Semaglutide 2.4 mg Sustains Long-term Weight Loss by Reducing Cravings, Appetite: New Analysis

An analysis of data on long-term use of semaglutide 2.4 mg found the glucagon-like peptide 1 receptor agonist (GLP-1 RA) was not only associated with significant weight loss in persons with obesity but also with significantly improved scores on measures of craving control and hunger and fullness.

The combination of effects, according to investigators, appears to support the significant and sustained weight loss observed in the pivotal 104-week STEP 5 clinical trial, the STEP program study designed specifically to investigate longer-term weight management outcomes with semaglutide 2.4 mg.

“Semaglutide improves short- and longer-term control of eating, with participants reporting fewer cravings, reduced hunger, and increased feelings of fullness,” wrote investigators in the journal Obesity. “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 2.4 mg.”

Semaglutide 2.4 mg was approved by the US Food and Drug Administration in June 2021 as an adjunctive treatment to lifestyle recommendations to support and maintain weight loss in adults with obesity and overweight. Subsequent approval for the same indication in adolescents was awarded in January 2023.

Authors of the current study state that in previous clinical studies of up to 20 weeks in persons with obesity, semaglutide 2.4 mg was shown to reduce body weight by improving aspects of control of eating, including reducing appetite, food cravings, and energy intake.

Incentive for this study was interest in understanding semaglutide's longer-term effects on control of eating and particularly in the setting of substantial weight loss.

First author Sean Wharton, of McMaster University and the Wharton Weight Management Clinic, and colleauges tapped 2 years of treatment data with semaglutide 2.4 mg from the pivotal phase 3 STEP 5 clinical trial. STEP 5 compared semaglutide with placebo for long-term treatment of obesity or overweight in persons with at least 1 weight-related comorbidity and without diabetes. A total of 304 participants were enrolled and randomized to receive active drug or placebo and all received the same lifestyle intervention. The study’s coprimary endpoints were percentage change in body weight at week 104 and achievement of a ≥5% reduction in body weight at week 104.

For the current study, investigators evaluated STEP 5 data from a 19-item version of the Control of Eating Questionnaire (CoEQ) administered to a subgroup of trial participants at weeks 0, 20, 52, and 104.

FINDINGS

In total, 174 participants from STEP 5 completed the CoEQ (semaglutide 2.4 mg, n=88; placebo, n= 86). Mean age of the group was 47 years, 77.6% were women, and 88.5% were White. Mean body weight was 106.5 (23.6) kg.

Of the 19 CoEQ items, 17 assessed 4 domains classified as Craving Control, Positive Mood, Craving for Savory, and Craving for Sweet, with the 2 other items assessing a patient’s hunger level and level of satiety.

Wharton et al report that at week 104, the mean body weight changes were -14.8% with semaglutide 2.4 mg and -2.4% with placebo. The investigators found that treatment with semaglutide 2.4 mg was associated with significantly improved scores for Craving Control and Craving for Savory domains at weeks 20, 52, and 104 (P <.01), for Positive Mood and Craving for Sweet domains at weeks 20 and 52 (P <.05), and for both hunger and satiety at week 20 (P <.001).

Importantly the analysis indicated that improvements in craving domain scores were positively correlated with reductions in body weight from baseline to week 104 in participants treated with semaglutide 2.4 mg. 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 (P for all <.05).

Importantly the analysis indicated that improvements in craving domain scores were positively correlated with reductions in body weight from baseline to week 104 in participants treated with semaglutide 2.4 mg

“Our results suggest that different aspects of control of eating were operative during initial weight loss (early time points) and weight loss maintenance (later time point) with semaglutide treatment, and that an overall reduction in food cravings and craving for savory food was in effect throughout. These effects on control of eating were associated with ~15% weight loss and the maintenance of that weight loss up to104 weeks,” investigators wrote. “Semaglutide improves short- and longer-term control of eating,” they added.

The study’s primary strength, write Wharton and colleagues, is its duration. At 104 weeks it is now the longest longitudinal assessment of the effect of semaglutide 2.4 mg on control of eating. Limitations include the potential for false-positive findings as a result of the many multiple comparisons made. Also, generalizability of the findings to the larger trial sample from this subgroup is unknown.

Reference: Wharton S, Batterham RL, Bhatta M, et al. Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/ obesity: STEP 5. Obesity. Published online January 18, 2023. doi:10.1002/oby.23673