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Obesity shedding drug can cause liver damage in adolescents: Analysis

A new analysis of the trial of semaglutide in adolescents shows it can reduce liver enzymes, indicative of liver damage, according to a report presented at the 2023 European Congress on Obesity currently underway in Dublin, Ireland.

The substudy of the STEP TEENS trial, 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 further found that the participants in the semaglutide group reported mostly non-serious liver-related adverse events five times more than those in the placebo group (7.5% versus 1.5%).

However, they noted that the imbalance was mainly driven by events reported on the day of randomisation (not exposure to semaglutide) and events in participants with pre-existing liver disorders.

The imbalance was mainly driven by events reported on the day of randomisation (not exposure to semaglutide) and events in participants with pre-existing liver disorders.

Although the phase 3, double-blind, placebo-controlled STEP TEENS trial earlier demonstrated the efficacy and safety of semaglutide 2.4 mg once weekly for weight management among adolescents with obesity.

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This posthoc analysis of the trial examined the change in aminotransferase enzyme levels and presumed non-alcoholic fatty liver disease in adolescents treated with semaglutide 2.4 mg vs placebo and found that participants reporting liver-related adverse events, mostly non-serious, were higher in the semaglutide 2.4 mg group (7.5%) than with placebo (1.5%).

The analysis further revealed that estimated aminotransferase enzyme changes in participants with presumed non-alcoholic fatty liver disease were –15.5% vs +10.6% with semaglutide vs placebo group, respectively.

The analysis showed that of participants with elevated baseline aminotransferase enzyme levels, 53.8% vs 33.3% had normal levels at week 68 with semaglutide vs placebo, respectively.

Commenting on their findings, the authors concluded, “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.”

Pointing out that fatty liver disease is the most frequent liver disease in adolescents with no drug therapy currently available, Dr Weghuber added, "The results of this work are encouraging and will inform studies specifically designed to test semaglutide in adolescents with non-alcoholic fatty liver disease.” 


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