Investigating How CagriSema, Semaglutide and Cagrilintide Regulate Insulin Effects in the Body of People With Type 2 Diabetes
- Summary
- 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.
- Short title
- Investigating How CagriSema, Semaglutide and Cagrilintide Regulate Insulin Effects in the Body of People With Type 2 Diabetes
- Official title
- Effect of CagriSema, Semaglutide and Cagrilintide on Insulin Sensitivity and Pancreatic Endocrine Function in Adults With Type 2 Diabetes
- Control arm
- Placebo
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Completed
- Phase
- Phase 1
- Study type
- Interventional
- Completion date
- 2026-02-02
- First posted
- 2024-05-08
- Registry last updated
- 2026-02-27
- Primary completion date
- 2025-12-28
- Start date
- 2024-05-06
- Actual participants
- Participants
- Participant count basis
- Actual
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Novo Nordisk A/S
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT06403761
- ClinicalTrials.gov ID
- NCT06403761
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Parallel groups
- Purpose
- Treatment
- Masking
- Quadruple masking
- Masked roles
- Participants, Care providers, Investigators, Outcome assessors
To compare the effect of CagriSema versus placebo: Change in M-value in hyperinsulinaemic euglycaemic clamp (HEC)
Timeframe: Baseline to week 28
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.
To compare the effect of CagriSema versus semaglutide, Semaglutide versus placebo and Cagrilintide versus placebo: Change in M-value in HEC
Timeframe: Baseline to week 28
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.
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
Timeframe: Baseline to week 28
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.
Change in first-phase incremental insulin secretion rate (ISR0-8min) in hyperglycaemic clamp (HGC)
Timeframe: Baseline to week 28
Measured in picomoles per minute per square meter (pmol/min/m\^2).
Change in second-phase insulin secretion rate (ISR20-120min) in HGC
Timeframe: Baseline to week 28
Measured in pmol/min/m\^2.
Change in total insulin secretion rate (ISR0-120min) in HGC
Timeframe: Baseline to week 28
Measured in pmol/min/m\^2.
Change in insulin secretion rate at fixed glucose concentration (ISRg) in HGC
Timeframe: Baseline to week 28
Measured in pmol/min/m\^2.
Change in total insulin response (total AUC0-120 min) in HGC
Timeframe: Baseline to week 28
Measured in minute \* picomoles per liter (min\*pmol/L).
Change in insulin response to arginine (incremental insulin AUCarginine,0-10min) in HGC
Timeframe: Baseline to week 28
Measured in min\*pmol/L.
Change in C-peptide response to arginine (incremental insulin AUCarginine,0-10min) in HGC
Timeframe: Baseline to week 28
Measured in min\*nmol/L.
Change in clamp disposition index (cDI) calculated from HEC and HGC
Timeframe: Baseline to week 28
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).
Change in cDI calculated from HEC and HGC,based on lean body mass
Timeframe: Baseline to week 28
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.
Change in β-cell glucose sensitivity (insulin secretion) from HGC
Timeframe: Baseline to week 28
Measured in picomoles per minute per square meter per millimoles per liter (pmol/min/m\^2/\[mmol/L\]).
Change in β-cell glucose sensitivity from mixed meal tolerance test (MMTT) (slope of dose-response for insulin secretion vs. plasma glucose)
Timeframe: Baseline to week 28
Measured in pmol/min/m\^2/(mmol/L).
Change in glucose concentration during MMTT (total and incremental AUC0-300min)
Timeframe: Baseline to week 28
Measured in minute \* millimoles per liter (min\*mmol/L).
Change in insulin concentration during MMTT (total and incremental AUC0-300min)
Timeframe: Baseline to week 28
Measured in minute \* picomoles per liter (min\*pmol/L).
Change in C-peptide concentration during MMTT (total and incremental AUC0-300min)
Timeframe: Baseline to week 28
Measured in minute \* nanomole per liter (min\*nmol/L).
Change in glucagon concentration during MMTT (total and incremental AUC0-300min)
Timeframe: Baseline to week 28
Measured in min\*pmol/L.
Change in fasting glucose concentration (MMTT pre-meal concentrations)
Timeframe: Baseline to week 28
Measured in millimole per liter (mmol/L).
Change in fasting insulin concentration (MMTT pre-meal concentrations)
Timeframe: Baseline to week 28
Measured in picomole per milliliter (pmol/mL)
Change in fasting C-peptide concentration (MMTT pre-meal concentrations)
Timeframe: Baseline to week 28
Measured in nanomoles per liter (nmol/L).
Change in fasting glucagon concentration (MMTT pre-meal concentrations)
Timeframe: Baseline to week 28
Measured in picomoles per liter (pmol/L).
Change in fasting proinsulin concentration (MMTT pre-meal concentrations)
Timeframe: Baseline to week 28
Measured in pmol/L.
Change in HbA1c
Timeframe: Baseline to week 28
Measured as percentage points (%-points).
Change in systolic and diastolic blood pressure
Timeframe: Baseline to week 28
Measured in millimeters of mercury (mmHg).
Number of Treatment Emergent Adverse Events (TEAEs)
Timeframe: Baseline to end of study (week 34)
Count of events.
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Maximum age
- 75 Years
- Healthy volunteers
- No
- Male or female.
- Aged 18-75 years (both inclusive) at the time of signing informed consent.
- Diagnosed with type 2 diabetes greater than or equal to (>=) 180 days before screening.
- Stable daily dose(s) of metformin at effective or maximum tolerated dose, as judged by the investigator for 90 or more days before screening with or without one additional oral antidiabetic drug (OAD), except for the use of glucagon-like peptide-1 (GLP-1) receptor agonists, or sodium-glucose co-transporter-2 (SGLT-2) inhibitors in case of a high risk of cardiovascular disease (as judged by the investigator), or established cardiovascular disease, or chronic kidney disease (Glomerular Filtration Rate (eGFR) less than (<) 60 milliliter per minute per 1.73 square meter [ml/min/1.73 m^2]).
- Glycated hemoglobin (HbA1c) at screening of 6.5-9.5 percent (48-80 millimoles per mole [mmol/mol]) (both inclusive) if on metformin only, or 6.0- 9.0 percent (42-75 mmol/mol) (both inclusive) if on metformin in combination with one other OAD. A minimum of 65% of randomised participants must have HbA1c >= 7.0 % at screening.
- Body Mass index (BMI) between 25.0 and 45.0 kilogram per square meter (kg/m^2) (both inclusive) at screening.
- Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method.
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
- Renal impairment with estimated Glomerular Filtration Rate (eGFR) < 45 ml/min/1.73 m^2 at screening.
- Treatment with any medication for the indication of T2D or weight management other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days and prior insulin treatment for gestational diabetes are allowed.
- Profil Institut für Stoffwechselforschung GmbHNeuss, Germany
- 2023
- 2023-509483-20
- U1111-1300-1930
Related records
Drugs (2)
Lead sponsors (1)
Conditions (1)
- Type 2 diabetes mellitus Primary condition