Oral Semaglutide Shows Improved Energy Intake, Appetite, Eating Control in Adults with Obesity

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Findings from a double-blind study (NCT05236517) show that once-daily oral semaglutide at a dose of 50 mg lowered body weight, energy intake, and improved eating control in adults with obesity, with no evidence of gastric emptying through 20 weeks of treatment.¹

Semaglutide has been approved by the FDA in both long-acting injectable (Wegovy and Ozempic) and daily oral tablet (Rybelsus) formulations. In March 2024, Wegovy (semaglutide) was approved by the FDA to reduce the risk of major adverse cardiovascular events in adults with known heart disease and with obesity or overweight, in addition to a reduced calorie diet and increased physical activity.²

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist (RA), was initially approved in June 2021 for chronic weight management in those with obesity or overweight and at least one weight-related condition, including high blood pressure, type 2 diabetes, or high cholesterol, in addition to diet and increased exercise.³

“Semaglutide drives weight loss via multiple mechanisms, including reduced appetite, improved control of eating and reduced energy intake. Delayed gastric emptying is also a known effect of GLP-1 and GLP-1 analogues, and has been explored in studies with a duration of 12 weeks with QW s.c. semaglutide 1 mg and QD oral semaglutide 14 mg, using the paracetamol absorption technique,” the study authors wrote. “In these studies, semaglutide delayed gastric emptying during the first hour compared with placebo (reduction in the maximum observed paracetamol concentration [Cmax,para] and area under the concentration–time curve [AUC] for paracetamol from 0 to 1 hours [AUC0-1h,para] variables).”¹

Researchers conducted the study to analyze the effects of once daily oral semaglutide 50 mg on energy intake, appetite, eating control, and gastric emptying in patients with obesity over a period of 20 weeks. The clinical pharmacology, randomized, parallel-group, multiple-dose, double-blind, placebo-controlled trial was conducted from February 8, 2022, to November 7, 2022, at a single site in Germany. Energy intake was determined at an ad libitum lunch, with an evaluation conducted for participant-reported appetite ratings and Control of Eating Questionnaire responses. Investigators measured gastric emptying via paracetamol absorption after consuming a standardized breakfast.

Among 152 screened participants, 61 were randomly assigned to once daily oral semaglutide 50 mg (n = 30) or placebo (n = 31). A total of 54 participants (88.5%) completed the trial, including 28 of 30 participants from the once daily oral semaglutide 50 mg cohort (93.3%) and 26 of 31 in the placebo cohort (83.9%).

The results showed a relative change from baseline in ad libitum energy intake at week 20 of −39.2% points (95% confidence interval −59.0%, −19.4%) among participants administered semaglutide compared with placebo. Those in the semaglutide cohort experienced a decrease in body weight of 9.8% compared to 1.5% in the placebo cohort. Further, semaglutide was found to decrease hunger while increasing fullness and satiety, with fewer food cravings and superiority over placebo in eating control. Investigators did not find a statistically significant difference in gastric emptying at week 20.

In terms of safety, 25 of 30 participants in the semaglutide cohort reported adverse events (AEs) compared to 20 of 31 participants in the placebo cohort. The most frequently reported AEs in the semaglutide cohort were gastrointestinal disorders, with 107 AEs reported by 17 participants compared to 33 events reported by 10 participants in the placebo cohort. In terms of reported AEs, 50.0%, 36.7%, and 30.0% of participants in the semaglutide cohort reported nausea, diarrhea, and vomiting, respectively, compared to rates of 22.6%, 16.1%, and 6.5% of participants in the placebo cohort, respectively. All AEs were found to be transient, non-serious, and mild to moderate in severity.

“In conclusion, in participants with obesity, [once daily] oral semaglutide 50 mg reduced energy intake, appetite and food cravings, improved control of eating and was associated with clinically meaningful reductions in body weight at week 20,” the study authors wrote. “There was no evidence of delayed gastric emptying, as measured through paracetamol absorption. Additionally, the safety and tolerability profile was consistent with the known safety and tolerability profile of semaglutide and other GLP-1 RAs.”¹

References

1. Gabe MBN, Breitschaft A, Knop FK, et al. Effect of oral semaglutide on energy intake, appetite, control of eating and gastric emptying in adults living with obesity: A randomized controlled trial. Diabetes Obes Metab. 2024; 1-10. doi:10.1111/dom.15802

2. Wegovy® receives FDA approval for cardiovascular risk reduction in adults with known heart disease and overweight or obesity. Novo Nordisk. News release. March 8, 2024. Accessed July 31, 2024. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=167031

3. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014. FDA. News release. June 4, 2021. Accessed July 31, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014