In Addition to Weight Loss, Semaglutide 2.4 mg Helps Control Appetite, Cravings

Using data from the STEP 5 trial, investigators provide new insight into the effects of semaglutide 2.4 mg on hunger and cravings among people with overweight and obesity, with results also shedding light on how these effects correlate to weight loss in the trial.

Sean Wharton, PharmD

Sean Wharton, PharmD

Results from an analysis of data from the pivotal STEP program suggest use of semaglutide 2.4 mg (Wegovy) could help people with overweight or obesity improve both short-term and long-term control of eating.

An analysis of data from the STEP 5 trial, results indicate use of the GLP-1 RA was associated with significant reductions in body weight and significantly improved scores for craving control, hunger and fullness, and difficulty resisting cravings in the trial.

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

Although semaglutide 2.4 mg has recently been placed in the spotlight of the general public with news of shortages and celebrity use, the GLP-1 receptor agonist has captivated the obesity and overweight management community for years, with excitement reaching a fever pitch in June 2021 when semaglutide 2.4 mg received approval from the US Food and Drug Administration. Although the community has looked to capture and apply the weight loss benefits of the agent, many questions still exist surrounding the exact mechanism of action that induces weight loss, which could aid in optimizing use if answered.

With this in mind, a team of investigators led by Sean Wharton, of McMaster University and the Wharton Weight Management Clinic, designed the current study to estimate the effects of semaglutide 2.4 mg on control of eating with up 2 years of treatment using data from the STEP 5 trial. A phase 3 trial comparing weekly semaglutide 2.4 mg against placebo for long-term treatment of obesity or overweight with at least 1 weight-related comorbidity, without diabetes, the trial enrolled and randomized 304 patients with a pair of co-primary endpoints assessing percentage change in body weight and achievement of a 5% or greater reduction of body weight at week 104.

In the current study, investigators sought to leverage data from a 19-item Control of Eating Questionnaire was administered at weeks 0, 20, 52, and 104 in a subgroup of participants from the trial. In total, 88 patients receiving semaglutide 2.4 mg and 86 receiving placebo had completed data from the Control of Eating Questionnaire, which was administered at weeks 0, 20, 52, and 104. Of the 19 items in the questionnaire, 17 assessed 4 domains, which were classified as Craving Control, Positive Mood, Craving for Savory, and Craving for Sweet, with the other items assessing a patient’s hunger level and how full they have felt.

At the conclusion of the 104-week trial, the mean body weight changes were -14.8% with semaglutide 2.4 mg and -2.4% with placebo among the subgroup of patients with Control of Eating Questionnaire data. Analysis of questionnaire data indicated use of semaglutide 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 fullness at week 20 (P <.001).

Further analysis indicated improvements in caring domain scores observed in the trial were positively correlated with reductions in body weight from baseline to week 104 with semaglutide 2.4 mg. Investigators also highlighted the 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).

“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 added.

This study, “Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5,” was published in Obesity.

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