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New analysis of trial of semaglutide in adolescents shows it can reduce liver enzymes indicative of liver damage
A new substudy of the STEP TEENS trial presented at this year’s European Congress on Obesity (ECO 2023, Dublin 17-20 May) shows that adolescents using semaglutide experienced significant reductions in levels of liver enzymes that are an indicator of liver damage. The study is 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 fatty liver disease (NAFLD) and its advanced forms such as steatohepatitis, that can cause liver failure. Weight loss can improve liver parameters such as alanine aminotransferase enzyme (ALT) levels in patients with NAFLD/steatohepatitis. ALT measurements are considered the first step in NAFLD screening in children at risk. Consistently high levels of ALT prompt further clinical tests for NAFLD or other diseases affecting the liver, whereas improvement in ALT levels indicates 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 among adolescents with obesity. This post-hoc analysis of the STEP TEENS trial examined the change in ALT levels and presumed NAFLD in adolescents treated with semaglutide 2.4 mg vs placebo.
Adolescents (aged 12 to <18 years) with obesity (BMI ≥95th percentile), or overweight (BMI ≥85th to <95th percentile) with at least one weight-related comorbidity, were randomised 2:1 after a 12-week lifestyle intervention run-in phase to receive semaglutide 2.4 mg once weekly (or maximum tolerated dose) or placebo for 68 weeks, plus lifestyle intervention. Change in ALT from baseline to week 68 was a prespecified secondary endpoint in the STEP TEENS trial.
Overall, 201 participants were randomised (n=134 for semaglutide and n=67 for placebo). At baseline, mean age was 15.4 years, body weight 107.5 kg, BMI 37.0 kg/m2; 62% were female; 38% had elevated ALT (42% in the semaglutide group and 30% in the placebo group) (corresponding to >25.8 U/L in males, >22.1 U/L in females); 34% were presumed to have NAFLD (37% of the semaglutide group and 27% in the placebo group) (defined as BMI in >85th 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 above and elevated ALT).
The geometric mean ALT level at baseline was 23 U/L vs 20 U/L in the semaglutide and placebo groups, respectively. The change from baseline in ALT with semaglutide was significantly greater vs placebo (–18.1% vs –1.1%). At week 68, mean ALT levels decreased from baseline levels in participants treated with semaglutide who achieved a weight loss of ≥10%, but not in those with <10% weight loss (See Table 1 abstract).
Estimated ALT changes in participants with presumed NAFLD were –15.5% vs +10.6% with semaglutide vs placebo group, respectively (Table 1). Of participants with elevated baseline ALT levels, 53.8% vs 33.3% had normal levels at week 68 with semaglutide vs placebo, respectively.
Participants reporting liver-related adverse events, which were mostly non-serious, were higher in the semaglutide 2.4 mg group (7.5%) than with placebo (1.5%). The imbalance was mainly driven by events reported at the day of randomisation (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 of levels of the liver enzyme alanine aminotransferase compared with placebo.”
Dr Weghuber adds: “Fatty liver disease is the most frequent liver disease in adolescents with no drug therapy currently available. The results of this work are encouraging and will inform studies specifically designed to test semaglutide in adolescents with NAFLD.”
