A Phase 2 interventional study of Semaglutide and Placebo (semaglutide) in Non-alcoholic Steatohepatitis, sponsored by Novo Nordisk A/S. Completed at 38 sites in 5 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-05-29.
Sponsored by Novo Nordisk A/S · Phase 2, Interventional, and Treatment
Semaglutide is a medicine studied in patients with non-alcoholic steatohepatitis (NASH), as it may improve liver damage. Participants will either get semaglutide or placebo (a dummy medicine) - which treatment participants get is decided by chance. The study will last for about 61 weeks in total. Participants will have 10 clinic visits and 3 phone calls with the study doctor or staff during the study. Some of the clinic visits may be spread over more days. Participants will need to inject themselves with medicine under the skin. Participants will have to do this once a week for 48 weeks. The study includes magnetic resonance imaging (MRI) scans of the liver, 1 or 2 liver tissue samples, ultrasound scans of the stomach and a possible examination of the food pipe. For some tests participants may need to remove some items of clothing. Participants will stop in the study if the doctor thinks that there are any risks for their health. The information collected from participants during the study may help them and other patients with NASH in the future. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.
1,507 studies on the registry are indexed under Non-alcoholic Fatty Liver Disease; 303 are open to participants now.
This study's enrollment of 71 is above the median of 60 across 1,098 interventional studies indexed under Non-alcoholic Fatty Liver Disease.
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Exclusion Criteria:
Dose escalation to 2.4 mg of semaglutide once-weekly
Drug: Semaglutide
Semaglutide placebo once-weekly
Drug: Placebo (semaglutide)
Semaglutide given subcutaneously (s.c., under the skin) once-weekly for 48 weeks
Semaglutide placebo s.c. given once-weekly for 48 weeks
Percentage of Participants With At Least One Stage of Liver Fibrosis Improvement With No Worsening of Non-Alcoholic Steatohepatitis (NASH) After 48 Weeks
NASH resolution defined by NASH clinical research network (CRN) as lobular inflammation of 0 or 1; hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, higher scores indicating more severe hepatocellular ballooning/lobular inflammation. Worsening of NASH defined by NASH CRN as increase of at least 1 stage of either lobular inflammation, hepatocyte ballooning or steatosis. Worsening of fibrosis defined by increase in fibrosis at least 1 stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Week 48
Change From Baseline in Liver Fat Content Measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)-Ratio to Baseline
Change in liver fat content (measured as percentage) from baseline to week 48 is presented as ratio to baseline. Liver fat content was assessed via MRI-PDFF technique and results were measured in percentage. MRI-PDFF utilized a gradient echo sequence with low flip angle to minimize T1 bias, corrected T2\* decay (due to iron overload) via modeling of the fat signal as a superposition of multiple frequency components from 5 different lipid types, and was applied in each of the 9 Couinaud segments. This technique improved fat quantification accuracy for the entire liver permitting quantification of small differences/changes following pharmacological intervention. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Liver Stiffness Measured by Magnetic Resonance Elastography (MRE)-Ratio to Baseline
Change in Liver Stiffness from baseline to week 48 is presented as ratio to baseline. Liver stiffness was measured in kilopascal using MRE. MRE is a technology that uses MRI imaging with low-frequency vibrations to create a visual map (elastogram) that shows stiffness of the liver. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With NASH Resolution After 48 Weeks
NASH resolution defined by NASH clinical research network as lobular inflammation of 0 or 1 and hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation. Worsening of fibrosis defined by an increase in fibrosis at least one stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Week 48
Change From Baseline in Fibrosis-4 Score-Ratio to Baseline
Change in fibrosis-4 score from baseline to week 48 is presented as ratio to baseline. Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and age that was calculated using formula: Fibrosis-4 = (Age \[years\] x AST \[units per liter (U/L)\]) / (platelets \[10\^9 cells/L\] x (square root of ALT \[U/L\])). A Fibrosis-4 index of \< 1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Change in Non-Alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS)
Percentage of participants who had worsened, improved or had no change in total NAS from baseline to week 48 or missing data is presented. Worsening was defined as an increase of at least 1 in the NAS; Improvement was defined as a decrease of at least 1 in the NAS; while no change corresponds to no change in NAS and missing refers to participants with missing outcomes for NAS from baseline to week 48. NAS was calculated as the sum of scores for steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocyte ballooning (0 to 2). Therefore, it is assessed on a scale of 0-8, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Change in The Fibrosis Stage According to The Kleiner Fibrosis Classification
Percentage of participants who had improved, worsened, or had no change in fibrosis stage from baseline to week 48 or missing data is presented. The degree of fibrosis was described by the Kleiner fibrosis staging system, ranging from F0 (absence of fibrosis), F1 (portal/perisinusoidal fibrosis), F2 (perisinusoidal and portal/periportal fibrosis), F3 (septal or bridging fibrosis) through F4 (cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Change in Hepatocyte Ballooning
Percentage of participants who had improved, worsened, or had no change in hepatocyte ballooning from baseline to week 48 or missing data is presented. Hepatocyte ballooning was assessed on a scale of 0-2, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Change in Lobular Inflammation
Percentage of participants who had improved, worsened, or had no change in lobular inflammation from baseline to week 48 or missing data is presented. Lobular inflammation was assessed on a scale of 0-3, with higher scores indicating more severe lobular inflammation. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Change in Steatosis
Percentage of participants who had improved, worsened, or had no change in steatosis from baseline to week 48 or missing data is presented. Steatosis was assessed on a scale of 0-3, with higher scores indicating more severe steatosis. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Change in The Steatosis-Activity-Fibrosis (SAF) Activity Component Score
Percentage of participants who had improved, worsened, or had no change in the activity component of the SAF score from baseline to week 48 or missing data is presented. SAF score was assessed on a scale of 0-4, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Change in The Ishak Fibrosis Score
Percentage of participants who had improved, worsened, or had no change in the Ishak fibrosis score from baseline to week 48 or missing data is presented. Ishak fibrosis score was assessed on a scale of 0-6, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Hepatic Collagen
Change in hepatic collagen from baseline to week 48 was analysed. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Improvement in Fibrosis Stage According to The Kleiner Fibrosis Classification (Yes/No)
Improvement is defined as at least one stage decrease from baseline to week 48 in Kleiner fibrosis classification. The degree of fibrosis was described by the Kleiner fibrosis staging system, ranging from F0 (absence of fibrosis), F1 (portal/perisinusoidal fibrosis), F2 (perisinusoidal and portal/periportal fibrosis), F3 (septal or bridging fibrosis) through F4 (cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Improvement in Hepatocyte Ballooning (Yes/No)
Improvement is defined as at least one stage decrease from baseline to week 48 in hepatocyte ballooning clinical research network (CRN) score. Hepatocyte ballooning was assessed on a scale of 0-2, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Improvement in Lobular Inflammation (Yes/No)
Improvement is defined as at least one stage decrease from baseline to week 48 in lobular inflammation CRN score. Lobular inflammation was assessed on a scale of 0-3, with higher scores indicating more severe lobular inflammation. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Improvement in Steatosis (Yes/No)
Improvement is defined as at least one stage decrease from baseline to week 48 in steatosis CRN score. Steatosis was assessed on a scale of 0-3, with higher scores indicating more severe steatosis. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Improvement in NAS (Yes/No)
Improvement is defined as at least one stage decrease from baseline to week 48 in NAS. NAS was calculated as the sum of scores for steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocyte ballooning (0 to 2). Therefore, it is assessed on a scale of 0-8, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Improvement in SAF Activity Component Score (Yes/No)
Improvement is defined as at least one stage decrease from baseline to week 48 in SAF score. SAF score was assessed on a scale of 0-4, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Improvement in Ishak Fibrosis Score (Yes/No)
Improvement is defined as at least one stage decrease from baseline to week 48 in Ishak fibrosis score. Ishak fibrosis score was assessed on a scale of 0-6, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Body Weight
Change in body weight from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Relative Change From Baseline in Body Weight
Relative change in body weight (measured as kg) from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Waist Circumference
Change in waist circumference from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Body Mass Index (BMI)
Change in BMI from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Percentage of Participants With Weight Loss of >= 5% of Baseline Body Weight at Week 48
Percentage of participants with weight loss of greater than or equal to (≥) 5% of baseline body weight at 48 weeks is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Week 48
Percentage of Participants With Weight Loss of >= 10% of Baseline Body Weight at Week 48
Percentage of participants with weight loss of ≥ 10% of baseline body weight at 48 weeks is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Week 48
Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c)
Change in HbA1c from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Fasting Plasma Glucose (FPG)
Change in FPG from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Fasting C-peptide-Ratio to Baseline
Change in fasting C-peptide \[measured as nanomoles per litre (nmol/L)\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Systolic And Diastolic Blood Pressure
Change in systolic and diastolic blood pressure from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Total Cholesterol-Ratio to Baseline
Change in total cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol-Ratio to Baseline
Change in LDL cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol-Ratio to Baseline
Change in HDL cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol-Ratio to Baseline
Change in VLDL cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Triglycerides-Ratio to Baseline
Change in triglycerides (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Free Fatty Acids (FFA)-Ratio to Baseline
Change in free fatty acids (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline
Change in hsCRP (measured as milligrams per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Alanine Aminotransferase (ALT)-Ratio to Baseline
Change in ALT (measured as units per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Aspartate Aminotransferase (AST)-Ratio to Baseline
Change in AST (measured as units per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Gamma-Glutamyl Transferase (GGT)-Ratio to Baseline
Change in GGT (measured as units per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Albumin-Ratio to Baseline
Change in albumin \[measured as grams per deciliter (g/dL)\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Changes From Baseline in Thrombocytes-Ratio to Baseline
Change in thrombocytes \[measured as 10\^9 cells per liter\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in International Normalized Ratio (INR)-Ratio to Baseline
Change in INR from baseline to week 48 is presented as ratio to baseline. INR is the ratio of measured prothrombin time over normal prothrombin time and it evaluates the extrinsic coagulation pathway (vitamin K dependent clotting factors II; V, VII, IX and X). These clotting factors are synthesised in the liver, thus INR is used as a marker of liver synthesis function. The therapeutic INR range varies, most commonly an INR 2-3 goal, but ranging from 1.5-4.0. Bleeding complications are more likely to occur above an INR value of 4.0. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Direct Bilirubin-Ratio to Baseline
Change in direct bilirubin \[measured as micromoles per liter (umol/L)\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Change From Baseline in Total Bilirubin-Ratio to Baseline
Change in total bilirubin \[measured as umol/L\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
Time frame: Baseline (week 0), Week 48
Number of Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a clinical trial participant administered or using a medicinal product, whether or not considered related to the medicinal product or usage. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. Outcome measure was evaluated based on data from on-treatment period which started on the date of first administration of trial product and ended on the date of whatever comes first of: a) last dose of trial product + 49 days (7 half-lives of semaglutide), b) follow-up visit (week 55), or c) end of the in-trial period.
Time frame: From baseline (week 0) to week 55
Number of Treatment-Emergent Hypoglycaemic Episodes
Hypoglycaemic episode (blood glucose less than or equal to (\<=) 3.9 mmol/L \[70 milligrams per decilitre (mg/dL)\] Or greater than (\>) 3.9 mmol/L (70 mg/dL) occurring in conjunction with hypoglycaemic symptoms) is defined as treatment emergent if the onset of the episode occurs during the on-treatment period. Outcome measure was evaluated based on data from on-treatment period which started on the date of first administration of trial product and ended on the date of whatever comes first of: a) last dose of trial product + 49 days (7 half-lives of semaglutide), b) follow-up visit (week 55), or c) end of the in-trial period.
Time frame: From baseline (week 0) to week 55
Change From Baseline in Pulse
Change in pulse from baseline to week 48 is presented. Outcome measure was evaluated based on data from on-treatment period which started on the date of first administration of trial product and ended on the date of whatever comes first of: a) last dose of trial product + 49 days (7 half-lives of semaglutide), b) follow-up visit (week 55), or c) end of the in-trial period.
Time frame: Baseline (week 0), Week 48
The trial was conducted at 38 sites in 5 countries as follows (number of sites that screened subjects/ number of sites that randomised subjects): United States (24/19); United Kingdom (4/3); Germany (3/2); France (5/3); Spain (2/2).
| Milestone | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Started | 47 | 24 |
| Completed | 45 | 23 |
| Not completed | 2 | 1 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 |
NASH resolution defined by NASH clinical research network (CRN) as lobular inflammation of 0 or 1; hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, higher scores indicating more severe hepatocellular ballooning/lobular inflammation. Worsening of NASH defined by NASH CRN as increase of at least 1 stage of either lobular inflammation, hepatocyte ballooning or steatosis. Worsening of fibrosis defined by increase in fibrosis at least 1 stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Percentage of Participants With At Least One Stage of Liver Fibrosis Improvement With No Worsening of Non-Alcoholic Steatohepatitis (NASH) After 48 Weeks | 10.6 | 29.2 |
Change in liver fat content (measured as percentage) from baseline to week 48 is presented as ratio to baseline. Liver fat content was assessed via MRI-PDFF technique and results were measured in percentage. MRI-PDFF utilized a gradient echo sequence with low flip angle to minimize T1 bias, corrected T2\* decay (due to iron overload) via modeling of the fat signal as a superposition of multiple frequency components from 5 different lipid types, and was applied in each of the 9 Couinaud segments. This technique improved fat quantification accuracy for the entire liver permitting quantification of small differences/changes following pharmacological intervention. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of liver fat content | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Liver Fat Content Measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF)-Ratio to Baseline | 0.62 ± 63.38 | 1.01 ± 34.46 |
Change in Liver Stiffness from baseline to week 48 is presented as ratio to baseline. Liver stiffness was measured in kilopascal using MRE. MRE is a technology that uses MRI imaging with low-frequency vibrations to create a visual map (elastogram) that shows stiffness of the liver. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of liver stiffness | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Liver Stiffness Measured by Magnetic Resonance Elastography (MRE)-Ratio to Baseline | 0.87 ± 22.24 | 0.98 ± 28.51 |
NASH resolution defined by NASH clinical research network as lobular inflammation of 0 or 1 and hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation. Worsening of fibrosis defined by an increase in fibrosis at least one stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Percentage of Participants With NASH Resolution After 48 Weeks | 34.0 | 20.8 |
Change in fibrosis-4 score from baseline to week 48 is presented as ratio to baseline. Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and age that was calculated using formula: Fibrosis-4 = (Age \[years\] x AST \[units per liter (U/L)\]) / (platelets \[10\^9 cells/L\] x (square root of ALT \[U/L\])). A Fibrosis-4 index of \< 1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of fibrosis-4 score | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Fibrosis-4 Score-Ratio to Baseline | 0.9 ± 30.7 | 1.0 ± 38.0 |
Percentage of participants who had worsened, improved or had no change in total NAS from baseline to week 48 or missing data is presented. Worsening was defined as an increase of at least 1 in the NAS; Improvement was defined as a decrease of at least 1 in the NAS; while no change corresponds to no change in NAS and missing refers to participants with missing outcomes for NAS from baseline to week 48. NAS was calculated as the sum of scores for steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocyte ballooning (0 to 2). Therefore, it is assessed on a scale of 0-8, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Improvement | 61.7 | 58.3 |
| Worsening | 2.1 | 16.7 |
| No change | 21.3 | 20.8 |
| Missing | 14.9 | 4.2 |
Percentage of participants who had improved, worsened, or had no change in fibrosis stage from baseline to week 48 or missing data is presented. The degree of fibrosis was described by the Kleiner fibrosis staging system, ranging from F0 (absence of fibrosis), F1 (portal/perisinusoidal fibrosis), F2 (perisinusoidal and portal/periportal fibrosis), F3 (septal or bridging fibrosis) through F4 (cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Improvement | 12.8 | 33.3 |
| Worsening | 0.0 | 0.0 |
| No change | 72.3 | 62.5 |
| Missing | 14.9 | 4.2 |
Percentage of participants who had improved, worsened, or had no change in hepatocyte ballooning from baseline to week 48 or missing data is presented. Hepatocyte ballooning was assessed on a scale of 0-2, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Improvement | 55.3 | 33.3 |
| Worsening | 2.1 | 8.3 |
| No change | 27.7 | 54.2 |
| Missing | 14.9 | 4.2 |
Percentage of participants who had improved, worsened, or had no change in lobular inflammation from baseline to week 48 or missing data is presented. Lobular inflammation was assessed on a scale of 0-3, with higher scores indicating more severe lobular inflammation. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Improvement | 42.6 | 37.5 |
| Worsening | 12.8 | 12.5 |
| No change | 29.8 | 45.8 |
| Missing | 14.9 | 4.2 |
Percentage of participants who had improved, worsened, or had no change in steatosis from baseline to week 48 or missing data is presented. Steatosis was assessed on a scale of 0-3, with higher scores indicating more severe steatosis. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Improvement | 44.7 | 33.3 |
| Worsening | 2.1 | 16.7 |
| No change | 38.3 | 45.8 |
| Missing | 14.9 | 4.2 |
Percentage of participants who had improved, worsened, or had no change in the activity component of the SAF score from baseline to week 48 or missing data is presented. SAF score was assessed on a scale of 0-4, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Improvement | 57.4 | 50.0 |
| Worsening | 8.5 | 12.5 |
| No change | 19.1 | 33.3 |
| Missing | 14.9 | 4.2 |
Percentage of participants who had improved, worsened, or had no change in the Ishak fibrosis score from baseline to week 48 or missing data is presented. Ishak fibrosis score was assessed on a scale of 0-6, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Improvement | 27.7 | 37.5 |
| Worsening | 2.1 | 12.5 |
| No change | 55.3 | 45.8 |
| Missing | 14.9 | 4.2 |
Change in hepatic collagen from baseline to week 48 was analysed. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of hepatic collagen | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Hepatic Collagen | -1.7 ± 7.9 | -1.2 ± 5.1 |
Improvement is defined as at least one stage decrease from baseline to week 48 in Kleiner fibrosis classification. The degree of fibrosis was described by the Kleiner fibrosis staging system, ranging from F0 (absence of fibrosis), F1 (portal/perisinusoidal fibrosis), F2 (perisinusoidal and portal/periportal fibrosis), F3 (septal or bridging fibrosis) through F4 (cirrhosis). Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Yes | 12.8 | 33.3 |
| No | 72.3 | 62.5 |
| Missing | 14.9 | 4.2 |
Improvement is defined as at least one stage decrease from baseline to week 48 in hepatocyte ballooning clinical research network (CRN) score. Hepatocyte ballooning was assessed on a scale of 0-2, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Yes | 55.3 | 33.3 |
| No | 29.8 | 62.5 |
| Missing | 14.9 | 4.2 |
Improvement is defined as at least one stage decrease from baseline to week 48 in lobular inflammation CRN score. Lobular inflammation was assessed on a scale of 0-3, with higher scores indicating more severe lobular inflammation. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Yes | 42.6 | 37.5 |
| No | 42.6 | 58.3 |
| Missing | 14.9 | 4.2 |
Improvement is defined as at least one stage decrease from baseline to week 48 in steatosis CRN score. Steatosis was assessed on a scale of 0-3, with higher scores indicating more severe steatosis. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Yes | 44.7 | 33.3 |
| No | 40.4 | 62.5 |
| Missing | 14.9 | 4.2 |
Improvement is defined as at least one stage decrease from baseline to week 48 in NAS. NAS was calculated as the sum of scores for steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocyte ballooning (0 to 2). Therefore, it is assessed on a scale of 0-8, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Yes | 61.7 | 58.3 |
| No | 23.4 | 37.5 |
| Missing | 14.9 | 4.2 |
Improvement is defined as at least one stage decrease from baseline to week 48 in SAF score. SAF score was assessed on a scale of 0-4, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Yes | 57.4 | 50.0 |
| No | 27.7 | 45.8 |
| Missing | 14.9 | 4.2 |
Improvement is defined as at least one stage decrease from baseline to week 48 in Ishak fibrosis score. Ishak fibrosis score was assessed on a scale of 0-6, with higher scores indicating more severe disease. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Yes | 27.7 | 37.5 |
| No | 57.4 | 58.3 |
| Missing | 14.9 | 4.2 |
Change in body weight from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Kilograms | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Body Weight | -8.6 ± 7.8 | -0.8 ± 5.0 |
Relative change in body weight (measured as kg) from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| percent change | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Relative Change From Baseline in Body Weight | -8.83 ± 7.44 | -0.09 ± 7.44 |
Change in waist circumference from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| centimeters | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Waist Circumference | -6.3 ± 7.7 | 0.4 ± 6.8 |
Change in BMI from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Kilograms per meter square | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Body Mass Index (BMI) | -3.1 ± 2.8 | -0.2 ± 1.8 |
Percentage of participants with weight loss of greater than or equal to (≥) 5% of baseline body weight at 48 weeks is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Percentage of Participants With Weight Loss of >= 5% of Baseline Body Weight at Week 48 | 62.0 | 25.4 |
Percentage of participants with weight loss of ≥ 10% of baseline body weight at 48 weeks is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of participants | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Percentage of Participants With Weight Loss of >= 10% of Baseline Body Weight at Week 48 | 40.5 | 0 |
Change in HbA1c from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Percentage of HbA1C | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Glycosylated Haemoglobin A1c (HbA1c) | -1.4 ± 1.1 | 0.2 ± 1.1 |
Change in FPG from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| millimoles per liter (mmol/L) | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) | -2.20 ± 2.52 | 0.23 ± 2.94 |
Change in fasting C-peptide \[measured as nanomoles per litre (nmol/L)\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of fasting C-peptide | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Fasting C-peptide-Ratio to Baseline | 0.95 ± 47.08 | 1.00 ± 45.73 |
Change in systolic and diastolic blood pressure from baseline to week 48 is presented. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| millimeter of mercury | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Systolic Blood Pressure | -4.1 ± 17.6 | 0.1 ± 17.1 |
| Change From Baseline in Diastolic Blood Pressure | 0.4 ± 11.7 | -0.7 ± 8.4 |
Change in total cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of total cholesterol | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Total Cholesterol-Ratio to Baseline | 0.98 ± 11.86 | 1.05 ± 17.61 |
Change in LDL cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of LDL cholesterol | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Low-Density Lipoprotein (LDL) Cholesterol-Ratio to Baseline | 0.99 ± 17.88 | 1.02 ± 30.07 |
Change in HDL cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of HDL cholesterol | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol-Ratio to Baseline | 1.07 ± 12.83 | 0.99 ± 16.30 |
Change in VLDL cholesterol (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of VLDL cholesterol | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Very Low-Density Lipoprotein (VLDL) Cholesterol-Ratio to Baseline | 0.90 ± 28.37 | 1.09 ± 28.09 |
Change in triglycerides (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of triglycerides | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Triglycerides-Ratio to Baseline | 0.90 ± 28.40 | 1.09 ± 28.08 |
Change in free fatty acids (measured as mmol/L) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of FFA | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Free Fatty Acids (FFA)-Ratio to Baseline | 1.07 ± 75.99 | 1.43 ± 77.70 |
Change in hsCRP (measured as milligrams per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of hsCRP | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline | 0.63 ± 107.66 | 1.13 ± 70.38 |
Change in ALT (measured as units per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of ALT | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Alanine Aminotransferase (ALT)-Ratio to Baseline | 0.7 ± 58.1 | 1.0 ± 32.2 |
Change in AST (measured as units per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of AST | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Aspartate Aminotransferase (AST)-Ratio to Baseline | 0.7 ± 47.8 | 1.0 ± 29.0 |
Change in GGT (measured as units per liter) from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of GGT | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Gamma-Glutamyl Transferase (GGT)-Ratio to Baseline | 0.7 ± 40.9 | 1.0 ± 24.4 |
Change in albumin \[measured as grams per deciliter (g/dL)\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of albumin | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Albumin-Ratio to Baseline | 1.0 ± 6.1 | 1.0 ± 5.9 |
Change in thrombocytes \[measured as 10\^9 cells per liter\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of thrombocytes | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Changes From Baseline in Thrombocytes-Ratio to Baseline | 1.0 ± 16.1 | 1.0 ± 14.7 |
Change in INR from baseline to week 48 is presented as ratio to baseline. INR is the ratio of measured prothrombin time over normal prothrombin time and it evaluates the extrinsic coagulation pathway (vitamin K dependent clotting factors II; V, VII, IX and X). These clotting factors are synthesised in the liver, thus INR is used as a marker of liver synthesis function. The therapeutic INR range varies, most commonly an INR 2-3 goal, but ranging from 1.5-4.0. Bleeding complications are more likely to occur above an INR value of 4.0. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of INR | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in International Normalized Ratio (INR)-Ratio to Baseline | 1.02 ± 5.59 | 1.01 ± 25.07 |
Change in direct bilirubin \[measured as micromoles per liter (umol/L)\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of direct bilirubin | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Direct Bilirubin-Ratio to Baseline | 1.1 ± 33.7 | 1.0 ± 24.8 |
Change in total bilirubin \[measured as umol/L\] from baseline to week 48 is presented as ratio to baseline. Outcome measure was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (week 55); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.
| Ratio of total bilirubin | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Total Bilirubin-Ratio to Baseline | 1.0 ± 34.5 | 0.9 ± 24.5 |
An adverse event (AE) was any untoward medical occurrence in a clinical trial participant administered or using a medicinal product, whether or not considered related to the medicinal product or usage. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. Outcome measure was evaluated based on data from on-treatment period which started on the date of first administration of trial product and ended on the date of whatever comes first of: a) last dose of trial product + 49 days (7 half-lives of semaglutide), b) follow-up visit (week 55), or c) end of the in-trial period.
| Events | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Number of Treatment-Emergent Adverse Events (TEAEs) | 290 | 85 |
Hypoglycaemic episode (blood glucose less than or equal to (\<=) 3.9 mmol/L \[70 milligrams per decilitre (mg/dL)\] Or greater than (\>) 3.9 mmol/L (70 mg/dL) occurring in conjunction with hypoglycaemic symptoms) is defined as treatment emergent if the onset of the episode occurs during the on-treatment period. Outcome measure was evaluated based on data from on-treatment period which started on the date of first administration of trial product and ended on the date of whatever comes first of: a) last dose of trial product + 49 days (7 half-lives of semaglutide), b) follow-up visit (week 55), or c) end of the in-trial period.
| Episodes | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Number of Treatment-Emergent Hypoglycaemic Episodes | 34 | 15 |
Change in pulse from baseline to week 48 is presented. Outcome measure was evaluated based on data from on-treatment period which started on the date of first administration of trial product and ended on the date of whatever comes first of: a) last dose of trial product + 49 days (7 half-lives of semaglutide), b) follow-up visit (week 55), or c) end of the in-trial period.
| Beats per minute | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Change From Baseline in Pulse | 6 ± 11 | 2 ± 14 |
Collected over From week 0 to week 55. Results are based on the safety analysis set which included all participants who received at least one dose of randomised treatment.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Semaglutide 2.4 mg | 0/47 (0%) | 6/47 (12.8%) | 38/47 (80.9%) |
| Placebo | 0/24 (0%) | 2/24 (8.3%) | 15/24 (62.5%) |
| Event | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| Abdominal painGastrointestinal disorders | 0/47 | 1/24 |
| Haemorrhoidal haemorrhageGastrointestinal disorders | 0/47 | 1/24 |
| OsteoarthritisMusculoskeletal and connective tissue disorders | 0/47 | 1/24 |
| Spinal osteoarthritisMusculoskeletal and connective tissue disorders | 0/47 | 1/24 |
| Suicide attemptPsychiatric disorders | 0/47 | 1/24 |
| Calculus urinaryRenal and urinary disorders | 1/47 | 0/24 |
| CholelithiasisHepatobiliary disorders | 1/47 | 0/24 |
| HypokalaemiaMetabolism and nutrition disorders | 1/47 | 0/24 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 1/47 | 0/24 |
| Impaired gastric emptyingGastrointestinal disorders | 1/47 | 0/24 |
| Event | Semaglutide 2.4 mg | Placebo |
|---|---|---|
| NauseaGastrointestinal disorders | 21/47 | 4/24 |
| DiarrhoeaGastrointestinal disorders | 9/47 | 2/24 |
| VomitingGastrointestinal disorders | 8/47 | 0/24 |
| Urinary tract infectionInfections and infestations | 3/47 | 4/24 |
| Abdominal painGastrointestinal disorders | 6/47 | 0/24 |
| Decreased appetiteMetabolism and nutrition disorders | 6/47 | 1/24 |
| EructationGastrointestinal disorders | 6/47 | 0/24 |
| Back painMusculoskeletal and connective tissue disorders | 0/47 | 3/24 |
| Abdominal pain upperGastrointestinal disorders | 5/47 | 2/24 |
| DyspepsiaGastrointestinal disorders | 5/47 | 0/24 |
Full analysis set (FAS) included all randomized participants.
| Age, Customized(Participants) | Semaglutide 2.4 mg | Placebo | Total |
|---|---|---|---|
| <65 years | 37 | 18 | 55 |
| 65<= to <75 years | 10 | 6 | 16 |
| Sex: Female, Male(Participants) | Semaglutide 2.4 mg | Placebo | Total |
|---|---|---|---|
| Female | 31 | 18 | 49 |
| Male | 16 | 6 | 22 |
| Ethnicity (NIH/OMB)(Participants) | Semaglutide 2.4 mg | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 11 | 4 | 15 |
| Not Hispanic or Latino | 33 | 19 | 52 |
| Unknown or Not Reported | 3 | 1 | 4 |
| Race (NIH/OMB)(Participants) | Semaglutide 2.4 mg | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 1 |
| Asian | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 2 | 2 |
| White | 41 | 21 | 62 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 4 | 1 | 5 |
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Plan to share: Yes — According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Data sharing details ↗ · novonordisk-trials.com
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Studies of the drug tested here: Semaglutide
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