A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Tirzepatide in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor

Phase 3

Active, not recruiting

• Conditions: Type 2 Diabetes
• Interventions: Drug: Cagrilintide; Drug: Tirzepatide; Drug: Semaglutide

• Registration Number: NCT06221969
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

This study will look at how well CagriSema helps people with type 2 diabetes lower their blood sugar and body weight. CagriSema is a new investigational medicine. Doctors may not yet prescribe CagriSema. CagriSema will be compared to a medicine called tirzepatide that doctors may prescribe in some countries. Participants will get either CagriSema or tirzepatide. Which treatment participant get is decided by chance like flipping a coin. Participant will have an equal chance of receiving either drug. For each participant, the study will last for up to one and a half years.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-01-15
• Study First Submitted QC: 2024-01-15
• Study Start: 2024-01-16
• Study First Posted: 2024-01-24
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-08
• Last Update Posted: 2025-09-09
• Primary Completion: 2026-02-20
• Study Completion: 2026-04-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• Male or female (sex at birth).
• Age 18 years or above at the time of signing the informed consent.
• Diagnosed with type 2 diabetes ≥ 180 days before screening.
• Stable daily dose(s) ≥ 90 days before screening of any of the following antidiabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose as judged by the investigator: metformin with or without an sodium-glucose co-transporter-2 (SGLT2) inhibitor.
• HbA1c 7.0-10.5% (53-91 mmol/mol) (both inclusive) as determined by central laboratory at screening.
• Body mass index (BMI) of ≥ 30.0 kilogram per square meter (kg/m^2) at screening. BMI will be calculated in the electronic case report form (eCRF) based on height and body weight at screening.

Exclusion Criteria

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective contraceptive method.
• Renal impairment with estimated Glomerular Filtration Rate < 30 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) as determined by central laboratory at screening.
• Treatment with any medication for the indication of diabetes or obesity 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.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by an eye 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CagriSema	Cagrilintide	Participants will receive cagrilintide dose 1 and semaglutide dose 2 subcutaneously once-weekly (dose escalation period of 16 weeks) for up to 68 weeks.
CagriSema	Semaglutide	Participants will receive cagrilintide dose 1 and semaglutide dose 2 subcutaneously once-weekly (dose escalation period of 16 weeks) for up to 68 weeks.
Tirzepatide	Tirzepatide	Participants will receive tirzepatide dose 1 subcutaneously once-weekly (dose escalation period of 20 weeks) for up to 68 weeks.

Primary Outcome Measures

Name	Time	Method
Relative change in body weight	From baseline (week 0) to end of treatment (week 68)	Measured in percentage (%).
Change in glycated haemoglobin (HbA1c)	From baseline (week 0) to end of treatment (week 68)	Measured in percentage (%)-points.

Secondary Outcome Measures

Name	Time	Method
Change in HbA1c	From baseline (week 0) to end of treatment (week 68)	Measured in %-points.
Achievement of ≥ 15 % weight reduction	From baseline (week 0) to end of treatment (week 68)	Count of participant
Change in systolic blood pressure	From baseline (week 0) to end of treatment (week 68)	Measured in millimeters of mercury(mmHg).
Change in waist circumference	From baseline (week 0) to end of treatment (week 68)	Measured in centimeter (cm).
Ratio to baseline in lipids: Low-density lipoprotein (LDL) cholesterol	From baseline (week 0) to end of treatment (week 68)	Measured in ratio.
Change in fasting plasma glucose (FPG)	From baseline (week 0) to end of treatment (week 68)	Measured in millimoles per liter (mmol/L).
Achievement of HbA1c target values of less than (<) 7.0% (<53 millimole per mole [mmol/mol])	At end of treatment (week 68)	Count of participant
Achievement of HbA1c target values of less than or equal to (≤) 6.5% (≤ 48 mmol/mol)	From baseline (week 0) to end of treatment (week 68)	Count of participant
Achievement of greater than or equal to (≥) 5% weight reduction	From baseline (week 0) to end of treatment (week 68)	Count of participant
Change in diastolic blood pressure	From baseline (week 0) to end of treatment (week 68)	Measured in mmHg.
Ratio to baseline in lipids: Very low-density lipoprotein (VLDL) cholesterol	From baseline (week 0) to end of treatment (week 68)	Measured in ratio.
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (<54 milligram per deciliter [mg/dL]), confirmed by blood glucose meter)	From baseline (week 0) to end of study (week 74)	Count of episodes
Achievement of ≥ 10% weight reduction	From baseline (week 0) to end of treatment (week 68)	Count of participant
Achievement of ≥ 20 % weight reduction	From baseline (week 0) to end of treatment (week 68)	Count of participant
Ratio to baseline in lipids: Total cholesterol	From baseline (week 0) to end of treatment (week 68)	Measured in ratio.
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey	From baseline (week 0) to end of treatment (week 68)	The SF-36 v2 will be used to measure differences in quality of life and mental wellbeing. The scores 0-100 (where higher scores indicated a better quality of life and mental wellbeing) from the SF-36 will be converted to a norm-based score using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 1998 United States general population. Measured as score on a scale.
Ratio to baseline in lipids: Triglycerides	From baseline (week 0) to end of treatment (week 68)	Measured in ratio.
Number of Treatment-emergent Adverse Events (TEAEs)	From baseline (week 0) to end of study (week 74)	Count of events
Ratio to baseline in lipids: High-density lipoprotein (HDL) cholesterol	From baseline (week 0) to end of treatment (week 68)	Measured in ratio.
Ratio to baseline in lipids: non-HDL cholesterol	From baseline (week 0) to end of treatment (week 68)	Measured in ratio.
Change in Impact of Weight on Quality of Life-Lite Clinical Trials (IWQOL-Lite-CT) version 3	From baseline (week 0) to end of treatment (week 68)	IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Higher scores indicate better levels of functioning. Composite scores (score range): Physical composite (0-100), Psychosocial composite (0-100), Physical Function composite (0-100). Total score (0-100). Higher scores indicate better level of functioning.
Number of severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold	From baseline (week 0) to end of study (week 74)	Count of episodes

Trial Locations

Locations (171)

Univ of Alabama_Birmingham; 🇺🇸 Birmingham, Alabama, United States

Prime Medical Group, LLC; 🇺🇸 Gilbert, Arizona, United States

Velocity Clinical Research-Phoenix; 🇺🇸 Phoenix, Arizona, United States

Synexus Rsch /Cnt Phnx Med C; 🇺🇸 Phoenix, Arizona, United States

Arkansas Clinical Research; 🇺🇸 Little Rock, Arkansas, United States

Unity Health-Searcy Medical Center; 🇺🇸 Searcy, Arkansas, United States

Velocity Clin Res-Chula Vista; 🇺🇸 Chula Vista, California, United States

Headlands Research California, LLC; 🇺🇸 Escondido, California, United States

Neighborhood Healthcare; 🇺🇸 Escondido, California, United States

St. Jude Heritage Yorba Linda - Pediatric Ste D; 🇺🇸 Fullerton, California, United States

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