Fig. 3: Improvements in MASH with semaglutide assessed by aptamer-based SomaSignal NASH tests.
a, Proportion of individuals with improvement in each MASH component. Improvement was defined as a negative SomaSignal test at week 72 in individuals with a positive test at baseline. Proportions of individuals with improvement were compared between semaglutide and placebo by a linear-by-linear association test for ordered data. ***P < 0.001. Analysis was two-sided with estimated treatment ratios derived from a multivariable-adjusted MMRM, with no adjustment for multiple testing. b, Volcano plots showing the estimated treatment ratio of semaglutide 0.4 mg/placebo and associated P value for all individual markers included in each SomaSignal NASH test. For each marker, the effect of semaglutide 0.4 mg versus placebo was tested in an MMRM analysis. Statistically significant treatment ratios of semaglutide 0.4 mg/placebo were evaluated using a two-sided Bonferroni-adjusted family-wise error rate of <0.1. Filled circles denote statistical significance; open circles denote no statistical significance. The presence of duplicate genes in b is due to two different targets covering the same gene and protein. ACP1, acid phosphatase 1; ACY1, aminoacylase-1; ADAMTSL2, a disintegrin and metalloproteinase with thrombospondin motifs-like protein 2; ADIPOQ, adiponectin; AKR1B10, aldo-keto reductase family 1 member B10; BPIFB1, bactericidal/permeability-increasing-fold-containing family B member 1; C1orf198, uncharacterized protein C1orf198; C7, complement component C7; CCL23, C-C motif chemokine 23; CNDP1, beta-Ala-His dipeptidase; CNN2, calponin-2; COLEC11, collectin-11; CTCF, transcriptional repressor CTCF; CTLA4, cytotoxic T-lymphocyte protein 4; ERN1, serine/threonine-protein kinase/endoribonuclease IRE1; FABP12, fatty acid-binding protein 12; FCGR3B, low-affinity immunoglobulin gamma Fc region receptor III-B; FCRL3, Fc receptor-like protein 3; GH2, growth hormone 2; GRID2, glutamate receptor ionotropic, δ-2; GSTZ1, maleylacetoacetate isomerase; GUSB, β-glucuronidase; HEXB, β-hexosaminidase B; INHBC, inhibin beta C chain; INSL5, insulin-like peptide 5; KDR, vascular endothelial growth factor receptor 2; NFASC, neurofascin; PCOLCE2, procollagen C-endopeptidase enhancer 2; PLOD3, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3; PTGR1, prostaglandin reductase 1; PYY, peptide YY; RECQL, ATP-dependent DNA helicase Q1; RPN1, dolichyl-diphosphooligosaccharide–protein glycosyltransferase subunit 1; SAA2, serum amyloid A-2 protein; TACSTD2, tumor-associated calcium signal transducer 2; TXNRD1, thioredoxin reductase 1; WNT5A, protein Wnt-5a.
