Effect of liraglutide on ectopic fat in polycystic ovary syndrome: A randomized clinical trial

Abstract

Women with polycystic ovary syndrome (PCOS) were treated with the GLP-1 receptor agonist liraglutide to investigate the effect on liver fat content, visceral adipose tissue (VAT) and the prevalence of nonalcoholic fatty liver disease (NAFLD). In a double-blind, placebo-controlled, randomized clinical trial 72 women with PCOS, with a BMI > 25 kg/m and/or insulin resistance, were treated with liraglutide or received placebo 1.8 mg/d (2:1) for 26 weeks. Liver fat content was assessed by HMR spectroscopy, VAT by MRI, body composition by DXA, and glucose metabolism by oral glucose tolerance test. Compared with placebo, liraglutide treatment reduced body weight by 5.2 kg (5.6%), liver fat content by 44%, VAT by 18%, and the prevalence of NAFLD by two-thirds (all P< .01). Sex-hormone-binding-globulin (SHBG) levels increased by 19% (P = .03), and free testosterone decreased by 19% (P = .054). HbA1c, fasting glucose and leptin were reduced (all: P < .05), whereas measures of insulin resistance, adiponectin and glucagon did not change. In conclusion, 26 weeks of liraglutide treatment in PCOS resulted in significant reductions in liver fat content, VAT and the prevalence of NAFLD.

Effect of Weight Loss Medications on Hepatic Steatosis and Steatohepatitis: A Systematic Review

“…The study achieved the primary endpoint, demonstrating that 39% of patients in the liraglutide group compared to 9% in the placebo group met the primary endpoint of histological resolution of NASH without worsening of fibrosis (relative risk of The majority of studies that investigated changes in hepatic fat content with liraglutide or exenatide demonstrated benefit, and all studies of 16 weeks duration or longer with steatosis measured via imaging as an endpoint demonstrated benefit. Magnitude of benefit was approximately 30-45% relative reduction in fat content in most studies (19,22,34,44). Similarly, the majority of studies investigating serum markers of liver injury (ALT, AST, or GGT) demonstrated a benefit of liraglutide, with effect sizes ranging from quite modest (e.g., 5 U/L or less reduction in ALT) to ≥20 U/L and thus likely to be clinically meaningful.…”

“…Multiple publications have reported beneficial effects to reduce liver fat content and improve ALT, and one study has suggested a benefit in reducing progression of fibrosis (5,10,34,50). Twenty publications reported the effects of a GLP-1 analog on liverrelated endpoints; 12 of these investigated liraglutide (5,6,11,19,20,22,34,44,50,60,65,66), and 8 investigated exenatide (10,13,14,17,18,55,56,58). Four of these reported randomized, controlled, double-blind studies of liraglutide with a placebo (n = 3) or active (n = 1) comparator, and only one of these, the "Liraglutide Safety and Efficacy in Patients with Non-alcoholic Steatohepatitis (LEAN)" study, assessed histological endpoints using biopsy.…”

Das polyzystische Ovarsyndrom: Aktuelle Evidenz und praktische Empfehlungen

“…Der Effekt von Antidiabetika wie Liraglutid und Empagliflozin ist Gegenstand von Studien. Diese weisen vereinzelt positive Daten zur Reduktion von Gewicht, Hyperandrogenämie, Anovulation und zur Schwangerschaftsrate unter IVF auf [16][17][18][19][20]. Der Einsatz ist derzeit als experimentell zu betrachten und für die Patientinnen auch im Rahmen der Indikation der Lifestyle-Medikation oder eines Off-Label-Use kostenintensiv.…”

Incretin‐Based Therapies for the Management of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes

“…(15) But negative results have also been reported with sitagliptin in open-label studies (16,17) and in all three placebo-controlled trials. (18)(19)(20) Negative studies have been also reported with liraglutide, (20,21) but most have been positive with an improvement in hepatic steatosis (HS) (22)(23)(24)(25)(26)(27)(28) or liver histology. (29,30) This is usually proportional to the magnitude of weight loss, as reported for other short- (31) and long-acting (32) GLP-1RAs.…”