Is supplementation of SGLT-2 inhibitor beneficial for obese women with PCOS?

Polycystic ovary syndrome (PCOS) is one of the most prevalent reproductive endocrine disorders affecting about 4–21% of women of reproductive age. The features of the syndrome, as noticed on ultrasonography, are -- ovulatory dysfunction, hyperandrogenism (HA), and polycystic ovaries. Additionally, insulin resistance and obesity are common abnormalities associated with PCOS.

Canagliflozin (CANA) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that could become a novel treatment option for patients with polycystic ovary syndrome (PCOS). Trials focused on the safety and efficacy of SGLT-2 combination therapy in PCOS patients are limited. Considering this, the Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, China, and colleagues aimed to compare the safety and efficacy of metformin (MET) and CANA's combination therapy and metformin monotherapy in metabolic and endocrine profiles of obese and overweight women with PCOS in a randomized controlled trial.

For this purpose, the researchers enrolled fifty-one overweight or obese non-diabetic PCOS women aged 18 and 40. They were randomly assigned to receive either a combination therapy of canagliflozin and metformin or metformin therapy. The CANA/MET group received CANA 100 mg once daily plus MET 1000 mg twice daily; the MET group, however, received MET 1000 mg twice daily for three months. The researchers evaluated changes in anthropometric parameters, menstrual pattern, glucose and lipid homeostasis, gonadal parameters, and adverse events (AEs).

The study led to the following findings:

• Compared with the MET group, women have a significantly lower level of total testosterone (TT), the area under the curve for glucose (AUCGlu), and the area under the curve for insulin (AUCIns) to AUCGlu ratio in the combination group.
• There were no significant differences in menstrual frequency, body mass index, body weight, follicle-stimulating hormone, free androgen index, luteinizing hormone, sex hormone-binding globulin, fasting blood glucose, fasting insulin, androstenedione, AUCIns, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), and APO B/A1 ratio.
• AEs were seen in 57.70% and 68.00% of patients in the CANA/MET and MET groups, respectively.

"CANA and MET combination therapy in overweight and obese women with PCOS may be comparable to MET monotherapy in improving weight control, menstrual frequency, HA, and relieving insulin resistance," the researchers wrote. "However, CANA/MET may be more beneficial in reducing AUCGlu, TT, and AUCIns/AUCGlu ratio within three months."

"Additional trials are required to assess the long-term effects of SGLT-2 inhibitor supplementation in PCOS patients," they concluded.

Reference:

Zhang J, Xing C, Cheng X and He B (2022) Canagliflozin combined with metformin versus metformin monotherapy for endocrine and metabolic profiles in overweight and obese women with polycystic ovary syndrome: A single-center, open-labeled prospective randomized controlled trial. Front. Endocrinol. 13:1003238. doi: 10.3389/fendo.2022.1003238