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Updated: Jul 26, 2026
Detection of Protein Ubiquitination Sites by Peptide Enrichment and Mass Spectrometry
Published on: March 23, 2020
Proteomic signatures reflect effects of semaglutide treatment for MASH
Jörn M Schattenberg1, Henning Grønbæk2, Iris Kliers3
1Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany.
Background & Aims:
Proteomic technology has emerged as a non-invasive method for grading and staging metabolic dysfunction-associated steatohepatitis (MASH). The aims of this post hoc analysis of the STEP 1 and STEP 2 trials were to assess the distribution of SomaSignal-derived MASH components, evaluate the effect of semaglutide (2.4 mg and 1.0 mg) on these components, and test concordance with biopsy-based MASH histology from the phase IIb Sema-MASH trial.
Methods:
Participants with overweight or obesity (STEP 1) and type 2 diabetes (STEP 2), who received once-weekly semaglutide or placebo for 68 weeks and had available biological samples, were included. In addition, participants with biopsy-confirmed MASH from the phase IIb Sema-MASH trial who received once-daily semaglutide or placebo for 72 weeks were included.
Results:
SomaSignal-derived steatosis was prevalent in both STEP 1 (43.2%) and STEP 2 (71.7%). At week 68, participants who received semaglutide had significantly lower odds of exhibiting SomaSignal-defined MASH components compared with those on placebo. They were also more likely to have a less severe SomaSignal-derived stage of metabolic dysfunction-associated steatotic liver disease, with odds ratios for semaglutide 2.4 mg of 5.26 (95% CI 3.59-7.72) in STEP 1 and 4.90 (95% CI 2.86-8.40) in STEP 2; both p <0.0001. SomaSignal-derived MASH components correlated with histologic changes, standard liver-related biomarkers, and measures of glycemic control.
Conclusions:
These findings suggest that SomaSignal MASH component testing may be useful for evaluating the potential therapeutic effects of semaglutide in patients with MASH and related comorbidities. However, prospective randomized clinical trials are necessary to confirm these results.
Clinical Trial Registration Numbers:
STEP 1: NCT03548935; STEP 2: NCT03552757; MASH phase IIb trial: NCT02970942.
Impact And Implications:
Liver biopsy is the current gold standard for the diagnosis of metabolic dysfunction-associated steatohepatitis (MASH); however, this procedure is invasive and time consuming for patients living with MASH. The use of non-invasive tests to diagnose MASH is becoming increasingly popular and many clinicians see this approach as the diagnostic future. SomaSignal is a proteomics-based model designed to non-invasively test for and validate MASH components as well as detect the prevalence of metabolic dysfunction-associated steatotic liver disease stages, against biopsy results. In the future, SomaSignal MASH components may have an impact on future clinical practice by providing clinicians with an alternative option for non-invasive assessment of treatment effects in the early clinical stages of therapeutic development.
