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Background: Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known.Methods: We conducted a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients.Results: In total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients). The percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (P<0.001 for semaglutide 0.4 mg vs. placebo). An improvement in fibrosis stage occurred in 43% of the patients in the 0.4-mg group and in 33% of the patients in the placebo group (P = 0.48). The mean percent weight loss was 13% in the 0.4-mg group and 1% in the placebo group. The incidence of nausea, constipation, and vomiting was higher in the 0.4-mg group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%). Malignant neoplasms were reported in 3 patients who received semaglutide (1%) and in no patients who received placebo. Overall, neoplasms (benign, malignant, or unspecified) were reported in 15% of the patients in the semaglutide groups and in 8% in the placebo group; no pattern of occurrence in specific organs was observed.Conclusions: This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT02970942.). [ABSTRACT FROM AUTHOR]

Hypoglycemic events have been proven to be associated with measurable EEG changes. Several works in the literature have evaluated these changes by considering approaches at the single EEG channel level, but multivariate analyses have been scarcely investigated in Type 1 diabetes (T1D) subjects. The aim of the present work is to assess if and how hypoglycemia affects EEG coherence in a subset of EEG channels acquired in a hospital setting where eye- and muscle activation-induced artifacts are virtually absent. In particular, EEG multichannel data, acquired in 19 T1D hospitalized subjects undertaken to an insulin-induced hypoglycemia experiment, are considered. Computation of Partial Directed Coherence (PDC) through multivariate autoregressive models of P3-A1A2, P4-A1A2, C3-A1A2 and C4-A1A2 EEG channels shows that a decrease in the value of coherence, most likely related to the progressive loss of cognitive function and altered cerebral activity, occurs when passing from eu- to hypoglycemia, in both theta ([4, 8] Hz) and alpha ([8, 13] Hz) bands.