Effect of Ticagrelor on Glycaemic Parameters and Inflammatory Mediators in High Fat Diet and Streptozotocin Induced Diabetic Rats: An Experimental Study

Introduction: Type 2 Diabetes Mellitus (T2DM) is a growing global health concern, often associated with chronic inflammation and cardiovascular complications such as Acute Coronary Syndrome (ACS). Emerging evidence suggests that antiplatelet agents may exert beneficial effects beyond their cardiovascular indications, including the modulation of glycaemic control and inflammatory responses. Ticagrelor, a P2Y12 receptor antagonist primarily used for managing ACS, has been proposed to influence metabolic and inflammatory pathways. Aim: To evaluate the effect of ticagrelor on glycaemic parameters in a High Fat Diet (HFD) and Streptozotocin (STZ)-induced diabetes mellitus in male Wistar rats. Materials and Methods: The present experimental study was conducted in the Department of Pharmacology at Jawaharlal Nehru Medical College, Belagavi, Karnataka, India, from March 2021 to February 2022. A total of 36 rats were utilised in the study. Among these, six were designated as the normal control group. The remaining 30 rats were subjected to diabetes induction through a combination of HFD administration for two weeks and a single intraperitoneal injection of STZ at a dose of 35 mg/kg. Following the induction of diabetes, one group served as the diabetic control with no treatment, while other groups received oral treatment either with metformin, ticagrelor (16.2 mg/kg), or ticagrelor (35 mg/kg) for six weeks. Body weights and Fasting Blood Glucose (FBG) levels were measured at baseline, 14 days of HFD, three weeks following treatment, and at the end of the study. Glycated Haemoglobin A1c (HbA1c) was measured at baseline and at the end of the study. Inflammatory markers Interleukin (IL)-1β, Tumour Necrosis Factor (TNF)-α, and IL-6 were assessed at the end of the study. Data were presented as Mean±Standard Error of the Mean (SEM). A p-value ≤0.05 was considered statistically significant. One-way Analysis of Variance (ANOVA) followed by Bonferroni’s post hoc test was used for the analysis of study variables, and paired data were analysed using the paired t-test. Results: All three treatments significantly reduced FBG (p<0.0001) and HbA1c (p<0.0001) compared to the untreated rats. Additionally, compared to the ticagrelor (16.2 mg/kg) group, the ticagrelor (35 mg/kg) group significantly decreased these values (p<0.0001). The inflammatory markers (IL-1β, IL-6, TNF-α) were significantly reduced (p<0.0001) in all treatment groups compared to untreated rats. Conclusion: The treatment of diabetic rats with oral ticagrelor improved the HFD and STZ-induced elevations in Fasting Blood Sugar (FBS), glycosylated hemoglobin (HbA1c), and inflammatory mediators. Furthermore, ticagrelor (35 mg/kg) was found to be more efficacious across all trial variables compared to Ticagrelor (16.2 mg/kg).