Management of obesity with semaglutide or metformin in patients with antipsychotic-induced weight gain (MOSA): a non-randomised open-label pilot study

Background: Antipsychotic-induced weight gain (AIWG) represents a significant clinical challenge for both patients and clinicians, requiring appropriate interventions to prevent or reverse weight gain in patients using antipsychotics. Glucagon-like peptide 1 (GLP-1) agonists represent a novel approach to the management of obesity that has recently attracted considerable attention. Semaglutide (a GLP-1 agonist) has been demonstrated to result in notable weight loss. The present study investigates whether semaglutide is equally effective in achieving weight loss in patients with AIWG.

Methods: A prospective, non-randomised cohort study was conducted with the objective of evaluating the efficacy and safety of oral semaglutide for the treatment of AIWG in routine outpatient clinical practice. Subsequently, the results were compared with those of a control group of AIWG patients taking metformin.

Results: After 16 weeks, the mean body weight loss was 4.5 kg (95% confidence interval (CI), -6.7 to -2.3 kg; p < 0.001) in the semaglutide group (n = 10) versus 2.9 kg (95% CI, -4.5 to -1.4 kg; p < 0.001) in the metformin group (n = 26). This corresponds to an average body weight loss of 4% for semaglutide, and 2.5% for metformin. The respective reductions in body mass index (BMI) and waist circumference were -1.7 kg/m2 (95% CI, -2.4 to -1.0 kg/m2; p < 0.001) and -6.8 cm (95% CI, -9.7 to -3.8 cm; p < 0.001) for semaglutide. The observed reductions for metformin were -0.8 kg/m2 (95% CI, -1.4 to -0.3 kg/m2; p = 0.001) and -3.4 cm (95% CI, -5.4 to -1.3 cm; p = 0.001). The differences between the two groups were not statistically significant. In both groups, adverse effects were typically mild and transient, predominantly nausea. Furthermore, psychiatric symptoms were reduced, and quality of life improved.

Conclusions: Oral semaglutide represents a viable, effective, and safe treatment option for psychiatric patients. However, further investigation is required to corroborate these findings.