Fig. 4: Semaglutide treatment effect on biomarkers included in the aptamer-based SomaScan assay.
a, Heatmap showing the 14 markers found to constitute the aptamer-based proteomic signature of semaglutide treatment. Data mining was performed using the repeated LASSO procedure including all 4,979 markers in the SomaScan assay as input. For each marker, change from baseline at week 72 was used as predictor variable. The heatmap shows individual changes in protein expression from baseline to week 72 on an arbitrary scale. b, Box plot showing the treatment effect of placebo and semaglutide 0.1 mg, 0.2 mg and 0.4 mg on the 14-marker proteomic signature of semaglutide. The treatment effect was calculated from the average LASSO coefficients for each of the 14 markers and is presented on an arbitrary scale. The number of patients is the on-treatment population for each treatment group. a.u., arbitrary units. c, Volcano plot showing the estimated treatment ratio of semaglutide 0.4 mg/placebo at week 72 and associated P value for all 4,979 individual markers included in the SomaScan assay. 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. Blue dots denote statistical significance; gray dots denote no statistical significance. Red circles show the 14 markers included in the proteomic signature of semaglutide treatment (see b). ACAN, aggrecan core protein; ADAMTSL2, a disintegrin and metalloproteinase with thrombospondin motifs-like protein 2; CD163, scavenger receptor cysteine-rich type 1 protein M130; CHAD, chondroadherin; CRISP2, cysteine-rich secretory protein 2; LECT2, leukocyte cell-derived chemotaxin-2; MLN, promotilin; PNLIPRP1, inactive pancreatic lipase-related protein 1; PRSS2, trypsin-2; PRSS3, trypsin-3; PTGR1, prostaglandin reductase 1; REG3A, regenerating islet-derived protein 3 alpha; RET, (REarranged during Transfection) receptor tyrosine kinase; SHBG, sex hormone-binding globulin.
