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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1300-1930 | Other Identifier | World Health Organization (WHO) | |
| 2023-509483-20 | Other Identifier | European Medical Agency (EMA) |
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This study will look at how CagriSema, semaglutide and cagrilintide regulate insulin effects in the body of people with type 2 diabetes (T2D). CagriSema is a new investigational medicine that combines two medicines called cagrilintide and semaglutide. Doctors may not yet prescribe CagriSema. Participants will either get CagriSema, semaglutide, cagrilintide, or a ''dummy'' medicine. Which treatment the participants will get is decided by chance. Participants will get the study medicine together with the current daily diabetes medicine metformin. Participants should not take other medicines for diabetes during the study. The study will last for about 42 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CagriSema | Experimental | Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks. |
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| Semaglutide | Experimental | Participants will receive once-weekly s.c injections of semaglutide at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks. |
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| Cagrilintide | Experimental | Participants will receive once-weekly s.c injections of cagrilintide at escalating doses every 4 weeks in a 16-week dose escalation period until target dose of CagriSema is achieved and maintained for 12 weeks. |
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| Placebo | Placebo Comparator | Participants will receive once-weekly s.c injection of placebo matched to semaglutide and cagrilintide for 28 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Semaglutide | Drug | Participants will receive once-weekly semaglutide subcutaneously. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Transparency (dept. 2834) | Novo Nordisk A/S | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Profil Institut für Stoffwechselforschung GmbH | Neuss | 41460 | Germany |
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com.
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| Cagrilintide | Drug | Participants will receive once-weekly cagrilintide subcutaneously. |
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| Placebo semaglutide | Drug | Participants will receive once-weekly placebo matched to semaglutide subcutaneously. |
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| Placebo cagrilintide | Drug | Participants will receive once-weekly placebo matched to cagrilintide subcutaneously. |
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| 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) |
| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C000591245 | semaglutide |
| C000717792 | cagrilintide |
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