Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin

Objective: The effect of metformin on weight reduction in polycystic ovary syndrome (PCOS) is often unsatisfactory. In this study, we investigated the potential add-on effect of treatment with the glucagon-like peptide-1 receptor agonist liraglutide on weight loss in obese nondiabetic women with PCOS who had lost < 5% body weight during pretreatment with metformin. Methods: A total of 40 obese women with PCOS, who had been pretreated with metformin for at least 6 months, participated in a 12-week open-label, prospective study. They were randomized to one of three treatment arms: metformin (MET) arm 1000 mg BID, liraglutide (LIRA) arm 1.2 mg QD s. c., or combined MET 1000 mg BID and LIRA (COMBI) 1.2 mg QD s. c. Lifestyle intervention was not actively promoted. The primary outcome was change in body weight. Results: Thirty six patients (aged 31.3 +/- 7.1 years, BMI 37.1 +/- 4.6 kg/m(2)) completed the study: 14 on MET, 11 on LIRA, and 11 on combined treatment. COMBI therapy was superior to LIRA and MET monotherapy in reducing weight, BMI, and waist circumference. Subjects treated with COMBI lost on average 6.5 +/- 2.8 kg compared with a 3.8 +/- 3.7 kg loss in the LIRA group and a 1.2 +/- 1.4 kg loss in the MET group (P < 0.001). The extent of weight loss was stratified: a total of 38% of subjects were high responders who lost >= 5% body weight, 22% of them in the COMBI arm compared with 16 and 0% in the LIRA and MET arm respectively. BMI decreased by 2.4 +/- 1.0 in the COMBI arm compared with 1.3G1.3 in LIRA and 0.5 +/- 0.5 in the MET arm (P < 0.001). Waist circumference also decreased by 5.5 +/- 3.8 cm in the COMBI arm compared with 3.2 +/- 2.9 cm in LIRA and 1.6 +/- 2.9 cm in the MET arm (P=0.029). Subjects treated with liraglutide experienced more nausea than those treated with metformin, but severity of nausea decreased over time and did not correlate with weight loss. Conclusions: Short-term combined treatment with liraglutide and metformin was associated with significant weight loss and decrease in waist circumference in obese women with PCOS who had previously been poor responders regarding weight reduction on metformin monotherapy.