Dual Assessment of Antidiabetic Efficacy and Adverse Outcomes of Semaglutide and Tirzepatide in Type 2 Diabetic Swiss Albino Male Mice

Alzahrani, Elham; Aldhmash, Badr; Elnagar, Doaa M; Batis, Mohamed; Almutairi, Mukhallad; Alqarni, Aisha H; Alqahtani, Wajdan S; Almansour, Mansour; Rady, Ahmed; Khan, Amjad; Ateya, Ahmed

doi:10.21608/ejvs.2025.434679.3213

Dual Assessment of Antidiabetic Efficacy and Adverse Outcomes of Semaglutide and Tirzepatide in Type 2 Diabetic Swiss Albino Male Mice

Document Type : Original Article

Authors

¹ 1 Zoology department, college of Science, King Saud University ,Riyadh, Saudi Arabia

² 2 Family and community medicine department, college of medicine, King Saud University ,Riyadh, Saudi Arabia

³ 3 Kangbuk Samsung Hospital, Samsung Medical Centre, School of Medicine, Sungkyunkwan University (SKKU), Seoul, Korea

⁴ Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.

10.21608/ejvs.2025.434679.3213

Abstract

Semaglutide (S) is a GLP-1 receptor agonist; Tirzepatide (T) has dual GLP-1/GIP receptor agonism. This research compared their therapeutic effects and adverse reactions in a type 2 diabetes mellitus (T2DM) mouse model. Body weight, blood glucose, lipid profile, insulin, and IGF1 were estimated, as well as histopathological examination and gene expression. S and T independently led to prominent body weight reduction in diabetic mice, as well as enhancements of glucose and lipid profiles. However, histological examination showed that pancreas hemorrhage and intestine ulceration appeared after treatment. Immunohistochemistry and RT-PCR analysis revealed that insulin and glucagon expression were partially restored, CYP2E1 was over-expressed at a lower level after therapy. In conclusion, Semaglutide and Tirzepatide showed similar metabolic advantages; however, they caused significant changes in intestine and pancreatic structure, emphasizing the necessity for careful assessment over the long term.

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