title: Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial.
abstract: 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/m2) 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.
  
  
  BACKGROUND
  The study was retrospectively registered with ClinicalTrials.gov ( NCT02909933 ) on 16thof September 2016.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška 7, Ljubljana, SI-1000, Slovenia.
authors.forename: Mojca
authors.initials: M
authors.lastname: Jensterle
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška 7, Ljubljana, SI-1000, Slovenia.
authors.forename: Nika Aleksandra
authors.initials: NA
authors.lastname: Kravos
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, 1000, Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Goričar
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Zaloška 7, Ljubljana, SI-1000, Slovenia. andrej.janez@kclj.si.
authors.forename: Andrej
authors.initials: A
authors.lastname: Janez
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications* / Q000503:physiopathology; D010865:Pilot Projects; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011379:Prognosis; D011446:Prospective Studies; D055105:Waist Circumference; D015431:Weight Loss
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D008687:Metformin; C517652:hemoglobin A1c protein, human
keywords: Liraglutide; Metformin; Obesity; PCOS