Context: Insulin resistance (IR) and obesity are common features of the polycystic ovary syndrome (PCOS). Weight loss and use of insulin-lowering drugs have been shown to improve both reproductive and metabolic aspects of PCOS.

Objective: We evaluated exenatide and metformin, alone and in combination, on menstrual cyclicity, hormonal parameters, metabolic profiles, and inflammatory markers in overweight, IR women with PCOS.

Design, Setting and Participants: Sixty overweight oligo-ovulatory women with PCOS (BMI >27; 18–40 yr) were randomized to 1 of 3 treatment groups: metformin (MET, 1000 mg BID); exenatide (EX, 10 mcg BID) or combined (COM, metformin 1000 mg BID; exenatide 10 mcg BID) for 24 weeks. The primary outcome was menstrual frequency; secondary outcome measures included changes in ovulation rate, insulin action, anthropometric measures, androgen levels and inflammatory markers.

Results: Forty-two (70%) patients completed the study. COM therapy was superior to EX or MET monotherapy in improving menstrual cyclicity, ovulation rate, free androgen index, and insulin sensitivity measures and reducing weight and abdominal fat. Both exenatide arms were more effective in promoting weight loss than metformin (p=0.003).

Conclusions: Combination appears better than either alone on menstrual cycle frequency and hormonal and metabolic derangements. A marked decrease in central adiposity could partly explain the improvements in reproductive function, insulin-glucose parameters, and adiponectin observed in these overweight women with PCOS treated with COM therapy. Larger trials of longer duration are warranted to assess the long-term efficacy and safety of combined exenatide-metformin therapy in overweight women with PCOS.