Semaglutide 2.4 mg cut food intake 35% in 20-week obesity trial

In a 20-week trial of 72 adults with obesity, once-weekly semaglutide 2.4 mg reduced how much participants ate at an unrestricted lunch by 35% compared with placebo, and participants reported less hunger and fewer food cravings ^[1]. The same study found no evidence that the drug slowed stomach emptying at week 20, which points to appetite control in the brain as the main reason people on the drug eat less ^[1].

The trial took place at a single center in Germany. Adults with obesity were randomly assigned to semaglutide or placebo, both given as once-weekly injections under the skin, for 20 weeks and 21 doses, followed by seven weeks of follow-up ^[1]. Semaglutide doses were escalated over time to reach 2.4 mg. The study is registered as NCT03842202 ^[1].

At week 20, participants were given a free-access lunch and could eat as much as they wanted. Those on semaglutide ate 1736 kilojoules, compared with 2676 kilojoules for those on placebo — an estimated treatment difference of 940 kilojoules (P < 0.0001) ^[1]. The paper reports energy intake in kilojoules.

Gastric emptying was the study's primary endpoint. It was measured indirectly, using paracetamol absorption after a standardized breakfast, rather than a direct scan. The paracetamol area under the curve from 0 to 5 hours was 8% higher with semaglutide than placebo (P = 0.005), but that difference was no longer statistically significant after the analysis was corrected for body weight at week 20 (P = 0.12). There was no effect on the 0-to-1-hour measure, peak paracetamol concentration, or time to peak concentration ^[1]. The authors concluded there was no evidence of delayed gastric emptying at week 20. They noted that a separate 12-week study of semaglutide 1.0 mg in people with obesity had indicated a delay in gastric emptying during the first hour ^[1].

Participants on semaglutide reported less hunger and lower prospective food consumption, and more fullness and satiety, than those on placebo (all P < 0.02). A control-of-eating questionnaire showed better control of eating and fewer or weaker food cravings (P < 0.05) ^[1]. Body weight fell by 9.9% with semaglutide and 0.4% with placebo ^[1]. The authors wrote that safety was consistent with the known profile of semaglutide ^[1].

The paper was published online on December 2, 2020, in the journal Diabetes, Obesity and Metabolism, volume 23, issue 3, pages 754–762 ^[1]. The study was funded by Novo Nordisk, and several authors are Novo Nordisk employees; one author is affiliated with Parexel International ^[1].

Why it matters for patients

The results describe a mechanism rather than a new treatment option. They quantify something many people on GLP-1 drugs report — eating less without counting or restricting — and they tie it to measurable changes in hunger, fullness and craving scores, not just to weight loss ^[1].

The gastric emptying finding has a practical edge. The paper notes that GLP-1 receptor agonists have been associated with delayed gastric emptying, which can affect how oral medicines taken at the same time are absorbed ^[1]. In this trial, at 20 weeks, the authors found no evidence of that delay ^[1]. That is one small study using an indirect measurement, and it does not settle how semaglutide interacts with other oral drugs in every patient.

The trial was phase 1, lasted 20 weeks and enrolled 72 people, so it does not show what happens over years, what happens after stopping the drug, or how semaglutide 2.4 mg compares with other obesity medications. None of that has been reported in this paper ^[1].

At the time of publication, semaglutide was approved for type 2 diabetes as a once-weekly injection up to 1.0 mg and a once-daily oral tablet up to 14 mg; the 2.4 mg dose was still in clinical development for weight management ^[1]. There are no findings here about dosing for individual patients.

What happens next

The paper states that once-weekly semaglutide 2.4 mg was being studied for weight management in the phase 3 STEP trial program ^[1]. The paper does not report when those results were expected, when the drug might be reviewed by regulators, or what further studies were planned ^[1].