Combination of Metformin and Epigallocatechin-3Gallate Lowers Cortisol, 11β-Hydroxysteroid Dehydrogenase Type 1, and Blood Glucose Levels in Sprague Dawley Rats with Obesity and Diabetes

Background: The combined effects of metformin and epigallocatechin-3-gallate (EGCG) on cortisol, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), and blood glucose levels have not been investigated. This study evaluated the effectiveness of combining EGCG with metformin in regulating those levels in a rat model of diet-induced diabetes and obesity. Methods: Thirty diabetic and obese rats on a high-fat diet were treated daily for 28 days with EGCG (100 mg/kg of body weight/day), metformin (200 mg/kg of body weight/day), or both. Control groups comprised lean rats, untreated obese diabetic rats, and metformin-only-treated rats. Blood samples were collected to measure cortisol and fasting blood glucose (FBG) levels and liver tissue samples were examined for 11β-HSD1 levels. Results: Rats receiving combination therapy had significantly reduced cortisol levels (from 36.70±15.13 to 31.25±7.10 ng/mL) compared with the untreated obese diabetic rats but not the rats receiving monotherapy. Rats receiving combination therapy and EGCG monotherapy had significantly lower 11β-HSD1 levels compared with the untreated obese diabetic rats (92.68±10.82 and 93.74±18.11 ng/L vs. 120.66±14.00 ng/L). Combination therapy and metformin monotherapy significantly reduced FBG levels (440.83±133.39 to 140.50±7.36 mg/dL and 480.67±86.32 to 214.17±102.78 mg/dL, respectively) by approximately 68.1% and 55.4% compared with rats receiving EGCG monotherapy and untreated obese diabetic rats. Conclusion: Combining EGCG with metformin exhibited synergistic effects compared with monotherapy for managing diabetes, leading to improved outcomes in reduction of baseline cortisol levels along with reduction in 11β-HSD1 and blood glucose levels.