Glucagon-like peptide-1 analogue, liraglutide, improves liver fibrosis markers in obese women with polycystic ovary syndrome and nonalcoholic fatty liver disease

Abstract

Introduction: Nonalcoholic fatty liver disease (NAFLD) has been linked to polycystic ovary syndrome (PCOS) and carries an increased risk of liver cirrhosis. Procollagen type 3 amino-terminal peptide (PIIINP) is an independent predictor of liver cirrhosis.

Objective: To assess whether 6-month treatment with GLP-1 analogue, liraglutide, improves markers of liver fibrosis.

Design: A case-control study comparing women with PCOS to age- and weight-matched controls. PCOS was diagnosed according to the Rotterdam criteria. All participants underwent liver function tests and liver ultrasound scan to assess for fatty infiltration. Serum marker for liver fibrosis, PIIINP, was measured at baseline and after 6-month treatment with liraglutide 1·8 mg od.

Results: Nineteen women with PCOS and 17 controls were recruited, age 32·8 ± 7·2 vs 33·5 ± 6·7 years and weight 100·9 ± 16·7 vs 99·3 ± 14·7 kg, respectively. At baseline, the PCOS group had higher testosterone 1·2 ± 0·3 vs 0·9 ± 0·3 nm (P = 0·01), HOMA-IR 5·1 ± 2·6 vs 3·5 ± 1·3 (P = 0·03), AST 22·4 ± 5·2 vs 18·8 ± 3·4 u/l (P = 0·04), PIIINP 4·4 ± 0·8 vs 3·5 ± 0·8 ug/ml (P = 0·01) and NAFLD seven (35%) vs none (P = 0·005), respectively. Twenty-five (69%) participants completed the study (13 PCOS, 12 controls). Following treatment, weight was reduced by 3·0 ± 4·2 kg (P = 0·01) and 3·8 ± 3·4 kg (P = 0·001), respectively. Similarly, HOMA-IR, hsCRP, triglycerides and urinary isoprostane significantly reduced in both groups. PIIINP significantly reduced the in PCOS group 4·4 ± 0·8 vs 3·7 ± 0·9 ug/ml (P < 0·01), but not in controls 3·5 ± 0·8 vs 3·2 ± 0·7 ug/ml (P = 0·08).

Conclusions: Treatment with liraglutide, and/or associated weight loss, significantly reduced PIIINP levels in obese women with PCOS. This may be an additional beneficial factor when considering the use of liraglutide in women with PCOS, obesity and NAFLD.