Appetite Regulation and Gastric Emptying of Semaglutide in Non-Diabetic Obese Adults: A Systematic Review

Abstract

Obesity is a chronic condition  driven in part by disrupted appetite control and changes in gastrointestinal function, both of which contribute to excessive energy intake and progressive weight gain. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to produce meaningful weight loss in non-diabetic adults. Despite its growing clinical use, the physiological processes through which semaglutide influences appetite and gastric emptying have not been clearly brought together. This systematic review explored how semaglutide affects appetite regulation and gastric emptying, and how these effects relate to weight reduction.<br /> A systematic search was conducted in PubMed, Google Scholar, and Dimensions for studies published between 2021 and 2026, in line with PRISMA 2020 guidelines. Study screening, data extraction, and risk-of-bias assessment were carried out using Covidence by two independent reviewers, with a third reviewer resolving any disagreements. Four studies met the inclusion criteria, consisting of randomized controlled trials and one retrospective cohort study.<br /> Across randomized trials, semaglutide was consistently associated with greater improvements in appetite-related outcomes compared with placebo, including reductions in hunger scores and overall energy intake. Studies that assessed gastric physiology reported a notable delay in gastric emptying with semaglutide, particularly during the early stages of treatment. These physiological changes occurred alongside greater weight loss in semaglutide-treated participants compared with control groups. Longer-term findings suggested that appetite suppression was maintained over time and accompanied by clinically meaningful weight reduction, while observational data supported the effectiveness of semaglutide in routine clinical practice.<br /> Overall, the findings suggest that the weight-reducing effects of semaglutide in non-diabetic adults with obesity are closely tied to its ability to suppress appetite and slow gastric emptying. These mechanisms appear to play a central role in its therapeutic benefits and help explain the sustained weight loss observed with treatment.