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

NCT06403761 | Completed Phase 1

• 3 other identifiers: NN9388-7782U1111-1300-19302023-509483-20
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (25)

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

  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

  Baseline to week 28

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

  Baseline to week 28

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

  Baseline to week 28

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

  Baseline to week 28

Study Arms (4)

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.

Drug: Semaglutide; Drug: Cagrilintide; Drug: Placebo semaglutide; Drug: Placebo cagrilintide

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.

Drug: Semaglutide; Drug: Placebo semaglutide

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.

Drug: Cagrilintide; Drug: Placebo cagrilintide

Placebo

PLACEBO COMPARATOR

Participants will receive once-weekly s.c injection of placebo matched to semaglutide and cagrilintide for 28 weeks.

Drug: Placebo semaglutide; Drug: Placebo cagrilintide

Interventions

Cagrilintide DRUG

Participants will receive once-weekly cagrilintide subcutaneously.

CagriSema; Cagrilintide

Placebo semaglutide DRUG

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

CagriSema; Placebo; Semaglutide

Placebo cagrilintide DRUG

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

CagriSema; Cagrilintide; Placebo

Semaglutide DRUG

Participants will receive once-weekly semaglutide subcutaneously.

CagriSema; Semaglutide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (1)

Profil Institut für Stoffwechselforschung GmbH

Neuss, 41460, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

semaglutide; cagrilintide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2024
• First Posted: May 8, 2024
• Study Start: May 6, 2024
• Primary Completion: December 28, 2025
• Study Completion: February 2, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)