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Completed

NCT Number: NCT06403761

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

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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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Profil Institut für Stoffwechselforschung GmbH

Neuss, 41460, Germany

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

semaglutide

Drug

Participants will receive once-weekly semaglutide subcutaneously.

Cagrilintide

Drug

Participants will receive once-weekly cagrilintide subcutaneously.

Placebo Semaglutide

Drug

Participants will receive once-weekly placebo matched to semaglutide subcutaneously.

Placebo Cagrilintide

Drug

Participants will receive once-weekly placebo matched to cagrilintide subcutaneously.

Primary outcomes

  1. To compare the effect of CagriSema versus placebo: Change in M-value in hyperinsulinaemic euglycaemic clamp (HEC)

    Time frame: 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.

Secondary outcomes

  1. To compare the effect of CagriSema versus semaglutide, Semaglutide versus placebo and Cagrilintide versus placebo: Change in M-value in HEC

    Time frame: 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.

  2. 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

    Time frame: 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.

  3. Change in first-phase incremental insulin secretion rate (ISR0-8min) in hyperglycaemic clamp (HGC)

    Time frame: Baseline to week 28

    Measured in picomoles per minute per square meter (pmol/min/m^2).

  4. Change in second-phase insulin secretion rate (ISR20-120min) in HGC

    Time frame: Baseline to week 28

    Measured in pmol/min/m^2.

  5. Change in total insulin secretion rate (ISR0-120min) in HGC

    Time frame: Baseline to week 28

    Measured in pmol/min/m^2.

  6. Change in insulin secretion rate at fixed glucose concentration (ISRg) in HGC

    Time frame: Baseline to week 28

    Measured in pmol/min/m^2.

  7. Change in total insulin response (total AUC0-120 min) in HGC

    Time frame: Baseline to week 28

    Measured in minute * picomoles per liter (min*pmol/L).

  8. Change in insulin response to arginine (incremental insulin AUCarginine,0-10min) in HGC

    Time frame: Baseline to week 28

    Measured in min*pmol/L.

  9. Change in C-peptide response to arginine (incremental insulin AUCarginine,0-10min) in HGC

    Time frame: Baseline to week 28

    Measured in min*nmol/L.

  10. Change in clamp disposition index (cDI) calculated from HEC and HGC

    Time frame: 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).

  11. Change in cDI calculated from HEC and HGC,based on lean body mass

    Time frame: 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.

  12. Change in β-cell glucose sensitivity (insulin secretion) from HGC

    Time frame: Baseline to week 28

    Measured in picomoles per minute per square meter per millimoles per liter (pmol/min/m^2/[mmol/L]).

  13. Change in β-cell glucose sensitivity from mixed meal tolerance test (MMTT) (slope of dose-response for insulin secretion vs. plasma glucose)

    Time frame: Baseline to week 28

    Measured in pmol/min/m^2/(mmol/L).

  14. Change in glucose concentration during MMTT (total and incremental AUC0-300min)

    Time frame: Baseline to week 28

    Measured in minute * millimoles per liter (min*mmol/L).

  15. Change in insulin concentration during MMTT (total and incremental AUC0-300min)

    Time frame: Baseline to week 28

    Measured in minute * picomoles per liter (min*pmol/L).

  16. Change in C-peptide concentration during MMTT (total and incremental AUC0-300min)

    Time frame: Baseline to week 28

    Measured in minute * nanomole per liter (min*nmol/L).

  17. Change in glucagon concentration during MMTT (total and incremental AUC0-300min)

    Time frame: Baseline to week 28

    Measured in min*pmol/L.

  18. Change in fasting glucose concentration (MMTT pre-meal concentrations)

    Time frame: Baseline to week 28

    Measured in millimole per liter (mmol/L).

  19. Change in fasting insulin concentration (MMTT pre-meal concentrations)

    Time frame: Baseline to week 28

    Measured in picomole per milliliter (pmol/mL)

  20. Change in fasting C-peptide concentration (MMTT pre-meal concentrations)

    Time frame: Baseline to week 28

    Measured in nanomoles per liter (nmol/L).

  21. Change in fasting glucagon concentration (MMTT pre-meal concentrations)

    Time frame: Baseline to week 28

    Measured in picomoles per liter (pmol/L).

  22. Change in fasting proinsulin concentration (MMTT pre-meal concentrations)

    Time frame: Baseline to week 28

    Measured in pmol/L.

  23. Change in HbA1c

    Time frame: Baseline to week 28

    Measured as percentage points (%-points).

  24. Change in systolic and diastolic blood pressure

    Time frame: Baseline to week 28

    Measured in millimeters of mercury (mmHg).

  25. Number of Treatment Emergent Adverse Events (TEAEs)

    Time frame: Baseline to end of study (week 34)

    Count of events.

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2025
Study completion
2026
First posted
May 8, 2024
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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