A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in People With Type 2 Diabetes Treated With Once-daily Basal Insulin With or Without Metformin (REIMAGINE 3)

Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema) s.c. in Doses 2.4 mg/2.4 mg and 1.0 mg/1.0 mg Once Weekly Versus Placebo in Participants With Type 2 Diabetes as Add on to Once-daily Basal Insulin With or Without Metformin

This study will look at how much 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 "dummy" medicine (also called "placebo") that has no effect on the body. Participant will get either CagriSema or "dummy" medicine and which treatment they get is decided by chance. Participant will take the study medicine together with their current diabetes medicine (once-daily insulin with or without metformin). For each participant, the study will last for about one year.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Cagrilintide; Drug: Semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 274
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Chinese People's Liberation Army General Hospital-Endocrinology
  • Henan
    • Kaifeng, Henan, China, 475000
      • Huaihe Hospital of Henan University
    • Kaifeng, Henan, China, 475000
      • Huaihe Hospital of Henan University-Endocrinology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University_Nanjing
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University-Endocrinology
    • Zhenjiang, Jiangsu, China, 212001
      • The Affiliated Hospital of Jiangsu University-Endocrinology
  • Shandong
    • Ji'nan, Shandong, China, 250013
      • Jinan Central Hospital
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital Affiliated to Shandong University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201200
      • Shanghai Pudong New Area People's Hospital-Endocrinology
• Japan
  • Arakawa-ku, Tokyo, Japan, 116-0012
    • Kumanomae Nishimura Naika Clinic_Internal Medicine
  • Chiba-shi, Chiba, Japan, 260-0804
    • Akaicho Clinic
  • Fukuoka-shi, Fukuoka, Japan, 819-0168
    • Kunisaki Makoto Clinic
  • Fukuoka-shi, Fukuoka, Japan, 819-0006
    • Futata Tetsuhiro Clinic Meinohama_Internal medicine
  • Hokkaido, Japan, 062-0007
    • Sasaki Internal Medicine
  • Ibaraki, Japan, 311-0113
    • Naka Kinen Clinic_Internal medicine
  • Kanagawa, Japan, 235-0045
    • H.E.C Science Clinic
  • Kyoto-shi, Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Mito-shi, Ibaraki, Japan, 311-4153
    • Minami Akatsuka Clinic
  • Tokyo, Japan, 103-0027
    • Tokyo-Eki Center-building Clinic
  • Tokyo, Japan, 103-0027
    • Tokyo-Eki Center-building Clinic_Internal Medicine
  • Tokyo, Japan, 104-0031
    • Fukuwa Clinic_Internal Medicine
  • Tokyo, Japan, 125-0054
    • Kato Clinic of Internal Medicine_Internal Medicine
  • Hokkaido, Japan
    • Sapporo-shi, Hokkaido, Hokkaido, Japan, Japan, 060-0062
      • Manda Memorial Hospital_Internal Medicine
  • Kanagawa
    • Yamato-shi, Kanagawa, Japan, 242-0004
      • Tsuruma Kaneshiro Diabetes Clinic
• Serbia
  • Zaječar, Serbia, 19000
    • Policlinic for diabetes
  • RS
    • Belgrade, RS, Serbia, 11050
      • Healthcare centre Zvezdara
    • Kragujevac, RS, Serbia, 34000
      • Healthcare centre Kragujevac
    • Niš, RS, Serbia, 18 000
      • University Clinical Centre Nis
    • Niš, RS, Serbia, 18000
      • Healthcare centre Nis
• Slovakia
  • Kráľovský Chlmec, Slovakia, 077 01
    • MOMED, s.r.o
  • Levice, Slovakia, 93401
    • DIA - KONTROL s.r.o.
  • Malacky, Slovakia, 901 01
    • SIN AZUCAR s.r.o.
  • Rimavská Sobota, Slovakia, 979 01
    • ENRIN, s.r.o.
  • Spišská Nová Ves, Slovakia, 05201
    • LUDIA, s. r. o.
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Oraderumaz (Pty) Ltd
  • Gauteng
    • Lenasia, Gauteng, South Africa, 1827
      • Lenasia Clinical Trial Centre
    • Pretoria, Gauteng, South Africa, 0186
      • Clinical Trial Systems (CTC)
    • Pretoria, Gauteng, South Africa, 0002
      • Prinshof Medical Campus
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7760
      • Ashmed Medi-Centre
• United States
  • California
    • Northridge, California, United States, 91325
      • Valley Clinical Trials, Inc.
  • Florida
    • Miami, Florida, United States, 33155
      • Bioclinical Research Alliance
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Iowa Diab & Endo Res Center
  • Kansas
    • Newton, Kansas, United States, 67114
      • Alliance for Multispec Res
  • Michigan
    • Flint, Michigan, United States, 48532
      • Elite Research Center
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Palm Research Center Inc.
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27614
      • University of North Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Res-Dallas
    • Houston, Texas, United States, 77079
      • PlanIt Research, PLLC
    • Houston, Texas, United States, 77061
      • Synergy Groups Medical
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center
    • Newport News, Virginia, United States, 23606
      • TPMG Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 mellitus ≥180 days before screening.
• On stable once-daily dose of basal insulin (minimum of 0.25 units per kilogram per day (U/kg/day) or 20 U/day) alone or in combination with metformin (at effective or maximum tolerated dose as judged by the investigator) for 90 days prior to screening.
• Glycated haemoglobin (HbA1c) 7.0-10.5 percent (53-91 millimoles per mole [mmol/mol]) (both inclusive) as determined by central laboratory at screening.
• Body Mass Index (BMI) greater than or equal to 25 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 (eGFR) less than 30 milliliters 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.
• 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.
• Known hypoglycaemia unawareness as indicated by the investigator according to Clarke's questionnaire question 8.
• Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: CagriSema Dose 1; Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) at escalating doses every week in 8-week dose escalation period until target dose (dose 1) of CagriSema (cagrilintide and semaglutide) is achieved and maintained up to 32 weeks.	Drug: Cagrilintide; Participants will receive once-weekly cagrilintide subcutaneously.; Drug: Semaglutide; Participants will receive once-weekly semaglutide subcutaneously.
Active Comparator: CagriSema Dose 2; Participants will receive once-weekly s.c injections of CagriSema (cagrilintide and semaglutide) at escalating doses every week in 16-week dose escalation period until target dose (dose 2) of CagriSema(cagrilintide and semaglutide) is achieved and maintained up to 24 weeks.	Drug: Cagrilintide; Participants will receive once-weekly cagrilintide subcutaneously.; Drug: Semaglutide; Participants will receive once-weekly semaglutide subcutaneously.
Placebo Comparator: Placebo Dose 1; Participants will receive once-weekly s.c injection of placebo matched to cagrisema dose 1 (cagrilintide and semaglutide) for 40 weeks.	Drug: Placebo; Participants will receive placebo matched to cagrilintide and semaglutide subcutaneously.
Placebo Comparator: Placebo Dose 2; Participants will receive once-weekly s.c injection of placebo matched to cagrisema dose 2 (cagrilintide and semaglutide) for 40 weeks	Drug: Placebo; Participants will receive placebo matched to cagrilintide and semaglutide subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycated Haemoglobin (HbA1c)	Measured in percentage (%)- points.	From baseline (week 0) to end of treatment (week 40)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Adverse Events (TEAEs)	Measured as count of events.	From baseline (week 0) to end of treatment +7 weeks (week 47)
Relative Change in Body Weight	Measured in percentage (%).	From baseline (week 0) to end of treatment (week 40)
Number of Participants Who Achieve Greater than or Equal to (≥) 10% Body Weight Reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Number of Participants Who Achieve ≥15% Body Weight Reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Number of Participants Who Achieve HbA1c Target Values of Less than (<) 7.0% (<53 millimole per mole [mmol/mol])	Measured as count of participants.	At end of treatment (week 40)
Number of Participants Who Achieve HbA1c Target Values of Less than or Equal to (≤) 6.5% (≤48 mmol/mol)	Measured as count of participants.	At end of treatment (week 40)
Change in Fasting Plasma Glucose (FPG)	Measured as millimole per liter (mmol/L).	From baseline (week 0) to end of treatment (week 40)
Change in Insulin Dose	Measured in units (u).	From baseline (week 0) to end of treatment (week 40)
Number of Participants Who Achieve Insulin Dose Equal to (=) 0 Units	Measured as count of participants.	At end of treatment (week 40)
Change in 7-point Self-measured Plasma Glucose (SMPG) Profiles: Mean 7-point profile and Mean postprandial increment (over all meals)	Measured in mmol/L.	From baseline (week 0) to end of treatment (week 40)
Number of Participants Who Achieve ≥5% Body Weight Reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Number of Participants Who Achieve ≥20% Body Weight Reduction	Measured as count of participants.	From baseline (week 0) to end of treatment (week 40)
Change in Waist Circumference	Measured in centimeter (cm).	From baseline (week 0) to end of treatment (week 40)
Change in Systolic Blood Pressure (SBP)	Measured in millimeter of mercury (mmHg).	From baseline (week 0) to end of treatment (week 40)
Change in Diastolic Blood Pressure (DBP)	Measured in mmHg.	From baseline (week 0) to end of treatment (week 40)
Ratio to Baseline in High Sensitivity C-reactive Protein (hsCRP)	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to Baseline in Lipids: Non-high Density Lipoprotein (Non-HDL) Cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to Baseline in Lipids: Triglycerides	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to Baseline in Lipids: Low-Density Lipoprotein (LDL) Cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to Baseline in Lipids: Very Low-Density Lipoprotein (VLDL) cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to Baseline in Lipids: HDL Cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to Baseline in Lipids: Total Cholesterol	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to Baseline in Lipids: Free Fatty Acids	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Change in Short Form-36 Version 2.0 Health Survey (SF-36v2): Vitality score	Measured as score points. SF-36v2 Acute measures Health-Related Quality of Life (HRQoL). The measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 Acute scores are norm-based scores, that is. transformed to a scale where the 2009 US general population has a mean of 50 and a standard deviation of 10. Higher scores indicate better functional health and well-being. The vitality score range is from 25.6 to 69.1.	From baseline (week 0) to end of treatment (week 40)
Change in SF-36v2: Physical Component Summary Score	Measured as score points. SF-36v2 Acute measures HRQoL. The measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 Acute scores are norm-based scores, that is. transformed to a scale where the 2009 US general population has a mean of 50 and a standard deviation of 10. Higher scores indicate better functional health and well-being. The score range for physical component summary is 6.1 to 79.7.	From baseline (week 0) to end of treatment (week 40)
Change in SF-36v2: Mental Component Summary Core	Measured as score points. SF-36v2 Acute measures HRQoL. The measure consists of 36 items yielding 8 health domain scores and 2 component summary scores. SF-36v2 Acute scores are norm-based scores, that is. transformed to a scale where the 2009 US general population has a mean of 50 and a standard deviation of 10. Higher scores indicate better functional health and well-being. The score range for mental component summary score is -3.8 to 78.7.	From baseline (week 0) to end of treatment (week 40)
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score	Measured as score points. DTSQs measures treatment satisfaction and diabetes-specific quality of life. The measure consists of 8 items yielding 1 global score and 2 single item scores. Higher scores on the global score indicate greater satisfaction with treatment. Lower scores on the single-item scores indicate BG levels closer to the ideal, while higher scores indicate problems. Single-item scores (score range): Perceived frequency of hyperglycaemia (0-6), Perceived frequency of hypoglycaemia (0-6). Global score (score range): Total Treatment Satisfaction (0-36).	From baseline (week 0) to end of treatment (week 40)
Number of Clinically Significant Hypoglycaemic Episodes (level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by Blood Glucose Meter)	Measured as count of episodes.	From baseline (week 0) to end of treatment +7 weeks (week 47)
Number of Clinically Significant Hypoglycaemic Episodes (level 3)	Measured as count of episodes. Hypoglycaemic episodes (level 3) is hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold.	From baseline (week 0) to end of treatment +7 weeks (week 47)
Ratio to Baseline in Leptin	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)
Ratio to Baseline in Soluble Leptin Receptor	Measured in ratio.	From baseline (week 0) to end of treatment (week 40)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2024
• Primary Completion (Actual): September 9, 2025
• Study Completion (Actual): October 23, 2025

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 21, 2024

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Substandard Drugs; Pharmaceutical Preparations; semaglutide; cagrilintide
• Other Study ID Numbers: NN9388-7637; U1111-1283-0754 (Other Identifier: World Health Organization (WHO)); 2022-502679-43 (Other Identifier: European Medical Agency (EMA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No