Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial

Background: Liraglutide 3 mg was recently approved as an anti-obesity drug. Metformin is weight neutral, yet it could enhance the therapeutic index of GLP-1 agonist. We compared weight-lowering potential of liraglutide 1. 2 mg in combination with metformin to liraglutide 3 mg monotherapy in obese PCOS. Methods: Thirty obese women with PCOS (aged 33.1 +/- 6.1 years, BMI 38.3 +/- 5.4 kg/m(2)) were randomized to combination (COMBO) of metformin (MET) 1000 mg BID and liraglutide 1.2 mg QD (N= 15) or liraglutide 3 mg (LIRA3) QD alone (N= 15) for 12 weeks. The primary outcome was change in anthropometric measures of obesity. Results: Both treatments led to significant weight loss (-3.6 +/- 2.5 kg, p = 0.002 in COMBO vs -6.3 +/- 3.7 kg, p = 0.001 in LIRA3). BMI and waist circumference reduction in LIRA3 was greater than in COMBO (-2.2 +/- 1.3 vs -1.3 +/- 0.9 kg/ m2, p = 0.05 and -4.2 +/- 3.4 vs -2.2 +/- 6.2 cm, p = 0.014, respectively). Both interventions resulted in a significant decrease of post-OGTT glucose levels. COMBO significantly reduced total testosterone and was associated with less nausea. Conclusions: Short-term interventions with COMBO and LIRA3 both led to significant improvement of measures of obesity in obese PCOS, LIRA3 being superior to COMBO. However, COMBO further improved androgen profile beyond weight reduction and was associated with better tolerability.