REDEFINE 2

CompletedPhase 3

A Research Study to See How Well CagriSema Helps People With Type 2 Diabetes and Excess Body Weight Lose Weight

Efficacy and Safety of Cagrilintide s.c. 2.4 mg in Combination With Semaglutide s.c. 2.4 mg (CagriSema s.c. 2.4 mg/2.4 mg) Once-weekly in Participants With Overweight or Obesity and Type 2 Diabetes

Lead sponsor

Novo Nordisk A/S

Assets

CagriSema / cagrilintide / Semaglutide

Listed sites

179

Recruiting sites

—

Enrollment

1,200

actual

Study population

Obesity / overweight, Type 2 diabetes

Key I/E criterion

•HbA1c 7-10%

Primary endpoints

•Body weight, % change•≥5% weight-loss responders

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT05394519

Org study IDNN9838-4609

Secondary ID2021-005121-24

Secondary IDjRCT2031220671jRCT (Japan)

Secondary IDU1111-1267-4287World Health Organization (WHO)

Timeline

Milestones

Study first posted2022-05-27actual

Study start2023-02-01actual

Primary completion2025-01-28actual

Study completion2025-02-03actual

Last update posted2026-01-28actual

Assets

Investigational agents

CagriSema / cagrilintide Semaglutide

Study populations

Who this study enrolls

Obesity / overweightType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Male or female

•Age above or equal to 18 years at the time of signing informed consent

•BMI greather than or equal to 27.0 kg/m^2

•Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days before screening

•Treatment with either lifestyle intervention, or treatment with 1-3 marketed oral antidiabetic drugs (OAD)s (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2 inhibitor (SGLT2i), thiazolidinediones, or sulphonylureas (SU)s as a single agent or in combination) according to local label

•Treatment with oral antidiabetic drugs should be stable (same drug(s), dose and dosing frequency) for at least 90 days before screening

•HbA1c 7%-10% (53-86 mmol/mol) (both inclusive) as measured by the central laboratory at screening

Exclusion criteria

•Clinically significant or severe hypoglycaemia within 6 months before screening or history of hypoglycaemia unawareness

•Renal impairment with estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m^2, as measured by the central laboratory at screening

•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.

Endpoints (36)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes

Weight & body composition

Patient-reported / QoL

Cardiometabolic biomarkers

Safety / tolerability / PK

Weight & body composition

8 endpoints

Primary/protocol endpoint

Relative change in body weight

Time frame:From baseline (week 0) to end of treatment (week 68)

Body weight, % change

percent change from baseline, improvement

Primary/protocol endpoint

Achievement of greater than or equal to (≥) 5% weight reduction

Time frame:From baseline (week 0) to end of treatment (week 68)

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Achievement of ≥ 20% weight reduction

Time frame:From baseline (week 0) to end of treatment (week 68)

≥20% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Relative change in body weight

Time frame:From baseline (week 0) to week 20

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in waist circumference

Time frame:From baseline (week 0) to end of treatment (week 68)

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Change in body weight

Time frame:From baseline (week 0) to end of treatment (week 68)

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in body mass index (BMI)

Time frame:From baseline (week 0) to end of treatment (week 68)

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Improvement in weight category (BMI, underweight below 18.5, normal weight 18.5 to below 25, overweight 25.0 to below 30, obesity class I 30 to below 35, obesity class II 35 to below 40, obesity class III above 40)

Time frame:From baseline (week 0) to end of treatment (week 68)

categorical status, improvement

Glycemic / diabetes

12 endpoints

Secondary/protocol endpoint

Change in Glycated Haemoglobin (HbA1c)

Time frame:From baseline (week 0) to end of treatment (week 68)

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Achievement of HbA1c less than or equal to (≤) 6.5%

Time frame:At end of treatment (week 68)

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in Fasting Plasma Glucose (mmol/L)

Time frame:From baseline (week 0) to end of treatment (week 68)

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in Fasting Plasma Glucose (mg/dL)

Time frame:From baseline (week 0) to end of treatment (week 68)

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Ratio to baseline in fasting serum insulin

Time frame:From baseline (week 0) to end of treatment (week 68)

ratio, improvement

Secondary/protocol endpoint

Continuous glucose monitoring: Change in mean glucose (mmol/L)

Time frame:From baseline (week 0) to end of treatment (week 68)

change from baseline, improvement

Secondary/protocol endpoint

Continuous glucose monitoring: Change in mean glucose (mg/L)

Time frame:From baseline (week 0) to end of treatment (week 68)

change from baseline, improvement

Secondary/protocol endpoint

CGM: Change in time above range (TAR) >10.0 mmol/L (>180 mg/dL)

Time frame:From baseline (week 0) to end of treatment (week 68)

CGM time-above-range

change from baseline, improvement

Secondary/protocol endpoint

CGM: Change in time in range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL)

Time frame:From baseline (week 0) to end of treatment (week 68)

CGM time-in-range

change from baseline, improvement

Secondary/protocol endpoint

CGM: Change in time above high range (TAHR) >13.9 mmol/L (>250 mg/dL)

Time frame:From baseline (week 0) to end of treatment (week 68)

CGM time-above-range

change from baseline, improvement

Secondary/protocol endpoint

CGM: Change in time in tight range (TITR) 3.9-7.8 mmol/L (71-140 mg/dL)

Time frame:From baseline (week 0) to end of treatment (week 68)

change from baseline, improvement

Secondary/protocol endpoint

CGM: Within-day glycaemic variability (% CV)

Time frame:At end of treatment (week 68)

descriptive

Cardiometabolic biomarkers

4 endpoints

Secondary/protocol endpoint

Change in Systolic Blood Pressure (SBP)

Time frame:From baseline (week 0) to end of treatment (week 68)

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change in Diastolic Blood Pressure (DBP)

Time frame:From baseline (week 0) to end of treatment (week 68)

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Secondary/protocol endpoint

Ratio to baseline in C-reactive protein (CRP)

Time frame:From baseline (week 0) to end of treatment (week 68)

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

Ratio to baseline in lipids: Total cholesterol, High-density lipoprotein (HDL) cholesterol, Low-density lipoprotein (LDL) cholesterol, Very low-density lipoprotein (VLDL) cholesterol, Triglycerides and Free fatty acids

Time frame:From baseline (week 0) to end of treatment (week 68)

ratio, improvement

Patient-reported / QoL

8 endpoints

Secondary/protocol endpoint

Change in Impact of Weight on Quality Of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Physical Function score

Time frame:From baseline (week 0) to end of treatment (week 68)

IWQOL-Lite physical

change from baseline, improvement

Secondary/protocol endpoint

Change in Short Form-36 Version 2.0 Health Survey Acute (SF-36v2 Acute) Physical Functioning score

Time frame:From baseline (week 0) to end of treatment (week 68)

SF-36 physical

change from baseline, improvement

Secondary/protocol endpoint

Change in IWQOL-Lite-CT: Total score, Physical and Psycosocial score

Time frame:From baseline (week 0) to end of treatment (week 68)

IWQOL-Lite total

change from baseline, improvement

Secondary/protocol endpoint

Change in Control of Eating Questionnaire (CoEQ): Craving Control score, Positive Mood score, Craving for Sweet score, Craving for Savoury food score, Hunger score and Satiety score

Time frame:From baseline (week 0) to end of treatment (week 68)

PGI, change

change from baseline, improvement

Secondary/protocol endpoint

Achievement of at least 14.6-point increase (yes/no) in IWQOL-Lite-CT Physical Function score

Time frame:From baseline (week 0) to end of treatment (week 68)

IWQOL-Lite physical

threshold achievement, improvement

Secondary/protocol endpoint

Achievement of at least 3.7-point increase (yes/no) in SF-36v2 Acute Physical Functioning score

Time frame:From baseline (week 0) to end of treatment (week 68)

SF-36 physical

threshold achievement, improvement

Secondary/protocol endpoint

Change in IWQOL-Lite-CT Physical Function score

Time frame:From baseline (week 0) to end of treatment (week 68)

IWQOL-Lite physical

change from baseline, improvement

Secondary/protocol endpoint

Achievement of at least 14.6-point increase (yes/no) in IWQOL-Lite -CT Physical Function score for subgroup

Time frame:From baseline (week 0) to end of treatment (week 68)

IWQOL-Lite physical

threshold achievement, improvement

Safety / tolerability / PK

4 endpoints

Secondary/protocol endpoint

Number of Treatment Emergent Adverse Events (TEAEs)

Time frame:From baseline (week 0) to end of study (week 75)

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Number of Treatment Emergent Serious adverse events (TESAEs)

Time frame:From baseline (week 0) to end of study (week 75)

Serious AEs (any)

event count, event

Secondary/protocol endpoint

Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)

Time frame:From baseline (week 0) to end of study (week 75)

Documented hypoglycemia

event count, event

Secondary/protocol endpoint

Number of severe hypoglycaemic episodes (level 3): hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery, with no specific glucose threshold

Time frame:From baseline (week 0) to end of study (week 75)

Severe hypoglycemia

event count, event

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.
The New England journal of medicine2025 Aug 14PMID40544432doi:10.1056/NEJMoa2502082via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.