Liver Health Belongs in Obesity Care Conversations, Expert Says

In an interview with Pharmacy Times, Eric Lawitz, MD, FAASLD, AGAF, FAPCR, CPI, vice president of scientific and research development at The Texas Liver Institute and clinical professor of medicine at the University of Texas Health San Antonio, discussed a post hoc analysis of the STEP UP and STEP UP T2D trials on semaglutide and liver health. Lawitz said liver health belongs in routine obesity care conversations, not only after a diagnosis of metabolic dysfunction–associated steatotic liver disease (MASLD) or metabolic dysfunction–associated steatohepatitis (MASH), because liver fat often builds up without symptoms. He encouraged pharmacists to prompt patients, especially those with type 2 diabetes, to ask their clinician about liver disease risk, starting with a FIB-4 score. Among participants with elevated liver enzymes at baseline, median ALT fell by 16 U/L with either semaglutide dose vs 7.5 U/L with placebo, and 88.5% of participants in an MRI subgroup with elevated liver fat reached normal levels. Lawitz said pharmacists should keep the approved MASH indication, at the 2.4-mg dose, separate from possible liver benefits seen in obesity treatment.

Pharmacy Times: How should pharmacists talk about liver health with patients with obesity who haven't been diagnosed with metabolic dysfunction–associated steatotic liver disease (MASLD) or metabolic dysfunction–associated steatohepatitis (MASH)?

Eric Lawitz, MD, FAASLD, AGAF, FAPCR, CPI: Liver health belongs in the routine conversation about obesity and metabolic health. It shouldn't come up only after someone is diagnosed with MASLD or MASH. Pharmacists can tell patients that fat often builds up in the liver in people with obesity, and that this usually causes no symptoms. They can encourage patients to ask their clinician about their liver disease risk, especially patients who also have type 2 diabetes or other metabolic risk factors. Simple tests, starting with the Fibrosis-4 (FIB-4) score from routine blood work, can show who needs further evaluation for liver scarring.

Our analysis is encouraging: treating obesity with semaglutide (Wegovy; Novo Nordisk) may also improve measures of liver health. In STEP UP and STEP UP T2D, both semaglutide doses lowered liver enzymes when elevated at baseline and improved liver fat in those with elevated liver fat at baseline. In the smaller STEP UP magnetic resonance imaging (MRI) subgroup, 88.5% of semaglutide-treated participants who started with elevated liver fat had normal liver fat by week 72.

Pharmacy Times: With only the 2.4-mg dose approved for MASH, how should pharmacists think about liver benefit for patients on semaglutide 7.2 mg?

Lawitz: Pharmacists should keep 2 things separate: the approved MASH indication and possible liver benefits in patients taking semaglutide for obesity. The recommended dose for MASH is 2.4 mg. At baseline, participants in these obesity trials had a high likelihood of liver fat (steatosis) but a low likelihood of significant fibrosis.

What we did see was improvement in liver-related measures. Among participants who started with elevated liver enzymes, median alanine aminotransferase (ALT) fell by 16 U/L with either dose, compared with 7.5 U/L with placebo. We also saw a dose-dependent shift toward lower-risk steatosis categories. The MRI analysis was a small subgroup, but 88.5% of participants with elevated liver fat at baseline reached normal levels (below 5%) by the end of treatment. These are promising signals for semaglutide across the spectrum of MASLD.