Effect of Canagliflozin Alone and in Combination with Metformin on Ovarian Histology of a Polycystic Ovary Syndrome Rat Model

Background and Objective: Canagliflozin reduces insulin resistance in diabetics and is hypothesized to produce a beneficial effect in polycystic ovarian syndrome (PCOS). Therefore, this study is planned to compare the effects of canagliflozin and metformin alone and in combination on ovarian histology of rat models with letrozole-induced PCOS. Methods: It was a randomized experimental study on Sprague Dawley rats. A total of N = 40 female rats were divided randomly into six groups (A-F). With the exception of normal control group A, rats were given letrozole 1 mg/kg daily for 21 days till PCOS was induced. Group B was disease control, while rats in groups C-F were administered canagliflozin (10 mg/kg), metformin (100 mg/kg), a combination of canagliflozin (10 mg/kg) with metformin (100 mg/kg), and combination of canagliflozin (5 mg/kg) with metformin (50 mg/kg), respectively. Animals were sacrificed on the 48th day. Ovaries and uterus were removed, weighed, and processed for further histopathological analysis. Results: All treatment groups showed significant improvement in ovarian histology. The number of primary and secondary follicles and cystic follicles was significantly lower (p < 0.001) in all treatment groups as compared to the disease control group. Conclusion: Canagliflozin is effective for the treatment of PCOS and augments the effect of metformin in a rat model.