Supplementary Material for: Effect of Dual GLP-1/GIP Receptor Agonist (Tirzepatide) Versus Bariatric Surgery on Weight Loss and NAFLD

Objectives: Bariatric surgery is a well-established treatment for obesity and type 2 diabetes. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has emerged as a promising therapy for type 2 diabetes. This study aimed to compare the effects of bariatric surgery, semaglutide (a GLP-1 receptor agonist), and tirzepatide in Sprague-Dawley rats fed a high-fat diet. Methods: Rats were divided into surgery, semaglutide, and tirzepatide treatment groups, along with a control group (sham). Weight, oral glucose tolerance, and levels of metabolic markers were assessed, along with adipose and liver tissue analysis. Results: Surgery led to a 15.5% weight reduction, while rats treated with semaglutide exhibited a 10.7% reduction. Tirzepatide treatment at various concentrations (10, 50, and 100 nmol/kg) resulted in weight reductions of 5.0%, 14.9%, and 17.7% respectively, compared to the sham group. Metabolic analyte levels decreased in intervention groups compared to the sham group, indicating improved metabolic health and glucose tolerance. Adipose tissue weight and hepatic liver fat droplets decreased in the intervention groups. Conclusion: Bariatric surgery and tirzepatide treatment significantly improved metabolic parameters in obese rats. Tirzepatide, particularly at higher concentrations, showed pronounced improvements compared to surgery and semaglutide. These findings suggest that high doses of tirzepatide could be explored as an alternative to bariatric surgery for the treatment of obesity.