| Outcome Measures: |
Primary: To compare the effect of CagriSema versus placebo: Change in M-value in hyperinsulinaemic euglycaemic clamp (HEC), M-value from the HEC is calculated from glucose infusion rate (GIR) over the last 30 minutes of the clamp, corresponding to steady state. M-value is defined as: (GIR150-180 min normalised by body weight \[milligram per minute per kilogram {mg/min/kg}\]). Measured in mg/min/kg., Baseline to week 28 | Secondary: To compare the effect of CagriSema versus semaglutide, Semaglutide versus placebo and Cagrilintide versus placebo: Change in M-value in HEC, M-value from the HEC is calculated from GIR over the last 30 minutes of the clamp, corresponding to steady state. M-value is defined as: (GIR150-180 min normalised by body weight \[mg/min/kg\]). Measured in mg/min/kg., Baseline to week 28|To compare the effect of CagriSema versus placebo, CagriSema versus semaglutide, Semaglutide versus placebo and Cagrilintide versus placebo: Change in M-value in HEC, normalised by lean body mass, M-value from the HEC is calculated from GIR over the last 30 minutes of the clamp, corresponding to steady state. M-value is defined as: (GIR150-180 min normalised by body weight \[mg/min/kg\]). Measured in mg/min/kg., Baseline to week 28|Change in first-phase incremental insulin secretion rate (ISR0-8min) in hyperglycaemic clamp (HGC), Measured in picomoles per minute per square meter (pmol/min/m\^2)., Baseline to week 28|Change in second-phase insulin secretion rate (ISR20-120min) in HGC, Measured in pmol/min/m\^2., Baseline to week 28|Change in total insulin secretion rate (ISR0-120min) in HGC, Measured in pmol/min/m\^2., Baseline to week 28|Change in insulin secretion rate at fixed glucose concentration (ISRg) in HGC, Measured in pmol/min/m\^2., Baseline to week 28|Change in total insulin response (total AUC0-120 min) in HGC, Measured in minute \* picomoles per liter (min\*pmol/L)., Baseline to week 28|Change in insulin response to arginine (incremental insulin AUCarginine,0-10min) in HGC, Measured in min\*pmol/L., Baseline to week 28|Change in C-peptide response to arginine (incremental insulin AUCarginine,0-10min) in HGC, Measured in min\*nmol/L., Baseline to week 28|Change in clamp disposition index (cDI) calculated from HEC and HGC, cDI is defined as the product of the M-value derived from the hyperinsulinemic euglycemic clamp over the last 30 minutes and total insulin secretion (ISR AUC0-120min) derived from the insulin secretion rate based on C-peptide using the using the deconvolution technique divided by the total glucose AUC0-120min from the hyperglycemic clamp portion of the study. Measured in picomoles \* liter per square meter per square minute per kilogram (pmol\*L/m\^2/min\^2/kg)., Baseline to week 28|Change in cDI calculated from HEC and HGC,based on lean body mass, cDI is defined as the product of the M-value derived from the hyperinsulinemic euglycemic clamp over the last 30 minutes and total insulin secretion (ISR AUC0-120min) derived from the insulin secretion rate based on C-peptide using the using the deconvolution technique divided by the total glucose AUC0-120min from the hyperglycemic clamp portion of the study. Measured in pmol\*L/m\^2/min\^2/kg., Baseline to week 28|Change in β-cell glucose sensitivity (insulin secretion) from HGC, Measured in picomoles per minute per square meter per millimoles per liter (pmol/min/m\^2/\[mmol/L\])., Baseline to week 28|Change in β-cell glucose sensitivity from mixed meal tolerance test (MMTT) (slope of dose-response for insulin secretion vs. plasma glucose), Measured in pmol/min/m\^2/(mmol/L)., Baseline to week 28|Change in glucose concentration during MMTT (total and incremental AUC0-300min), Measured in minute \* millimoles per liter (min\*mmol/L)., Baseline to week 28|Change in insulin concentration during MMTT (total and incremental AUC0-300min), Measured in minute \* picomoles per liter (min\*pmol/L)., Baseline to week 28|Change in C-peptide concentration during MMTT (total and incremental AUC0-300min), Measured in minute \* nanomole per liter (min\*nmol/L)., Baseline to week 28|Change in glucagon concentration during MMTT (total and incremental AUC0-300min), Measured in min\*pmol/L., Baseline to week 28|Change in fasting glucose concentration (MMTT pre-meal concentrations), Measured in millimole per liter (mmol/L)., Baseline to week 28|Change in fasting insulin concentration (MMTT pre-meal concentrations), Measured in picomole per milliliter (pmol/mL), Baseline to week 28|Change in fasting C-peptide concentration (MMTT pre-meal concentrations), Measured in nanomoles per liter (nmol/L)., Baseline to week 28|Change in fasting glucagon concentration (MMTT pre-meal concentrations), Measured in picomoles per liter (pmol/L)., Baseline to week 28|Change in fasting proinsulin concentration (MMTT pre-meal concentrations), Measured in pmol/L., Baseline to week 28|Change in HbA1c, Measured as percentage points (%-points)., Baseline to week 28|Change in systolic and diastolic blood pressure, Measured in millimeters of mercury (mmHg)., Baseline to week 28|Number of Treatment Emergent Adverse Events (TEAEs), Count of events., Baseline to end of study (week 34)
|
