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

Abstract

ObjectiveThe 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.MethodsA 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.ResultsThirty six patients (aged 31.3±7.1 years, BMI 37.1±4.6 kg/m2) 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 1.3±1.3 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.ConclusionsShort-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.

Genetic variability in GLP-1 receptor is associated with inter-individual differences in weight lowering potential of liraglutide in obese women with PCOS: a pilot study

“…Eleven patients from the present cohort had previously participated in our pilot randomized study conducted with 36 obese PCOS women demonstrating that 12-week combined treatment with liraglutide 1.2 mg QD s.c. alone or in combination with metformin was associated with significant weight loss in obese women with PCOS who had been previously poor responders regarding weight reduction with lifestyle intervention and metformin. Women lost on average 3.8 kg on liraglutide alone and 6.5 kg when liraglutide was combined to metformin [11].…”

“…Some of them have previously participated in the randomized clinical trials [10,11] at the Outpatient Clinics of Department of Endocrinology, Diabetes and Metabolic Diseases at the University Medical Centre Ljubljana from November 2011 to December 2014. All the patients were assigned to liraglutide at a dose of 0.6 mg injected s.c. once per day and increased to 1.2 mg/day after 1 for 12 weeks.…”

“…Only three randomized studies have addressed their possible use in PCOS [8][9][10]. We have previously shown that obese women with PCOS who had not responded to lifestyle intervention and metformin treatment might benefit from short-term intervention with long-acting GLP-1RA liraglutide as an add-on therapy to metformin regarding weight loss [11]. Another study of obese PCOS women provided evidence that combined treatment with short-acting GLP-1RAs exenatide and metformin was superior to exenatide and metformin monotherapies in improving their weight loss [8].…”

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

“…Menstrual cycle frequency, the primary study endpoint, as well as ovulatory rates, hormonal parameters and metabolic markers were significantly improved in all treatment groups and to a significantly greater degree in the group taking the combined treatment, compared with the metformin-treated group (232). Another preliminary report has suggested that another GLP1 analogue, liraglutide, may have an add-on effect on weight loss in obese women with PCOS who had lost !5% body weight during a 6-month pre-treatment with metformin (233).…”

Successful Pregnancy after Improving Insulin Resistance with the Glucagon-Like Peptide-1 Analogue in a Woman with Polycystic Ovary Syndrome: A Case Report and Review of the Literature

“…Their outcome [11] was combined treatment with EX, and metformin for 24-week was superior to EX and metformin monotherapies in improving menstrual cyclicity, ovulation rate, androgens, insulin sensitivity measures, and reducing weight and abdominal fat. Similarly, the long-acting GLP1 analog, liraglutide, has been shown to cause significant weight loss in women with PCOS, when prescribed as monotherapy or in combination with metformin in a 12-week observational study [12]. Liu et al [13] propose that GLP-1 might be useful in alleviating β-cell stress and might improve β-cell functions and survival.…”