Ozempic boosts cardiometabolic markers, falls short for fibrosis in NASH-related cirrhosis
Click Here to Manage Email Alerts
LONDON — Ozempic improved cardiometabolic parameters and markers of liver injury yet failed to improve liver fibrosis in patients with nonalcoholic steatohepatitis and compensated cirrhosis, according to late-breaker data presented here.
“Patients with NASH and compensated cirrhosis are at a higher risk of liver-related and all-cause morbidity and mortality,” Rohit Loomba, MD, MHSc, director of hepatology and the NAFLD Research Center at UC San Diego School of Medicine, told attendees at the International Liver Congress. “In a previous phase 2b, placebo-controlled study in patients with NASH without cirrhosis, the glucagon-like peptide-1 analogue [Ozempic (semaglutide, Novo Nordisk)] improved NASH resolution, metabolic parameters and was well-tolerated.”
To determine whether the previously established safety and efficacy of semaglutide would apply to patients with NASH-related compensated cirrhosis, Loomba and colleagues randomized 71 adults with biopsy-confirmed NASH and compensated cirrhosis, BMI of at least 27 kg/m2 and HbA1c less than or equal to 9.5% to receive either 2.4 mg of semaglutide or placebo once weekly for 48 weeks.
The primary end point of the study — with histological parameters assessed at baseline and 48 weeks by a single pathologist — was the proportion of patients with at least one stage of liver fibrosis improvement without worsening of NASH after 48 weeks. Secondary endpoints included NASH resolution, changes in alanine- and aspartate-aminotransferase (ALT, AST), liver stiffness assessed by magnetic resonance elastography (MRE), liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF), cardiometabolic parameters and exploratory biomarkers, and adverse events.
According to study results, only 10.6% of patients who received semaglutide exhibited an improvement in liver fibrosis compared with 29.9% of patients on placebo, yet 34% exhibited NASH resolution compared with 20.8% of those on placebo.
The researchers observed that patients who received semaglutide had reduced AST (estimated treatment ratio (ETR) = 0.77), ALT (ETR = 0.76) and MRI-PDFF (ETR = 0.67) but not MRE (ETR = 0.93) vs. the placebo group.
In addition, patients with diabetes who received semaglutide exhibited reductions in HbA1c (P < .01) and body weight, as well as reduced triglycerides (ETR = 0.83, P = .01) and very LDL cholesterol (ETR = 0.83, P = .01).
“Although the primary endpoint was not met, once-weekly semaglutide 2.4 mg appeared safe and was well-tolerated in this 48-week trial in patients with NASH and compensated cirrhosis,” Loomba said. “Semaglutide 2.4 mg improved cardiometabolic parameters; it also improved noninvasive markers of liver injury associated with fibrosis progression.”
He added: “In a post-hoc exploratory analysis, there was no difference between treatments for the primary or secondary histology endpoints when evaluated either by a single pathologist or PathAI machine learning software.”
Collapse
Loomba R. Abstract LB001. Presented at: International Liver Congress; June 22-26, 2022; London (hybrid meeting).
Read more about
Click Here to Manage Email Alerts