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

Sep 3, 2025Obesity (Silver Spring, Md.)

Semaglutide’s effectiveness as an additional treatment after stomach surgery in mice

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Abstract

The combination of sleeve gastrectomy and semaglutide resulted in a 30.0% reduction in body weight in obese mice.

Both sleeve gastrectomy and semaglutide alone led to significant weight loss compared to sham surgery, with reductions of 22.9% and 28.2%, respectively.
The addition of semaglutide to sleeve gastrectomy produced the greatest weight loss effect.
Food intake significantly decreased only in the semaglutide group.
Semaglutide alone and in combination with sleeve gastrectomy significantly lowered plasma glucose concentrations.
The combination therapy also resulted in a significant reduction in plasma cholesterol levels by 37.5%.

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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.

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

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