New analysis of semaglutide trial in adolescents shows it can lower liver enzymes indicating liver damage

A new sub-study of the STEP TEENS trial, presented at this year’s European Congress on Obesity (ECO) 2023 in Dublin May 17-20, shows that adolescents using semaglutide experienced significant reductions in liver enzyme levels which are an indicator of liver damage. The study is being conducted by Dr Daniel Weghuber, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria, and Dr Rasmus Sørrig, Novo Nordisk A/S (the manufacturer of semaglutide), Søborg, Denmark, and colleagues.

Increased body weight and body mass index (BMI) are associated with a greater incidence of non-alcoholic fat liver (NAFLD) and its advanced forms such as steatohepatitis, which can cause Hepatic insufficiency. Weight loss may improve liver parameters such as alanine aminotransferase (ALT) enzyme levels in patients with NAFLD/steatohepatitis. ALT measurements are considered the first step in screening children at risk for NAFLD. Consistently elevated ALT levels prompt further clinical testing for NAFLD or other diseases affecting the liver, while improved ALT levels indicate improvement in the underlying cause of liver damage.

The Phase 3, double-blind, placebo-controlled STEP TEENS trial demonstrated the efficacy and safety of semaglutide 2.4 mg once weekly for weight management in obese adolescents. This post-hoc analysis of the STEP TEENS trial examined changes in ALT and putative NAFLD levels in adolescents treated with semaglutide 2.4 mg compared to placebo.

Adolescents (aged 12 to A total of 201 participants were randomized (n=134 for semaglutide and n=67 for placebo). At baseline, the average age was 15.4 years, weight 107.5 kg, BMI 37.0 kg/m²; 62% were women; 38% had elevated ALT (42% in the semaglutide group and 30% in the placebo group) (corresponding to > 25.8 U/L in men, > 22.1 U/L in women); 34% were presumed to have NAFLD (37% semaglutide group and 27% placebo group) (defined as BMI > 85 percentile, fatty liver index [FLI, a surrogate index of fatty liver based on BMI, waist circumference, triglycerides and the liver enzyme gamma-glutamyl transferase] of 60 or more and high ALT).

The geometric mean ALT levels at baseline were 23 U/L versus 20 U/L in the semaglutide and placebo groups, respectively. The change in ALT from baseline with semaglutide was significantly greater compared to placebo (–18.1% versus -1.1%). At week 68, mean ALT levels decreased from baseline in semaglutide-treated participants who reached a weightloss ≥ 10%, but not in those who have it. placebo group, respectively. Among participants with elevated baseline ALT levels, 53.8% versus 33.3% had normal levels at week 68 with semaglutide versus placebo, respectively.

Participants reporting liver-related adverse events, which were mostly non-serious, were more numerous in the semaglutide 2.4 mg group (7.5%) than with placebo (1.5%). The imbalance was primarily due to events reported on the day of randomization (not exposure to semaglutide) and events in participants with pre-existing liver disorders.

The authors conclude: “In the STEP TEENS trial, treatment with semaglutide 2.4 mg once weekly for 68 weeks was associated with a significant reduction in levels of the liver enzyme alanine aminotransferase compared to placebo.”

Dr. Weghuber adds: “Fatty liver disease is the most common liver disease in adolescents with no drug treatment currently available. The results of this work are encouraging and will inform studies specifically designed to test semaglutide in adolescents with NAFLD.

Provided by the European Association for the Study of Obesity