Friedrichsen · Diabetes, obesity & metabolism 2021 · randomized controlled trial · n=72

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

Cited 405 times in the scientific literature.

Level 2 - randomized trial

Double-blind randomized controlled trial

PubMed 33269530 · doi:10.1111/dom.14280 · record verified 2026-08-31

What was done

A double-blind, parallel-group trial randomized 72 adults with obesity to once-weekly subcutaneous semaglutide (dose-escalated to 2.4 mg) or placebo for 20 weeks. Gastric emptying was evaluated via paracetamol absorption kinetics after a standardized breakfast. Subjective appetite ratings, Control of Eating Questionnaire (CoEQ) scores, ad libitum lunch energy intake, and body weight changes were measured.

What was found

Paracetamol AUC 0-5h was 8% higher with semaglutide versus placebo (P = 0.005), which became non-significant after adjusting for week 20 body weight (P = 0.12); paracetamol AUC 0-1h, Cmax, and Tmax were unchanged. Ad libitum energy intake at lunch was 35% lower with semaglutide compared to placebo (1736 kJ vs 2676 kJ; estimated treatment difference -940 kJ; P < 0.0001). Semaglutide reduced hunger and prospective food consumption, increased fullness and satiety (all P < 0.02), and reduced food cravings and improved control of eating (P < 0.05). Body weight decreased by 9.9% with semaglutide versus 0.4% with placebo.

Why it matters

It confirms that the substantial weight reduction observed with semaglutide 2.4 mg is primarily driven by reduced voluntary energy intake and appetite suppression rather than sustained slowing of gastric emptying at steady state.

Limits

The sample size was relatively small (72 participants), energy intake was measured at a single laboratory test meal rather than under free-living conditions, and gastric emptying was measured indirectly through paracetamol absorption rather than scintigraphy.

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