New Analysis of Semaglutide Trial in Adolescents Shows Semaglutide May Decrease Liver Enzymes Marking Liver Damage

Sub Levels

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A new substudy of the STEP TEENS trial, presented at this year’s European Obesity Conference (ECO) 2023 in Dublin, May 17-20, shows that adolescents using semaglutide improved liver enzyme levels indicative of liver damage. It is shown to have experienced a significant decline. The study was done by Dr. Daniel Wegber, Department of Pediatrics, Paracelsus Medical School, Salzburg, Austria, and Dr. Rasmus Sourig, Novohi Nordisk A/S (manufacturer of semaglutide), Soborg, Denmark, and his colleagues. is.

Increased body weight and body mass index (BMI) are associated with increased incidence of non-alcoholic fatty liver disease (NAFLD) and its advanced forms, such as steatohepatitis, which can lead to liver failure. In patients with NAFLD/steatohepatitis, weight loss may improve liver parameters such as alanine aminotransferase enzyme (ALT) levels. ALT measurement is considered the first step in his NAFLD screening in at-risk children. Consistently elevated ALT levels prompt further laboratory investigations for NAFLD or other diseases that affect the liver, whereas improvements in ALT levels indicate an improvement in the underlying cause of liver damage.

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

Obese (BMI ≥ 95th percentile) or overweight (BMI ≥ 85 to 95th percentile) adolescents (aged ≥12 years and <18 years) with at least one weight-related comorbidity, 2:1 after 12 weeks of lifestyle intervention randomized with. An induction phase of semaglutide 2.4 mg once weekly (or the maximum tolerated dose) or placebo for 68 weeks plus a lifestyle intervention. Change in ALT from baseline to week 68 was a prespecified secondary endpoint in the STEP TEENS trial.

Overall, 201 participants were randomized (n=134 for semaglutide and n=67 for placebo).. Mean age at baseline was 15.4 years, weight was 107.5 kg, and BMI was 37.0 kg/m3.262% were female. Thirty-eight percent had elevated ALT (42% in the semaglutide group and 30% in the placebo group) (equivalent to >25.8 U/L in men and >22.1 U/L in women). 34% were estimated to have NAFLD (37% in the semaglutide group, 27% in the placebo group) (BMI ≥85th percentile, defined as fatty liver index) [FLI, a surrogate index of fatty liver based on BMI, waist circumference, triglycerides and the liver enzyme gamma-glutamyl transferase] 60 or higher and elevated ALT).

Geometric mean ALT levels at baseline were 20 U/L versus 23 U/L in the semaglutide and placebo groups, respectively. The change from baseline in ALT was significantly greater with semaglutide compared with placebo (-18.1% vs -1.1%). At week 68, mean ALT levels decreased from baseline levels in semaglutide-treated participants who achieved ≥10% weight loss, but not in participants who achieved <10% weight loss .

Estimated ALT change in participants with presumed NAFLD was -15.5% vs +10.6% in the semaglutide and placebo groups, respectively. Of participants with elevated baseline ALT levels, 53.8% and 33.3% had normal levels at week 68 in the semaglutide and placebo groups, respectively.

More participants in the semaglutide 2.4 mg group (7.5%) reported liver-related adverse events (mostly nonserious) than in the placebo group (1.5%). This imbalance was primarily caused by events reported on the day of randomization (not semaglutide exposure) and events in participants with pre-existing liver injury.

The authors conclude, “In the STEP TEENS trial, semaglutide 2.4 mg once weekly for 68 weeks was associated with significantly lower liver enzyme alanine aminotransferase levels compared with placebo.”

Dr. Weghuber said, “Fat liver disease is the most common liver disease in adolescents for which there is currently no pharmacological therapy available. The results of this study are encouraging, as it was specifically designed to test semaglutide in adolescents with NAFLD. It will inform future research,” he added.

Courtesy of the European Obesity Society

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