduction had a mean hunger score of 4.6. Mean scores for fullness were 6.8 for those with a ≥20% reduction in body weight and 6.1 for those with <20% body weight loss.
Semaglutide improves short- and longer-term control of eating, with participants reporting fewer cravings, reduced hunger, and increased feelings of fullness. In addition, semaglutide prevents the compensatory increases in appetite that would otherwise be expected after substantial weight loss. Together, these changes most likely underlie the marked and sustained weight loss effects seen with once-weekly semaglutide 2.4mg.
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