Toxicity of Semaglutide upon sub chronic administration in Rabbits

Semaglutide is an anti-obesity and anti-diabetic drug used in long-term weight management and for the treatment of type 2 diabetes. A toxicology study was conducted on a generic synthetic version of Semaglutide Injection (2 mg/3 mL) produced by Biocon Pharma, using New Zealand White Rabbits. In this study, Rabbits (4/sex/group) were administered subcutaneously, once weekly, with Semaglutide Injection at dose levels of 0.062, 0.124, and 0.248 mg/kg for a period of 90 days. Across all dose groups, treatment-related significant decreases in food consumption, weight loss, fewer fecal pellets, limited urine pools, and decreased activity were observed. These reported changes are known class effects of GLP-1 receptor agonists. Additionally, all changes noted in hematology, clinical, and anatomic pathology parameters were linked to reduced food intake and weight loss. Results showed one mortality each in treatment groups with Semaglutide administered at 0.124 mg/kg (mid dose) and 0.248 mg/kg (high dose). Mortality was related to the exaggerated pharmacological effect on body weight and feed consumption. Based on the findings from this study, the No-Observed-Adverse-Effect-Level (NOAEL) for Semaglutide Injection 2 mg/3 mL (0.67 mg/mL) was found to be 0.062 mg/kg in New Zealand White Rabbits.