Adding the phosphodiesterase type 4 inhibitor roflumilast (Daliresp) to metformin therapy helps women with polycystic ovary syndrome (PCOS) lose extra pounds and improve some metabolic markers.

In a prospective, open-label, randomized trial, patients who received the combination of metformin and roflumilast performed better than women who were given metformin alone.

This was announced by Dr. Mojca Jensterle from the University Medical Center Ljubljana at a joint meeting of the Society of Endocrinology and the International Congress of Endocrinology (ICE / ENDO) in Chicago.

The results of the study were published in the online Journal of Clinical Endocrinology and Metabolism..

Phosphodiesterase type 4 (PDE-4) is very active in the ovaries, where it plays an important role in the processes of egg maturation and ovulation.. Inhibition of PDE-4 is of some importance in the regulation of metabolism, having a positive effect on glucose balance and weight control..

Since these factors are involved in the development of PCOS, the researchers decided to test the effectiveness of roflumilast in women with hormonal and metabolic disorders in this disease.. They included 36 women aged 34 with an average body mass index of 36.4 kg/m2.. The study lasted 12 weeks..

All women were treated with metformin prior to this work and were divided into two groups at the start of the study.. One continued to take metformin 1000 mg twice a day, and the second received additional roflumilast 500 mcg once a day.

Primary outcome changed in terms of anthropometric parameters of obesity, secondary - in terms of hormonal and metabolic changes. Of the 31 women who reached the endpoint of the study, 16 were on metformin, 15 were on combination therapy..

Patients in the combination therapy group lost more weight with an average of 4.2 kg (9 lbs).

Women in the metformin-only group lost only 0.9 kg (2 lb), P\u003c0.001.

Accordingly, in the combination therapy group there was a more noticeable loss of BMI - an average of 1.6 kg/m2 versus 0.9 kg/m2 in the metformin group, P \u003d 0.001.

Women who received the combination of metformin and roflumilast showed a significant reduction in visceral adipose tissue (VAT), while patients on metformin even gained VAT (P \u003d 0.02).

Dr. Jensterle and colleagues note that the combined therapy achieved a reduction in aldosterone (P \u003d 0.013), free testosterone (P \u003d 0.002), and HOMA-IR insulin resistance score (P \u003d 0.027). Along with these positive changes, there is a significant increase in the level of sex hormone-binding globulin (P\u003d0.024).

Concluding that the combination of roflumilast and metformin may help women with PCOS lose weight, Dr. Jensterle called for further research into roflumilast, not only in PCOS, but also in metabolic diseases leading to obesity..

Dr. Bulent Okan Yildiz from Hacettepe University School of Medicine (Ankara, Turkey), who moderated the presentation of this study, pointed out that this study did not have sufficiently reliable controls, and its results on the effectiveness of PDE-4 inhibitors in PCOS cannot be.

" If you are comparing 2 drugs, then you cannot accept into the study a group that has been on one of these drugs (metformin) for 2 years. This is an incorrect comparison,” Yildiz told US MedPage Today..

He also says that the changes in body weight were unexpected, especially the gain in visceral adipose tissue in the metformin group: “The patients were on metformin for an average of 2 years, but in the 3 months of the study, they added VAT? It's pretty unexpected. I'm surprised by the results."

medbe. en.