Efficacy of Semaglutide as Adjuvant Treatment for Sleeve Gastrectomy: A Proof‐of‐Concept Study in Mice

Objective This proof‐of‐concept study evaluated the impact of adding semaglutide as an adjuvant therapy to sleeve gastrectomy (SG) on weight loss and metabolic outcomes in obese mice. Methods C57Bl6/J male received for 12 weeks high‐fat diet and 20% fructose‐enriched water, then they were randomized to undergo SG or a Sham surgery and were subsequently treated with either semaglutide or a vehicle for 8 weeks. Mice were weighed weekly, and food intake, plasma glucose levels, and adipose tissue weights were measured. Results Both SG and semaglutide alone significantly reduced body weight compared with Sham surgery (−22.9%, p = 0.049 and −28.2%, p = 0.003, respectively). SG and semaglutide combination resulted in the greatest reduction (−30.0%, p = 0.003). Food intake was only significantly decreased in the semaglutide group. Although SG has no significant effect, semaglutide alone and in association with SG significantly decreased the plasma glucose concentration. The combination also led to a significant reduction in plasma cholesterol levels (−37.5% ± 4.8% vs. 5.6% ± 6.8%, p = 0.023). Liver steatosis was reduced in all treated groups. Conclusions Adding semaglutide to SG potentiates weight loss and metabolic benefits of surgery in obese mice, but no more than with semaglutide alone. These findings support further investigation of combined surgical and pharmacological approaches in obesity treatment.