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A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis

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Harvard

Newsome, PN, Buchholtz, K, Cusi, K, Linder, M, Okanoue, T, Ratziu, V, Sanyal, AJ, Sejling, A-S, Harrison, SA & NN9931-4296 Investigators 2021, 'A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis', The New England journal of medicine, bind 384, nr. 12, s. 1113-1124. https://doi.org/10.1056/NEJMoa2028395

APA

Newsome, P. N., Buchholtz, K., Cusi, K., Linder, M., Okanoue, T., Ratziu, V., Sanyal, A. J., Sejling, A-S., Harrison, S. A., & NN9931-4296 Investigators (2021). A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. The New England journal of medicine, 384(12), 1113-1124. https://doi.org/10.1056/NEJMoa2028395

CBE

Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V, Sanyal AJ, Sejling A-S, Harrison SA, NN9931-4296 Investigators. 2021. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. The New England journal of medicine. 384(12):1113-1124. https://doi.org/10.1056/NEJMoa2028395

MLA

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Author

Newsome, Philip N ; Buchholtz, Kristine ; Cusi, Kenneth ; Linder, Martin ; Okanoue, Takeshi ; Ratziu, Vlad ; Sanyal, Arun J ; Sejling, Anne-Sophie ; Harrison, Stephen A ; NN9931-4296 Investigators. / A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. I: The New England journal of medicine. 2021 ; Bind 384, Nr. 12. s. 1113-1124.

Bibtex

@article{c951479fc55a468dac494b068fec0c6b,
title = "A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis",
abstract = "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.).",
author = "Newsome, {Philip N} and Kristine Buchholtz and Kenneth Cusi and Martin Linder and Takeshi Okanoue and Vlad Ratziu and Sanyal, {Arun J} and Anne-Sophie Sejling and Harrison, {Stephen A} and {NN9931-4296 Investigators}",
note = "Copyright {\textcopyright} 2020 Massachusetts Medical Society.",
year = "2021",
month = mar,
day = "25",
doi = "10.1056/NEJMoa2028395",
language = "English",
volume = "384",
pages = "1113--1124",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "12",

}

RIS

TY - JOUR

T1 - A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis

AU - Newsome, Philip N

AU - Buchholtz, Kristine

AU - Cusi, Kenneth

AU - Linder, Martin

AU - Okanoue, Takeshi

AU - Ratziu, Vlad

AU - Sanyal, Arun J

AU - Sejling, Anne-Sophie

AU - Harrison, Stephen A

AU - NN9931-4296 Investigators

N1 - Copyright © 2020 Massachusetts Medical Society.

PY - 2021/3/25

Y1 - 2021/3/25

N2 - 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.).

AB - 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.).

U2 - 10.1056/NEJMoa2028395

DO - 10.1056/NEJMoa2028395

M3 - Journal article

C2 - 33185364

VL - 384

SP - 1113

EP - 1124

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 12

ER -

ID: 61735551