The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity

Abstract

Aim: To investigate the effects of once-weekly subcutaneous (s.c.) semaglutide 2.4 mg on gastric emptying, appetite, and energy intake in adults with obesity.

Materials and methods: A double-blind, parallel-group trial was conducted in 72 adults with obesity, randomized to once-weekly s.c. semaglutide (dose-escalated to 2.4 mg) or placebo for 20 weeks. Gastric emptying was assessed using paracetamol absorption following a standardized breakfast. Participant-reported appetite ratings and Control of Eating Questionnaire (CoEQ) responses were assessed, and energy intake was measured during ad libitum lunch.

Results: The area under the concentration-time curve (AUC) for paracetamol 0 to 5 hours after a standardized meal (AUC0-5h,para ; primary endpoint) was increased by 8% (P = 0.005) with semaglutide 2.4 mg versus placebo at week 20 (non-significant when corrected for week 20 body weight; P = 0.12). No effect was seen on AUC0-1h,para , maximum observed paracetamol concentration, or time to maximum observed paracetamol concentration. Ad libitum energy intake was 35% lower with semaglutide versus placebo (1736 versus 2676 kJ; estimated treatment difference -940 kJ; P <0.0001). Semaglutide reduced hunger and prospective food consumption, and increased fullness and satiety when compared with placebo (all P <0.02). The CoEQ indicated better control of eating and fewer/weaker food cravings with semaglutide versus placebo (P <0.05). Body weight was reduced by 9.9% with semaglutide and 0.4% with placebo. Safety was consistent with the known profile of semaglutide.

Conclusions: In adults with obesity, once-weekly s.c. semaglutide 2.4 mg suppressed appetite, improved control of eating, and reduced food cravings, ad libitum energy intake and body weight versus placebo. There was no evidence of delayed gastric emptying at week 20, assessed indirectly via paracetamol absorption.

Keywords: GLP-1 analogue; appetite; control of eating; energy intake; food craving; gastric emptying; glucagon-like peptide-1; obesity; randomized trial; semaglutide.

Conflict of interest statement

M.F., S.T. and D.S. are employees and shareholders of Novo Nordisk, the sponsor of this trial; A.W. is an employee of Novo Nordisk. A.B. is an employee of Parexel International GmbH; Parexel International GmbH was paid by Novo Nordisk for assistance in conducting the study.

© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Trial design. OW, once weekly; s.c. subcutaneous

FIGURE 2

Ad libitum lunch energy intake at week 20 (A) and change from baseline in ad libitum lunch energy intake at week 20 (B). Estimates were calculated from analysis of covariance (ANCOVA) models using baseline energy intake of 3313 kJ, which corresponds to the average baseline value for all participants (semaglutide and placebo groups) who contributed to the analysis. ‡Obtained from an ANCOVA model with energy intake at baseline as a covariate and treatment as a factor. †Obtained from an ANCOVA model with change from baseline value to week 20 as response, energy intake at baseline as a covariate and treatment as a factor. CI, confidence interval; ETD, estimated treatment difference; s.c., subcutaneous

FIGURE 3

Postprandial appetite ratings after standardized breakfast at week 20. Overall appetite suppression score calculated as: (satiety + fullness + [100 – hunger] + [100 – prospective food consumption]) / 4. Each endpoint was analysed using the analysis of covariance model with baseline value of the respective endpoint as covariate and treatment as factor. The figure shows the estimated treatment difference for semaglutide versus placebo (boxes) and 95% confidence interval (whiskers). CI, confidence interval; ETD, estimated treatment difference; VAS, visual analogue score

FIGURE 4

Control of eating and food cravings evaluated by the Control of Eating Questionnaire visual analogue scale at week 20. The Control of Eating Questionnaire was completed by participants at the end of the 20‐week treatment period (day 141), based on their experience over the prior 7 days. Individual scores for each question were analysed using separate analysis of covariance models with change from baseline as response, baseline value of respective question as a covariate and treatment as factor (post hoc analysis methodology). The figure shows the estimated treatment difference (ETD) for semaglutide versus placebo (boxes) and 95% confidence interval (whiskers)