Antidiabetic Effects of Gymnema sylvestre and Metformin Co-Therapy in a Type 2 Diabetic Rat Model

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and hyperglycemia. Metformin is the standard therapy, however plant-based adjuncts such as Gymnema sylvestre (GS) are gaining interest for their anti-diabetic potential. Objectives: To evaluate the anti-diabetic effects of GS, alone and with metformin, on glycemic control, lipid profile, renal function, and body weight in high-fat diet and streptozotocin (STZ)-induced T2DM rats. Methods: Thirty male Sprague Dawley rats (150 ± 20 g) were divided into five groups: normal control, diabetic control (DC), metformin-treated (Met), GS-treated, and combination-treated (Met + GS). T2DM was induced by 21 days of high-fat diet followed by two STZ injections (25 mg/kg, five days apart). Rats with fasting blood glucose (FBG) ≥270 mg/dL were treated for 28 days. Biochemical parameters (FBG, HbA1c, serum creatinine, and cholesterol) and body weight were assessed. Results: By Day 28, all treatment groups showed significant improvements compared to DC (p < 0.05). Metformin produced the greatest reductions in FBG, cholesterol, creatinine, and HbA1c. GS monotherapy had modest but significant effects, while Met + GS improved glycemic control and lipid profile more effectively than GS alone. Metformin remained superior in renal protection. All treated groups showed significantly higher body weights than DC, indicating protection against STZ-induced weight loss. Conclusion: This study demonstrated that Metformin and GS, individually and in combination, improved glycemic control and metabolic outcomes in T2DM rats. While metformin showed the greater efficacy, combination therapy provided additive benefits, supporting GS as a potential adjunct in T2DM management.