Short Term Monotherapy with GLP-1 Receptor Agonist Liraglutide or PDE 4 Inhibitor Roflumilast Is Superior to Metformin in Weight Loss in Obese PCOS Women: A Pilot Randomized Study

Presentation Number: OR15-4
Date of Presentation: March 6th, 2015

Mojca Jensterle*1, Vesna Salamun2, Tomaz Kocjan3, Eda Vrtacnik Bokal2 and Andrej Janez4
1University Medical Centre Ljubljana, Ljublijana, Slovenia, 2University Medical Centre Ljubljana, 3University Medical Centre Ljubljana, Ljubljana, Slovenia, 4University Medical Center Ljubljana, Ljubljana, Slovenia


Context: Weight management by lifestyle intervention and metformin often remains unsatisfactory in obese women with polycystic ovary syndrome (PCOS). New treatment options for weight reduction acting through glucagon-like peptide (GLP)-1 mediated effects could be considered in these patients.

GLP-1 receptor agonist liraglutide is now FDA approved anti- obesity agent, yet the experiences with its use in PCOS related obesity are still very limited. Phosphodiesterase enzymes (PDE) 4 inhibitor roflumilast is well recognized as efficient anti-inflammatory drug. However, its less known beneficial metabolic action based on the interplay between the inhibition of PDE4 and the regulation of GLP-1 release has never been directly compared to GLP-1 receptor agonist, either in PCOS or in any other obese population, yet. In addition, the expression of PDE4 enzymes in ovaries and the recognised involvement of PDEs in steroidogenesis do not exclude a potential role of roflumilast in direct regulation of ovarian steroidogenesis and in the pathophysiology of PCOS.

Objective: To compare the effects of liraglutide, roflumilast and metformin on body weight reduction, glucose homeostasis, androgen profile and menstrual frequencies in obese women with PCOS.

Design/Main Outcome Measure: A 12-week prospective randomized open-label study was conducted with 45 obese PCOS diagnosed by the ASRM-ESHRE Rotterdam criteria. They were randomized to metformin (MET) 1000 mg BID or liraglutide (LIRA) 1.2 mg QD s.c. or roflumilast (ROF) 500 mcg QD. The primary outcome was change in measures of obesity.

Results: 41 patients (aged 30.7 ± 7.9 years, BMI 38.6 ± 6.0 kg/m2, mean ± SD) completed the study. Subjects treated with LIRA lost on average 3.1±3.5 kg (p= 0.006), on ROF 2.1±2.0 kg (p= 0.002) vs 0.2±1.83 kg in MET group. BMI decreased for 1.1±1.26 kg/m2 in LIRA (p= 0.006), for 0.8±0.99 kg/m2 in ROF (p= 0.001) vs 0.1±0.67 kg/m2 in MET. LIRA was superior to MET in reducing weight (p= 0.022), BMI (p= 0.020) and waist circumference (p=0.007). LIRA also resulted in decrease in VAT area (p=0.015) and more favorable glucose homeostasis during OGTT. ROF resulted in reduction of waist circumference (p=0.023). In addition, ROF led to testosterone reduction (p=0.05) and increase in menstrual frequencies (p=0.009) when compared to baseline.

Conclusion: Short-term monotherapy with liraglutide or roflumilast was associated with significant weight loss in obese PCOS, liraglutide being superior to roflumilast. Reduction of body weight with liraglutide resulted in improvement of body composition. Despite the superiority of liraglutide in weight reduction and glucose homeostasis, roflumilast resulted in testosterone reduction and increase in menstrual frequencies not being demonstrated in liraglutide arm. Metformin did not significantly affect the body weight or other observed outcomes in this short-term period yet.


Nothing to Disclose: MJ, VS, TK, EV, AJ