Metformin increases fasting plasma peptide tyrosine tyrosine (PYY) in women with polycystic ovarian syndrome (PCOS)

OBJECTIVE: The beneficial effects of metformin in patients with type 2 diabetes mellitus (T2DM) and polycystic ovarian syndrome (PCOS) are thought to be in part due to weight reduction. However, the mechanisms by which metformin causes weight loss are unclear. We sought to determine whether circulating levels of the anorectic gut hormone peptide tyrosine tyrosine (PYY) show any correlation with metformin-induced weight loss. DESIGN AND PATIENTS: We examined the acute effects of orally administrated metformin on fasting PYY levels in eight healthy normal-weight female subjects. Subsequently, we evaluated the effects of 6 months metformin treatment on fasting PYY levels and anthropometric measurements in 20 women with PCOS. RESULTS: In normal-weight females 10 days' metformin treatment increased fasting PYY levels (P < 0.01). Similarly, in PCOS subjects metformin treatment increased fasting PYY concentrations (P < 0.05). In both groups a marked variation in PYY increase in response to metformin was observed. Long-term metformin treatment was associated with improvements in weight (P < 0.05), BMI (P < 0.05), fasting glucose (P < 0.05) and menstrual frequency (P < 0.01). Interestingly, change in PYY levels were correlated with change in waist circumference (r = 0.55, P < 0.05). CONCLUSIONS: Acute and chronic oral metformin administration increase fasting PYY levels and may contribute to metformin's weight loss effect. Further studies are now required to clarify whether changes in circulating PYY levels in response to metformin treatment can be used to predict which patients will subsequently lose weight long-term and gain cycle restoration.