Synergistic Effects and Molecular Mechanism of Metformin and Vildagliptin in experimental Prediabetes

Abstract: Background: Prediabetes, a transitional state preceding type 2 diabetes, is linked to heightenedrisks of cardiovascular events and stroke. While insulin resistance is well established as aprimary feature, recent insights emphasize the involvement of beta cell dysfunction inPrediabetes. Objective: This study explores the combined therapeutic impact of Metformin and the DPP4inhibitor: Vildagliptin in addressing both insulin resistance and beta cell regeneration in a ratmodel of prediabetes and elucidates the molecular mode of action.Methods: Adult male rats were subjected to a high-fat diet followed by a high-fat, high-sugarliquid regimen to induce Prediabetic conditions. Subsequent assessments included biochemicalparameters, histopathological studies.Results: The combination therapy of Metformin and Vildagliptin resulted in better glycemiccontrol than Metformin& Vildagliptin alone.Conclusion: Co-administration of Metformin and Vildagliptin offers a dual-targeted approachby improving both insulin sensitivity and beta cell function, showing enhanced therapeuticpotential over Metformin monotherapy for Prediabetes management.