Novo Nordisk reports normal liver fat in 23 of 26 Wegovy users
A small post hoc MRI subgroup improved after 72 weeks, while placebo comparisons came from other liver measures in the larger STEP UP dataset.
Adrian Kessler
Normal liver-fat readings were recorded in 23 of 26 Wegovy users who started above the threshold, as Novo Nordisk A/S NYSENVO disclosed a post hoc STEP UP analysis on Thursday. MRI measurements in the treated subgroup averaged 3.1 per cent at week 72, down from 8.8 per cent at baseline.
The MRI subset included 55 people from the STEP UP obesity trial, and 40 received one of two semaglutide doses, according to the company's presentation. Novo's release gives no placebo MRI result, so the reported change describes what happened within the treatment group rather than a difference against control.
Novo is a large Danish drugmaker that sells diabetes and obesity medicines worldwide.
Novo's U.S. shares closed at US$37.91 in New York on Sept. 30 at 4 p.m. EDT, according to NYSENVO. The analysis adds a liver-fat measure to the evidence for Wegovy, but the measured subgroup is much smaller than the parent trials.
MRI Findings Came From a Small Treated Subgroup
The pooled STEP UP analysis covered 1,919 adults in two phase 3b trials involving people with obesity, with and without diabetes. The higher-dose semaglutide group had 1,312 participants, the lower-dose group 304. Another 303 received placebo.
Those trials were designed around body-weight change and the proportion achieving at least five per cent weight loss after 72 weeks. The liver-imaging measure was examined later, and Novo pooled the two active doses for its MRI finding. The presentation calls its analyses descriptive and supplies no p value or confidence interval for the MRI result.
The larger pooled dataset did allow comparisons with placebo on other liver measures. Among participants with elevated baseline ALT, a liver enzyme, median levels fell by 16 units per litre in either semaglutide group, versus 7.5 units per litre on placebo at week 72. Those figures are enzyme changes, not MRI readings.
Among those classified as high risk by the fatty-liver index at baseline, 42.9 per cent on the higher dose moved to a lower risk category. The corresponding figures were 32.3 per cent on the lower dose and 10.7 per cent on placebo, according to the presentation. That index uses body measurements and blood tests; it is not a liver biopsy or a MASH diagnosis.
"This analysis showed that semaglutide reduced liver fat and was linked to better overall liver health in adults with obesity," Eric Lawitz of the Texas Liver Institute said in Novo's release.
The MRI subgroup's liver measures alone cannot establish a new comparative safety profile. Nor can normalization of fat on imaging show whether inflammation or fibrosis has reversed in someone with metabolic dysfunction-associated steatohepatitis, or MASH.
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MASH Approval Rests on a Separate Trial
As of Oct. 1, Novo said Wegovy at 2.4 milligrams was already approved for MASH in the United States and Canada, among other markets. It also said the 7.2-milligram dose in STEP UP is not being investigated for MASH. The new analysis therefore does not establish an additional approved MASH dose.
Novo's ESSENCE trial enrolled 1,197 people with MASH and moderate to advanced fibrosis to compare semaglutide at 2.4 milligrams with placebo. Its first part used liver biopsies after 72 weeks to assess disease changes; the company expects results from the longer second part in 2029. That trial, rather than the STEP UP MRI subgroup, addresses the disease outcomes behind the approved MASH use.
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Novo's financial calendar lists Nov. 4 for its next quarterly results. That report will give investors the next scheduled look at sales performance after the new liver analysis.
