Evaluation of Anti-diabetic Activity of Vonoprazan and its Synergistic Effect with Metformin in Streptozotocin Induced Diabetes in Rats.

Background: Vonoprazan, classified as a potassium-competitive acid blocker, suppresses the secretion of gastric acid and indirectly increases circulating gastrin levels through a feedback mediated mechanism. Recent findings indicate that vonoprazan may influence glucose homeostasis and insulin sensitivity, suggesting a possible role in the modulation of metabolic aberrations, specifically pertaining to the pathophysiology of Type 2 Diabetes Mellitus (T2DM). Objectives: The current study was conducted to appraise the anti-diabetic properties of vonoprazan and to assess its combined effect with metformin in a rat model of T2DM established via a high-fat diet (HFD) combined with streptozotocin (STZ). Methods: Twenty-five adult male rats were participants randomly assigned to five experimental groups (n=5): normal control, positive control, diabetic rats administered metformin, diabetic rats administered vonoprazan, and diabetic rats subjected to a dual regimen comprising vonoprazan and metformin. After inducing diabetes, the treatments were delivered via oral gavage once daily for four weeks. At the experimental endpoint, blood samples were processed for biochemical assessment. Pancreatic tissues were excised, weighed, and processed for histological evaluation to investigate morphological alteration. Results: Administration of vonoprazan, metformin, or their combination significantly improved glycemic indices, as evidenced by reduction in fasting blood glucose (FBG) and insulin resistance. Additionally, treated groups exhibited significant decreases in body weight and dyslipidemic markers, including low-density lipoprotein (LDL), total cholesterol (TC), and triglyceride (TG). Conversely, serum insulin concentrations, high-density lipoprotein (HDL) levels, absolute pancreatic mass, and pancreas-to-body weight ratio were significantly elevated compared with the positive control. The combined vonoprazan with metformin regimen demonstrated superior metabolic and histological improvement relative to monotherapy. Conclusion: These findings indicate that vonoprazan possesses notable metabolic benefits and potentiates the therapeutic effects of metformin. Therefore, vonoprazan may serve as an emerging ancillary agent in the therapeutic landscape of T2DM, providing a novel pharmacological approach for enhancing glycemic and lipid profile outcomes.