TOPLINE

Adults with overweight or obesity receiving semaglutide 2.4 mg consumed significantly fewer calories at an “all-you-can-eat” laboratory lunch than those who received a placebo at weeks 20, 40, and 60 — even as early gains in self-reported appetite control and reductions in food preoccupation waned after week 20.

METHODOLOGY

• Short-term (≤ 20-week) studies show that semaglutide reduces energy intake, appetite, and response to food reward, but their limited duration leaves it unclear whether these changes persist and support long-term weight maintenance.
• Researchers conducted a 60-week randomized trial assigning 120 adults with overweight (with an obesity-related comorbidity) or obesity (mean age, 45.7 years; 78.3% women) to receive once-weekly subcutaneous semaglutide 2.4 mg or a matching placebo.
• Semaglutide was started at a dose of 0.24 mg/wk; the dose was increased every 4 weeks until it reached 2.4 mg/wk at week 16. All participants received standardized 15-minute lifestyle counseling sessions throughout the study.
• During laboratory visits at weeks 0, 20, 40, and 60, participants had energy intake measured during an ad libitum lunch, rated appetite while fasting and at 30-minute intervals for 4 hours after a standardized breakfast, and had food reward assessed via a standard questionnaire and a computerized food-choice task. Past-week appetite was assessed for hunger, fullness after meals, and food preoccupation.
• The primary outcome was the change from baseline in ad libitum energy intake at weeks 20, 40, and 60.

TAKEAWAY

• Semaglutide produced significantly larger reductions from baseline in ad libitum lunch energy intake than placebo at weeks 20, 40, and 60 (mean differences, 291.9 kcal, 240.2 kcal, and 269.5 kcal, respectively; adjusted P < .05 for all).
• At week 20, semaglutide produced greater improvements in fasting and postprandial appetite suppression and larger reductions in past-week hunger and food preoccupation (adjusted P < .05 for all); these between-group differences were smaller and no longer statistically significant at weeks 40 and 60.
• Reductions in responsiveness to the rewarding value of food remained significantly greater with semaglutide through week 40 (P = .0060) but not at week 60.
• By week 60, the mean weight loss was 15.1% vs 3.4% in the semaglutide group vs the placebo group; three serious adverse events occurred in the semaglutide group and none in the placebo group.

IN PRACTICE

“Patients’ willingness to continue to take an obesity management medication for weight-loss maintenance may wane if they believe that it is no longer working based on perceptions of diminished appetite control. Indeed, patients’ beliefs about medication effectiveness have been identified as a predictor of discontinuation. In light of these findings, patients could be counseled to expect a partial return of baseline appetite sensations after the first months of treatment, but, despite these changes, they will continue to eat less food. The continued reduction in food intake is required to maintain the new, reduced body weight, with its decreased energy requirements,” the authors of the study wrote.

SOURCE

The study was led by Jena S. Tronieri, Perelman School of Medicine, University of Pennsylvania, Philadelphia. It was published online in The American Journal of Clinical Nutrition.

LIMITATIONS

The placebo group had a higher dropout rate. Energy intake was assessed using only a single laboratory test meal. In addition, most participants were female, non-Hispanic, and White, limiting generalizability to other populations.

DISCLOSURES

The study was supported by a research grant from the Novo Nordisk Investigator Sponsored Studies Program. Several authors disclosed relationships with multiple companies, including investigator-initiated grants, consulting fees, research funding, and advisory board service.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.