REIMAGINE 2

CompletedPhase 3

A Research Study to See How Well CagriSema Compared to Semaglutide, Cagrilintide and Placebo Lowers Blood Sugar and Body Weight in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor

Efficacy and Safety of Co-administered Cagrilintide and Semaglutide (CagriSema) s.c. in Doses 2.4/2.4 mg and 1.0/1.0 mg Once Weekly Versus Semaglutide 2.4 mg and 1.0 mg, Cagrilintide 2.4 mg and Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Metformin With or Without an SGLT2 Inhibitor

Lead sponsor

Novo Nordisk A/S

Assets

CagriSema / cagrilintide / Semaglutide

Listed sites

405

Recruiting sites

—

Enrollment

2,734

actual

Study population

Obesity / overweight, Type 2 diabetes

Key I/E criteria

•BMI ≥25•HbA1c 7-10.5%

Primary endpoint

•HbA1c, change

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 IDNCT06065540

Org study IDNN9388-4896

Secondary ID2022-502678-18

Secondary IDU1111-1283-0427World Health Organization (WHO)

Timeline

Milestones

Study start2023-09-27actual

Study first posted2023-10-04actual

Primary completion2025-11-19actual

Study completion2026-01-06actual

Last update posted2026-01-22actual

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 (sex at birth).

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

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

•Stable daily dose(s) greater than or equal to 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 Sodium-Glucose Cotransporter-2 (SGLT2) inhibitors.

•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 metre ( 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

•Renal impairment with estimated Glomerular Filtration Rate (eGFR) less than 30 milliliters per minute per 1.73 square metre (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.

Endpoints (38)

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

Cardiometabolic biomarkers

Weight & body composition

Patient-reported / QoL

Safety / tolerability / PK

Weight & body composition

8 endpoints

Secondary/protocol endpoint

CagriSema versus cagrilintide: 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

Secondary/protocol endpoint

CagriSema versus semaglutide: 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

Secondary/protocol endpoint

Cagrilintide versus placebo: 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

Secondary/protocol endpoint

CagriSema versus semaglutide: Achievement of greater than or equal to (>=) 10 percent (%) weight reduction

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

≥10% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: Achievement of >= 15 % weight reduction

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

≥15% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: 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

CagriSema versus semaglutide: Achievement of ≥ 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

CagriSema versus semaglutide: Change in waist circumference

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

Waist circumference, change

change from baseline, improvement

Glycemic / diabetes

13 endpoints

Primary/protocol endpoint

CagriSema (dose 1) versus semaglutide (dose 1): 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

CagriSema versus cagrilintide: Change in 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

CagriSema (dose 1) versus semaglutide (dose 2): Change in 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

Cagrilintide versus placebo: Change in 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

CagriSema (pooled doses) versus semaglutide (pooled doses): Continuous Glucose Monitoring (CGM) - Change in Time in Range (TIR) 3.9-10.0 millimoles per litre (mmol/L) (70-180 milligrams per decilitre [mg/dL])

Time frame:From baseline (week -3) to end of treatment (week 68)

CGM time-in-range

change from baseline, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: CGM - Change in time in Tight Target Range (TITR) 3.9-7.8 (mmol/L) (70-140 mg/dL)

Time frame:From baseline (week -3) to end of treatment (week 68)

change from baseline, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: CGM - Change in Time In Range (TIR) 3.9-10.0 mmol/L (70-180 mg/dL)

Time frame:From baseline (week -3) to end of treatment (week 68)

CGM time-in-range

change from baseline, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: Change in Fasting Plasma Glucose (FPG)

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

CagriSema versus semaglutide: Achievement of HbA1c target values of less than (<) 7.0% (<53 millimoles per mole [mmol/mol])

Time frame:At end of treatment (week 68)

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

CagriSema versus semaglutide: Achievement of HbA1c target values of less than or equal to (≤)6.5% (≤48 mmol/mol)

Time frame:At end of treatment (week 68)

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

CagriSema versus semaglutide: CGM - Change in time above range, >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

CagriSema versus semaglutide: CGM - Change in time above range, >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/low confidence

CagriSema versus semaglutide: CGM - Within-day glycaemic variability (% coefficient of variation [CV])

Time frame:At end of treatment (week 68)

descriptive, improvement

Cardiometabolic biomarkers

10 endpoints

Secondary/protocol endpoint

CagriSema versus semaglutide: 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

CagriSema versus semaglutide: Ratio to baseline in triglycerides

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

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

CagriSema versus semaglutide: Ratio to baseline in non-High Density Lipoprotein (HDL) cholesterols

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

Non-HDL cholesterol, change

ratio, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: Ratio to baseline in high sensitivity C-Reactive Protein (hsCRP)

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

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

CagriSema versus semaglutide: 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

CagriSema versus semaglutide: Ratio to baseline in total cholesterol

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

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

CagriSema versus semaglutide: Ratio to baseline in HDL cholesterol

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

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

CagriSema versus semaglutide: Ratio to baseline in low-density lipoprotein (LDL) cholesterol

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

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

CagriSema versus semaglutide: Ratio to baseline in very low-density lipoprotein (VLDL) cholesterol

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

VLDL, change

ratio, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: Ratio to baseline in free fatty acids

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

Free fatty acids, change

ratio, improvement

Patient-reported / QoL

4 endpoints

Secondary/protocol endpoint

CagriSema versus semaglutide: Change in Short Form (SF)-36v score- Physical component summary score

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

SF-36 physical

change from baseline, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: Change in SF-36v2 score- Mental component summary score

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

SF-36 mental

change from baseline, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ) score

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

change from baseline, improvement

Secondary/protocol endpoint

CagriSema versus semaglutide: Change in Treatment Related Impact Measure for Diabetes (TRIM-D) score

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

change from baseline, improvement

Safety / tolerability / PK

3 endpoints

Secondary/protocol endpoint

CagriSema versus semaglutide, placebo and cagrilintide: 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

CagriSema versus semaglutide: 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

CagriSema versus semaglutide: Number of severe hypoglycaemic episodes (level 3)

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

Buse JB, Bajaj HS, Dalskov SM, Donaldson L, Hansen Duus HH, Fabricius TW, Haluzik M, Lingvay I, Pedersen SD, Pratley RE, Jain AB; REIMAGINE 2 study group. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study. Lancet Diabetes Endocrinol. 2026 Jun 7:S2213-8587(26)00125-7. doi: 10.1016/S2213-8587(26)00125-7. Online ahead of print.
PMID42251859via clinicaltrials gov reference derived

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.