The effects of 8 months of metformin on circulating GGT and ALT levels in obese women with polycystic ovarian syndrome

Summary Context:  The prevalence of non‐alcoholic fatty liver disease (NAFLD) in polycystic ovarian syndrome (PCOS) is high. Small studies have shown reductions in serum alanine aminotransaminase (ALT) and γ‐glutamyltransaminase (GGT) concentrations, both surrogate liver fat markers, and sometimes improvements in liver histology in individuals with NAFLD treated with metformin. Aims:  We investigated whether metformin reduces serum ALT and GGT concentrations in obese women with PCOS. Methods:  We performed post hoc data analysis from a trial, involving 82 obese women aged 22–46 years with PCOS, conducted at an academic institution. Participants were treated with metformin 1500 or 2550 mg/day for 8 months. Anthropometric measurements and blood samples (serum ALT, GGT, lipids, leptin, C‐reactive protein, insulin, glucose analyses) were taken at baseline, 4 and 8 months. Results:  Sixty‐six participants completed the study. Mean weight, serum ALT and GGT decreased from 100.3 to 96.6 kg (p < 0.0001), 29.7 to 25.8 U/l (p = 0.012) and 21.4 to 16.9 U/l (p < 0.0001) respectively. Associations between weight reduction and decreases in serum ALT and GGT were highly significant and independent of change in Homeostasis Model Assessment of Insulin Resistance. In women with baseline ALT > 29.7 U/l (median), ALT reduction was highly significant (p = 0.005); however in those with baseline ALT < 29.7 U/l, ALT did not change despite similar weight reduction. There was no difference in reductions in ALT and GGT when the two metformin doses were compared. Intention‐to‐treat analyses gave comparable results. Conclusions:  Metformin therapy is associated with reductions in surrogate liver fat markers in obese women with PCOS. This adds indirect support for a benefit of metformin in attenuating/reversing liver fat accumulation in PCOS and more generally.