Evaluation of Anti-inflammatory Effects of Metformin and Dapagliflozin in a Complete Freund’s Adjuvant-induced Arthritis Model in Streptozotocin-induced Diabetic Rats

Abstract Context: Chronic inflammation is a hallmark of diabetes mellitus and contributes significantly to its complications. The interplay between hyperglycemia and inflammation forms a vicious cycle that exacerbates disease progression. Recent evidence suggests that drugs such as metformin and sodium-glucose cotransporter-2 inhibitors like dapagliflozin may exert anti-inflammatory effects in addition to glycemic control. Aims: To evaluate the impact of diabetes on chronic inflammation using complete Freund’s adjuvant (CFA)-induced arthritis model in male Wistar rats and to investigate anti-inflammatory effects of metformin, dapagliflozin, and their combination in diabetic rats. Materials and Methods: Diabetes was induced using streptozotocin (40 mg/kg, i.p.), and chronic inflammation was modelled using CFA injection in the right hind paw. Diabetic rats were treated with metformin (180 mg/kg), dapagliflozin (0.9 mg/kg), or their combination for 28 days. Paw edema was measured at defined intervals, and inflammatory changes of ankle joints were analysed by histopathological analysis. Statistical Analysis Used: Data were expressed as mean ± standard error of the mean and analyzed using one-way analysis of variance followed by Tukey’s post hoc test. P ≤ 0.05 was considered statistically significant. Results: Diabetic rats exhibited significantly increased inflammatory parameters as compared to normal controls, while all treatments significantly reduced inflammation, with combination therapy showing efficacy comparable to monotherapy and aspirin. Conclusions: Diabetes exacerbates chronic inflammation in the CFA-induced arthritis model. Metformin and dapagliflozin, individually and in combination, demonstrated anti-inflammatory properties. Their concurrent use may provide a therapeutic benefit in addressing chronic inflammation associated with diabetes.