A research study to see how weekly IcoSema controls blood sugar levels when compared with daily insulin degludec/insulin aspart (IDegAsp) in people with poorly controlled type 2 diabetes (COMBINE 5)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

completed 9 Dec 2025

Decision date (initial)

2025-12-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2025-521150-42-00

WHO UTN

U1111-1318-7917

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To confirm non-inferiority of once weekly IcoSema versus once or twice daily insulin degludec/insulin aspart, both treatment arms with or without OADs, with respect to glycaemic control measured by change in HbA1c from baseline after 40 weeks in participants with T2D inadequately controlled with pre-mixed insulin treatment using a non-inferiority margin of 0.3%-point.

Secondary objectives 2

1. To confirm superiority of once weekly IcoSema versus once or twice daily insulin degludec/insulin aspart, both treatment arms with or without OADs, in participants with T2D inadequately controlled with pre-mixed insulin treatment with respect to: Change in body weight from baseline after 40 weeks Number of clinically significant hypoglycaemic (level 2) or severe hypoglycaemic (level 3) episodes during 40 weeks and the 5 week follow up period Weekly insulin dose (total) from week 38 to week 40 Change in Diabetes Treatment Satisfaction Questionnaire – status version (DTSQs) total treatment satisfaction from baseline after 40 weeks Change in HbA1c from baseline after 40 weeks.
2. To compare parameters of glycaemic control, patient reported outcomes and safety of once weekly IcoSema versus once or twice daily insulin degludec/insulin aspart, both treatment arms with or without OADs, in participants with T2D inadequately controlled with pre-mixed insulin treatment.

Conditions and MedDRA coding

Type 2 diabetes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female
2. Age 18 years or above at the time of signing the informed consent.
3. Diagnosed with T2D ≥ 180 days before screening.
4. HbA1c of 7.0-10.0% (53.0-85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
5. Treated with once-daily or twice-daily pre-mixed insulin (containing 25%, 30% or 50% fast/rapid acting component) 20-80 units/day ≥ 90 days before screening. The treatment can be with or without any of the following anti-diabetic drugs with stable daily doses ≥ 90 days before screening: Metformin Sulfonylureas Meglitinides (glinides) DPP-4 inhibitors Sodium-glucose co-transporter 2 inhibitors Alpha-glucosidase-inhibitors Thiazolidinediones Marketed oral combination products only including the products listed above.
6. Body mass index (BMI) ≤ 40.0 kg/m2.

Exclusion criteria 9

1. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive method.
2. Anticipated initiation or change in concomitant medication (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or systemic corticosteroids).
3. Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
4. Any episodes of diabetic ketoacidosis within 90 days before screening.
5. Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
6. Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
7. Chronic heart failure classified as being in New York Heart Association Class IV at screening.
8. Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.
9. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 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

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in HbA1c

Secondary endpoints 15

1. Change in body weight
2. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)
3. Weekly insulin dose (total)
4. Change in DTSQs total treatment satisfaction
5. Change in HbA1c
6. Change in mean 7-point SMPG profiles
7. Change in mean post-prandial glucose increment (over all meals)
8. Time spent < 3.0 mmol/L (54 mg/dL)
9. Time spent > 10.0 mmol/L (180 mg/dL)
10. Change in time in range 3.9-10.0 mmol/L (70-180 mg/dL)
11. Change in FPG
12. Change in Treatment Related Impact Measure - Diabetes (TRIM-D) score
13. Change in EQ-5D-5L score
14. Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L [54 mg/dL], confirmed by BG meter)
15. Number of severe hypoglycaemic episodes (level 3)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 10

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications