Investigating How CagriSema, Semaglutide and Cagrilintide Regulate Insulin Effects in the Body of People With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Effect of CagriSema, Semaglutide and Cagrilintide on Insulin Sensitivity and Pancreatic Endocrine Function in Adults With Type 2 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06403761
• Other study ID #: NN9388-7782
• Secondary ID: U1111-1300-19302
• Status: Recruiting
• Phase: Phase 1
• Start date: May 6, 2024
• Est. completion date: December 18, 2025

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 18, 2025
• Est. primary completion date: October 26, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Semaglutide
Participants will receive once-weekly semaglutide subcutaneously.
• Cagrilintide
Participants will receive once-weekly cagrilintide subcutaneously.
• Placebo semaglutide
Participants will receive once-weekly placebo matched to semaglutide subcutaneously.
• Placebo cagrilintide
Participants will receive once-weekly placebo matched to cagrilintide subcutaneously.

Locations

Country	Name	City	State
Germany	Profil Institut für Stoffwechselforschung GmbH	Neuss

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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
Secondary	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
Secondary	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
Secondary	Change in second-phase insulin secretion rate (ISR20-120min) in HGC	Measured in pmol/min/m^2.	Baseline to week 28
Secondary	Change in total insulin secretion rate (ISR0-120min) in HGC	Measured in pmol/min/m^2.	Baseline to week 28
Secondary	Change in insulin secretion rate at fixed glucose concentration (ISRg) in HGC	Measured in pmol/min/m^2.	Baseline to week 28
Secondary	Change in total insulin response (total AUC0-120 min) in HGC	Measured in minute * picomoles per liter (min*pmol/L).	Baseline to week 28
Secondary	Change in insulin response to arginine (incremental insulin AUCarginine,0-10min) in HGC	Measured in min*pmol/L.	Baseline to week 28
Secondary	Change in C-peptide response to arginine (incremental insulin AUCarginine,0-10min) in HGC	Measured in min*nmol/L.	Baseline to week 28
Secondary	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
Secondary	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
Secondary	Change in ß-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
Secondary	Change in ß-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
Secondary	Change in glucose concentration during MMTT (total and incremental AUC0-300min)	Measured in minute * millimoles per liter (min*mmol/L).	Baseline to week 28
Secondary	Change in insulin concentration during MMTT (total and incremental AUC0-300min)	Measured in minute * picomoles per liter (min*pmol/L).	Baseline to week 28
Secondary	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
Secondary	Change in glucagon concentration during MMTT (total and incremental AUC0-300min)	Measured in min*pmol/L.	Baseline to week 28
Secondary	Change in fasting glucose concentration (MMTT pre-meal concentrations)	Measured in millimole per liter (mmol/L).	Baseline to week 28
Secondary	Change in fasting insulin concentration (MMTT pre-meal concentrations)	Measured in picomole per milliliter (pmol/mL)	Baseline to week 28
Secondary	Change in fasting C-peptide concentration (MMTT pre-meal concentrations)	Measured in nanomoles per liter (nmol/L).	Baseline to week 28
Secondary	Change in fasting glucagon concentration (MMTT pre-meal concentrations)	Measured in picomoles per liter (pmol/L).	Baseline to week 28
Secondary	Change in fasting proinsulin concentration (MMTT pre-meal concentrations)	Measured in pmol/L.	Baseline to week 28
Secondary	Change in HbA1c	Measured as percentage points (%-points).	Baseline to week 28
Secondary	Change in systolic and diastolic blood pressure	Measured in millimeters of mercury (mmHg).	Baseline to week 28
Secondary	Number of Treatment Emergent Adverse Events (TEAEs)	Count of events.	Baseline to end of study (week 34)