PCOS: Adding Anti-Inflammatory Drug Roflumilast to Metformin May Reduce Obesity

MedicalResearch.com Interview with:
Mojca Jensterle

Department of Endocrinology. Diabetes and Metabolic Diseases. University Medical Centre. Zaloska 7. Slovenia.

MedicalResearch: What are the main findings of the study?

Answer: This is the first report demonstrating that selective phosphodiesterase enzyme (PDE) 4 inhibitor roflumilast added to metformin (MET) was superior to metformin alone in reducing mean body weight after 12 weeks of treatment in obese women with polycystic ovary syndrome (PCOS), primarily due to a loss of fat mass.

31 women with PCOS diagnosed by the National Institute of Child Health and Human Development criteria aged 33.8 ± 7.4 years with BMI 36.4 ± 5.1 kg/m2concluded the study. They were randomized to MET 1000 mg BID or combined treatment (COM) with MET 1000 mg BID and roflumilast 500 mcg QD. The primary outcome were changes in anthropometric measures of obesity.

At study endpoint subjects treated with COM lost on average 4.2 ± 2.8 kg compared to a 0.9± 2.5 kg weight gain in METgroup (p<0.001). BMI decreased for 1.6 ± 1.1 kg/m2 in COM arm compared to increase for 0.9 ± 2.4 kg/m2 in MET arm (p= 0.001). Total body fat decreased for 0.7±0.4 % in COM as opposed to 0.2 ± 0.1 % increase in MET and visceral adipose tissue (VAT) area as assessed by DXA decreased for 15.5 ± 1.6 cm2 in COM as opposed to 11.4 ± 5.3 cm2 increase in MET. The greater waist circumference reduction was noted in COM (4.2 ± 1 cm) compared with MET (0.8 ± 0.7 cm). The improvements of obesity measures were associated with beneficial effects on fasting glucose levels, insulin resistance and resolution of metabolic syndrome in affected women.

The hypothesis behind the weight decrease and beneficial metabolic impact observed with roflumilast is based on the PDE4 regulation of signaling pathways linked to GLP-1 release. In experimental rodent model a single treatment with roflumilast enhanced plasma GLP-1 levels up to 2.5 -fold.

MedicalResearch: Were any of the findings unexpected?

Answer: When compared to the previously reported effect of roflumilast on body weight in patients with chronic obstructive pulmonary disease and newly diagnosed Type 2 diabetes Mellitus  the mean reduction of body weight in our patients with PCOS that were mainly classified as class II obesity was greater, supporting the correlation between higher BMI and larger weight loss. In addition, metformin in combination with roflumilast may exert its additive beneficial action in part through the additional modulation of the incretin axis by the stimulatory effect of GLP-1.

MedicalResearch: What should clinicians and patients take away from your report?

Answer: Roflumilast added to metformin reduced body weight in obese women with PCOS, primarily due to a loss of fat mass. Our observations are not definitive but do encourage further exploration of the use of this class of medications in metabolic conditions associated with obesity.

MedicalResearch: What recommendations do you have for future research as a result of this study?

Answer: Larger and better designed trials of longer duration are warranted to assess the efficacy and safety of roflumilast in different obese populations.


Phosphodiesterase 4 Inhibition as a Potential New Therapeutic Target in Obese Women with Polycystic Ovary Syndrome
Mojca Jensterle, Tomaz Kocjan, and Andrej Janez
DOI: http://dx.doi.org/10.1210/jc.2014-1430
Received: February 12, 2014 Accepted: May 06, 2014
Published Online: May 13, 2014


Last Updated on November 26, 2014 by Marie Benz MD FAAD