A Research Study to Look Into the Long-term Effect on Weight Loss of CagriSema in People With Obesity

Long-term Efficacy and Safety of Cagrilintide s.c. 2.4 mg in Combination With Semaglutide s.c. 2.4 mg (CagriSema 2.4 mg/2.4 mg) Once Weekly Versus Placebo in Participants With Obesity

This study will look at how well CagriSema helps people with obesity lose weight compared to a "dummy medicine". CagriSema is a new medicine developed by Novo Nordisk. CagriSema cannot yet be prescribed by doctors. The study has two parts: First part is called the main phase and will last for 2 years, and second part is called the extension phase and will last for 1 year. In the main phase participants will either get CagriSema or "dummy medicine". Which treatment participants get is decided by chance and is not known by participants or the study doctor. In the extension phase participants will get either CagriSema or slowly reduce participants dose of CagriSema if participants had CagriSema in the main phase. Which treatment participants get is decided by chance and is not known by participants or the study doctor in both phases. If participants had "dummy medicine" in the main phase, participants will get CagriSema in the extension phase. Like all medicines, the study medicine may have side effects.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo cagrilintide; Drug: Placebo semaglutide; Drug: Semaglutide; Drug: Cagrilintide

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc - Serv Endocrinologie - Diabétologie
  • Edegem, Belgium, 2650
    • UZA - UZ Antwerpen - Department of Endocrinology
  • Leuven, Belgium, 3000
    • UZ Leuven - Endocrinology
  • Mons, Belgium, 7000
    • CHU Helora - Hôpital de Mons - Site Constantinople
• Canada
  • Québec, Canada, G2J 0C4
    • Alpha Recherche Clinique - Lebourgneuf
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 4A1
      • Dr. M.B. Jones Inc
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Nova Scotia Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8L 5G4
      • Premier Clinical Trial Research Network (PCTRN)
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus Universitetshospital, Steno Diabetes Center Aarhus
  • Esbjerg, Denmark, 6700
    • Sydvestjysk Sygehus Esbjerg - Medicinsk Endokrinologisk Ambulatorium, Forskningsenheden
  • Hellerup, Denmark, 2900
    • Gentofte Hospital - Center for Klinisk Metabolisk Forskning
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital Endokrinologisk forsknings afsnit 159
  • Køge, Denmark, 4600
    • Sjællands Universitetshospital, Køge - Medicinsk Afdeling
• Portugal
  • Lisbon, Portugal, 1998-018
    • CUF Descobertas
  • Lisbon, Portugal, 1250-189
    • APDP - Associação Protectora dos Diabéticos de Portugal
  • Lisbon, Portugal, 1998-018
    • Hospital Cuf Descobertas S.A.
  • Porto, Portugal, 4200-319
    • Unidade Local de Saude de Sao Joao E.P.E
  • Vila Nova de Gaia, Portugal, 4400-346
    • Hospital Luz Arrabida, S.A.
  • Matosinhos
    • Senhora Da Hora, Matosinhos, Matosinhos, Portugal, 4464-513
      • ULS De Matosinhos E.P.E.- Hospital Pedro Hispano
• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital_Cambridge
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry - WISDEM Centre
  • Liverpool, United Kingdom, L9 7AL
    • Aintree University Hospital
  • London, United Kingdom, E1 2AJ
    • Royal London Hospital - Blizard Institute
  • Swansea, United Kingdom, SA2 8PP
    • Joint Clinical Research Facility - Swansea
  • Taunton, United Kingdom, TA1 5DA
    • Musgrove Park Hospital
• United States
  • California
    • Covina, California, United States, 91723
      • Valley Clinical Trials
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Medical Research Institute_Honolulu
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research LLC
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Holston Medical Group_Bristol
  • Texas
    • Dallas, Texas, United States, 75231
      • North Texas Endocrine Center
  • Virginia
    • Arlington, Virginia, United States, 22206
      • Washington Cntr Weight Mgmt

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Male or female.
• Age above or equal to 18 years at the time of signing informed consent.
• Body mass index (BMI) greater than or equal to (>=) 35.0 kilograms per meter square (kg/m^2).

Exclusion criteria:

• Glycated haemoglobin (HbA1c) >= 6.5 percent (48 millimoles per mole [mmol/mol]) as measured by the central laboratory at screening.
• History of type 1 or type 2 diabetes.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CagriSema; Participants will receive once-weekly subcutaneous (s.c) injections of CagriSema (cagrilintide and semaglutide) after a dose escalation period of 16 weeks during the maintenance period for 88 weeks in the main phase. Participants randomised to this arm will be included in the extension phase for one year.	Drug: Semaglutide; Participants will receive semaglutide subcutaneously.; Drug: Cagrilintide; Participants will receive cagrilintide subcutaneously.
Placebo Comparator: Placebo; Participants will receive placebo matched to cagrilintide and semaglutide subcutaneously once weekly for 104 weeks. Participants randomised to this arm will be included in the extension phase for one year.	Drug: Placebo cagrilintide; Participants will receive placebo matched to cagrilintide subcutaneously.; Drug: Placebo semaglutide; Participants will receive placebo matched to semaglutide subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change in body weight	Measured in percentage (%).	From baseline (week 0) to week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who achieve greater than or equal to (>=) 20 percent body weight reduction	Measured as count of participants.	From baseline (week 0) to week 104
Number of participants who achieve >= 25 percent body weight reduction	Measured as count of participants.	From baseline (week 0) to week 104
Number of participants who achieve >= 30 percent body weight reduction	Measured as count of participants.	From baseline (week 0) to week 104
Change in waist circumference	Measured in centimeter (cm).	From baseline (week 0) to week 104
Change in waist to height ratio	Measured as ratio.	From baseline (week 0) to week 104
Change in Systolic Blood Pressure (SBP)	Measured in millimeter of mercury (mmHg).	From baseline (week 0) to week 104
Ratio to Baseline in Lipids: Total Cholesterol	Measured as ratio.	From baseline (week 0) to week 104
Ratio to Baseline in Lipids: High Density Lipoprotein (HDL) Cholesterol	Measured as ratio.	From baseline (week 0) to week 104
Ratio to Baseline in Lipids: Low Density Lipoprotein (LDL) Cholesterol	Measured as ratio.	From baseline (week 0) to week 104
Ratio to Baseline in Lipids: Very Low Density Lipoprotein (VLDL) Cholesterol	Measured as ratio.	From baseline (week 0) to week 104
Ratio to Baseline in Lipids: Triglycerides	Measured as ratio.	From baseline (week 0) to week 104
Ratio to Baseline in Lipids: Free fatty acids	Measured as ratio.	From baseline (week 0) to week 104
Ratio to Baseline in Lipids: Non-HDL cholesterol	Measured as ratio.	From baseline (week 0) to week 104
Change in Body Mass Index (BMI)	Measured in kilograms per meter square (kg/m^2).	From baseline (week 0) to week 104
Number of participants who achieve BMI less than 30 kg/m^2	Measured as count of participants.	At week 104
Change in Glycated Haemoglobin (HbA1c) (percentage points)	Measured in percentage points.	From baseline (week 0) to week 104
Change in HbA1c (millimoles per mole [mmol/mol])	Measured in mmol/mol.	From baseline (week 0) to week 104
Change in Fasting Plasma Glucose (FPG) (millimoles per liter [mmol/L])	Measured as mmol/L.	From baseline (week 0) to week 104
Change in FPG (milligrams per deciliter [mg/dL])	Measured as mg/dL.	From baseline (week 0) to week 104
Number of participants who achieve HbA1c less than (<) 5.7 percent and FPG < 100 mg/dL with prediabetes at baseline	Measured as count of participants.	From baseline (week 0) to week 104
Time to HbA1c < 5.7 percent and FPG < 100 mg/dL with prediabetes at baseline	Measured in days.	From baseline (week 0) to week 104
Number of participants who develop HbA1c >= 5.7 percent or FPG greater than (>) 100 mg/dL with normoglycemia at baseline	Measured as count of participants.	From baseline (week 0) to week 104
Number of participants who develop type 2 diabetes (T2D) as per American Diabetes Association (ADA) guideline	Measured as count of participants.	From baseline (week 0) to week 104
Time to T2D diagnosis as per ADA guideline	Measured in days.	From baseline (week 0) to week 104
Change in American College of Cardiology/American Heart Association (ACC/AHA) 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk score	Measured in percentage of risk. American College of Cardiology/American Heart Association (ACC/AHA) risk estimator calculates 10 year risk of atherosclerotic cardiovascular disease (ASCVD) using a formula which includes age, sex, race, total cholesterol, HDL cholesterol, systolic blood pressure, blood pressure medication use, diabetes status, smoking status; minimum score 0, maximum score 100 where higher score indicates higher risk of 10-year risk of atherosclerotic cardiovascular disease (ASCVD).	From baseline (week 0) to week 104
Number of participants who improve in >= 1 pre-existing cardiometabolic obesity related com-plication (ORC) (hypertension, prediabetes, or dyslipidaemia)	Measured as count of participants.	From baseline (week 0) to week 104
Ratio to baseline in C-reactive protein (CRP)	Measured as ratio.	From baseline (week 0) to week 104
Change in total fat mass by dual energy X-ray absorption (DXA) absolute to total body mass (kilogram [kg])	Measured in kg.	From baseline (week 0) to week 104
Change in total fat mass by DXA relative to total body mass (kg)	Measured in kg.	From baseline (week 0) to week 104
Change in total fat mass by DXA absolute to total body mass (percentage points)	Measured in percentage points.	From baseline (week 0) to week 104
Change in total fat mass by DXA relative to total body mass (percentage points)	Measured in percentage points.	From baseline (week 0) to week 104
Change in visceral fat mass by DXA, relative to baseline in visceral fat mass region (percentage)	Measured in percentage.	From baseline (week 0) to week 104
Change in visceral fat mass by DXA, relative to total amount of fat mass in visceral fat mass region (percentage)	Measured in percentage.	From baseline (week 0) to week 104
Change in visceral fat mass by DXA, relative to baseline in visceral fat mass region (percentage points)	Measured in percentage points.	From baseline (week 0) to week 104
Change in visceral fat mass by DXA, relative to total amount of fat mass in visceral fat mass region (percentage points)	Measured in percentage points.	From baseline (week 0) to week 104
Change in lean body mass by DXA absolute to total body mass (kg)	Measured in kg.	From baseline (week 0) to week 104
Change in lean body mass by DXA relative to total body mass (kg)	Measured in kg.	From baseline (week 0) to week 104
Change in lean body mass by DXA absolute to total body mass (percentage points)	Measured in percentage points.	From baseline (week 0) to week 104
Change in lean body mass by DXA relative to total body mass (percentage points)	Measured in percentage points.	From baseline (week 0) to week 104
Change in Short Form (SF)-36 Physical functioning score	Measured as score points. The 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. The scores are norm-based scores, i.e. transformed to a scale where the 2009 United States general population has a mean of 50 and a standard deviation of 10. Physical Functioning score ranges from 19.0-57.6, with higher scores indicating better functional health and well-being.	From baseline (week 0) to week 104
Change in Impact of Weight on Quality of Life-Lite for clinical trials (IWQOL-Lite-CT): Physical Function Score	Measured as score points. IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Physical function score ranges from 0 to 100, with higher scores indicating better levels of functioning.	From baseline (week 0) to week 104
Change in IWQOL-Lite-CT: Physical Score	Measured as score points. IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Physical score ranges from 0 to 100, with higher scores indicating better levels of functioning.	From baseline (week 0) to week 104
Change in IWQOL-Lite-CT: Psychosocial score	Measured as score points. IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Psychosocial score ranges from 0 to 100, with higher scores indicating better levels of functioning.	From baseline (week 0) to week 104
Change in IWQOL-Lite-CT: Total score	Measured as score points. IWQOL-Lite-CT measures weight-related physical and psychosocial functioning. The measure consists of 20 items yielding 3 composite scores, and 1 total score. Total score ranges from 0 to 100, with higher scores indicating better levels of functioning.	From baseline (week 0) to week 104
Change in Impact of Weight on Daily Activities Questionnaire (IWDAQ) Composite score	Measured as score points. IWDAQ is an 18-item measure that uses an adaptive design to provide a personalised assessment of daily activity limitations associated with excess weight. At the baseline assessment the study participants choose the 3 activities (items) they would most like to improve the weight loss and rate the degree of limitation in each of these activities. At follow-up assessments, the study participants again rate the degree of current limitation in each of the same 3 activities. The measure yields the IWDAQ composite score with a score range from 3 to 15 with higher scores indicating greater personalised activity limitation.	From baseline (week 0) to week 104
Change in Control of Eating questionnaire (CoEQ): Craving Control score	Measured as score points. CoEQ is a 19-item multidimensional patient reported outcome (PRO) that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving control subscale, the subscale score is reversed so that a higher score represents a greater level of craving control.	From baseline (week 0) to week 104
Change in CoEQ: Positive Mood score	Measured as score points. CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), and craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the Positive Mood subscale, item 6 'How anxious have you felt?' is reversed.	From baseline (week 0) to week 104
Change in CoEQ: Craving for Sweets score	Measured as score points. CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving sweets food subscale, higher score represents a greater level of craving.	From baseline (week 0) to week 104
Change in CoEQ: Craving for Savoury score	Measured as score points. CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the craving savoury food subscale, higher score represents a greater level of craving.	From baseline (week 0) to week 104
Change in CoEQ: Hunger score	Measured as score points. CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the hunger subscale, higher score represents a greater level of craving.	From baseline (week 0) to week 104
Change in CoEQ: Satiety score	Measured as score points. CoEQ is a 19-item multidimensional PRO that assesses the experience of hunger, satiety, and severity and type of food cravings. CoEQ consists of 4 subscales that measure craving control (5 items), positive mood (4 items), craving for sweet (4 items), craving for savoury food (4 items), and 2 single items that address hunger and satiety. Each item is evaluated on a 0-10 (i.e., 11-point) numeric rating scale. The total score for each subscale is calculated as the sum of the item scores divided by the number of items in the subscale. Scores ranges are thus: Craving Control 0-50/5 = 0-10); Positive Mood (0-40/4 = 0-10); Craving Sweet (0-40/4 = 0-10); Craving Savoury food (0-40/4 = 0-10); single items that address hunger and satiety (0-10). For the satiety subscale, higher score represents a greater level of craving.	From baseline (week 0) to week 104
CagriSema s.c. 2.4 mg/2.4 mg versus placebo: Number of Treatment Emergent Adverse Events (TEAEs)	Measured as count of events.	From baseline (week 0) to week 104
CagriSema s.c. 2.4 mg/2.4 mg versus placebo: Number of Treatment Emergent Serious Adverse Events (TESAEs)	Measured as count of events.	From baseline (week 0) to week 104
CagriSema s.c. 2.4 mg/2.4 mg versus CagriSema s.c. dose tapering algorithm: Number of TEAEs	Measured as count of events.	From week 104 to end of study (week 162)
CagriSema s.c. 2.4 mg/2.4 mg versus CagriSema s.c. dose tapering algorithm: Number of TESAEs	Measured as count of events.	From week 104 to end of study (week 162)
CagriSema 2.4 mg/2.4 mg: Number of TEAEs	Measured as count of events.	From week 104 to end of study (week 162)
CagriSema 2.4 mg/2.4 mg: Number of TESAEs	Measured as count of events.	From week 104 to end of study (week 162)
Number of participants who achieve HbA1c >= 6.5 percent or FPG >= 126 mg/dL with prediabetes at baseline	Measured as count of participants.	From baseline (week 0) to week 104
Time to HbA1c >= 6.5 percent or FPG >= 126 mg/dL with prediabetes at baseline	Measured in days.	From baseline (week 0) to week 104

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): February 10, 2025
• Primary Completion (Estimated): August 28, 2028
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): January 17, 2025

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide; cagrilintide
• Other Study ID Numbers: NN9838-7859; U1111-1304-7430 (Other Identifier: World Health Organization (WHO)); 2024-512144-39 (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