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CHICAGO -- Adding the phosphodiesterase-4 (PDE4) inhibitor roflumilast (Daliresp) to metformin may help obese women with polycystic ovarian syndrome (PCOS) shed pounds and improve other metabolic markers, researchers reported.
In a randomized, prospective, open-label study, patients on the combination therapy lost significantly more weight than those taking metformin alone, Mojca Jensterle, MD, of University Medical Center Ljubljana in Slovenia, and colleagues reported at the joint meeting of the Endocrine Society and the International Congress on Endocrinology (ICE/ENDO) here.
The study was also published .
PDE4 is highly expressed in human ovaries and has been shown to play a role in oocyte maturation and ovulation. Inhibition of PDE4 has also been shown to play a role in the regulation of metabolism, with beneficial effects on glucose homeostasis and weight reduction.
Because these factors are involved in PCOS, the researchers investigated if the PDE4 inhibitor roflumilast could impact body weight as well as hormonal and metabolic status in obese women with the disease. They assessed 36 women -- mean age 34, mean body mass index (BMI) 36.4 kg/m2 -- in a 12-week study.
All of the women had been pretreated with metformin, and were randomized to either continue on metformin 1,000 mg twice a day alone, or in combination with roflumilast 500 mcg once daily.
The primary outcome was change in anthropometric measures of obesity, with secondary outcomes of hormonal and metabolic changes.
A total of 31 women completed the study, 16 in the metformin group and 15 in the combination arm.
Patients in the combination group lost more weight -- an average of 4.2 kg (9 lbs) -- while those on metformin alone gained an average of 0.9 kg or 2 lbs (P<0.001).
The combination therapy arm also had a greater reduction in BMI, with a decline of 1.6 kg/m2 compared with an increase of 0.9 kg/m2 for those on metformin alone (P=0.001).
Women on the combination also had a reduction in visceral adipose tissue (VAT), while those on metformin gained VAT, the authors reported (P=0.02).
Jensterle and colleagues also noted reductions in androstenedione (P=0.013), free testosterone (P=0.002) and homeostatic model assessment insulin resistance (HOMA-IR) score (P=0.027), along with a significant increase in sex hormone binding globulin (P=0.024) for those on metformin and roflumilast.
Concluding that roflumilast plus metformin may help lower body weight in women with PCOS, Jensterle called for further study of PDE4 inhibitors not only in PCOS but in other metabolic conditions associated with obesity.
, of Hacettepe University School of Medicine in Ankara, Turkey, who moderated the session during which the findings were presented, cautioned that the study did not have a proper control so it would be hard to draw conclusions solely about the effects of PDE4 inhibitors in PCOS.
"There are lots of limitations," Yildiz told ľֱ. "If you compare two drugs, you can't take one group that's been on the one drug for more than 2 years," he said, referring to the patients' history on metformin. "It's not a fair comparison."
He also said it was unexpected to see the changes in body weight, particularly the gain in the metformin group.
"They were on metformin for 2 years, but in 3 months they put on weight?" he said. "That's quite unexpected. I am quite surprised by these results."
Disclosures
Jensterle disclosed no relevant relationships with industry.
Primary Source
Endocrine Society and the International Congress on Endocrinology
Source Reference: Jensterle M, et al. "Phosphodiesterase 4 inhibition as a potential new therapeutic target in obese women with polycystic ovarian syndrome" ICE/ENDO 2014;Abstract OR04-5.