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COMBINE 1
CompletedPhase 3Results postedA Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Weekly Insulin Icodec
A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Once Weekly Insulin Icodec, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With Daily Basal Insulin.
Lead sponsor
Asset
Semaglutide
GLP-1 agonist
Listed sites
281
Recruiting sites
—
Enrollment
1,291
actual
Study population
Type 2 diabetes
Key I/E criterion
—
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
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
Eligibility criteria
Key inclusion criteria
1. Male or female and age above or equal to 18 years at the time of signing informed consent.
2. Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
3. HbA1c of 7.0 10.0% (53.0 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
4. Treated with once daily or twice daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20- 80 units/day for 90 days or more before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti diabetic drugs with stable doses for 90 days or more before screening:
5. Body mass index (BMI) below or equal to 40.0 kg/m^2. (a) Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation.
Key exclusion criteria
1. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a highly effective 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 (as declared by the participant or in the medical records.) 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 (20)
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
Weight & body composition
2 endpointsChange in Body Weight
Time frame:Baseline (Week 0), Week 52
Body weight, absolute change (kg)
change from baseline, improvement
Posted result
| Group | Value (mean), Kilogram (Kg) | 95% CI |
|---|---|---|
| IcoSema | -3.71 | — |
| Insulin Icodec | 1.96 | — |
Change in Body Weight
Time frame:Baseline (Week 0), Week 52
Body weight, absolute change (kg)
change from baseline, improvement
Glycemic / diabetes
12 endpointsChange in Glycated Haemoglobin (HbA1c)
Time frame:Baseline (Week 0), Week 52
HbA1c, change
change from baseline, improvement
LOINC 4548-4
Posted result
| Group | Value (mean), Percentage point of HbA1c | 95% CI |
|---|---|---|
| IcoSema | -1.60 | — |
| Insulin Icodec | -0.90 | — |
Change in Glycated Haemoglobin (HbA1c)
Time frame:Baseline (Week 0), Week 52
HbA1c, change
change from baseline, improvement
LOINC 4548-4
Percentage of Time in Range 3.9-10.0 mmol/L (70-180 mg/dL) Using Continuous Glucose Monitoring (CGM) System, Dexcom G6
Time frame:From week 48 to week 52
CGM time-in-range
descriptive, improvement
Posted result
| Group | Value (mean), Percentage of time | 95% CI |
|---|---|---|
| IcoSema | 75.9 | — |
| Insulin Icodec | 61.9 | — |
Percentage of Time Spent < 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System, Dexcom G6
Time frame:From week 48 to week 52
CGM time-below-range
descriptive, improvement
Posted result
| Group | Value (mean), Percentage of time | 95% CI |
|---|---|---|
| IcoSema | 0.27 | — |
| Insulin Icodec | 0.33 | — |
Percentage of Time Spent > 10.0 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System, Dexcom G6
Time frame:From week 48 to week 52
CGM time-above-range
descriptive, improvement
Posted result
| Group | Value (mean), Percentage of time | 95% CI |
|---|---|---|
| IcoSema | 23.2 | — |
| Insulin Icodec | 36.7 | — |
Change in Fasting Plasma Glucose (FPG)
Time frame:Baseline (Week 0), Week 52
Fasting glucose, change
change from baseline, improvement
LOINC 1558-6
Posted result
| Group | Value (mean), Millimoles per litre (mmol/L) | 95% CI |
|---|---|---|
| IcoSema | -1.90 | — |
| Insulin Icodec | -1.65 | — |
Weekly Basal Insulin Dose
Time frame:From week 50 to week 52
descriptive
Posted result
| Group | Value (mean), Units of insulin | 95% CI |
|---|---|---|
| IcoSema | 170.6 | — |
| Insulin Icodec | 366.5 | — |
Percentage of Time in Range 3.9-10.0 mmol/L (70-180 mg/dL) Using Continuous Glucose Monitoring (CGM) System, Dexcom G6
Time frame:From week 48 to week 52
CGM time-in-range
descriptive, improvement
Percentage of Time Spent < 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System, Dexcom G6
Time frame:From week 48 to week 52
CGM time-below-range
percent change from baseline, improvement
Percentage of Time Spent > 10.0 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System, Dexcom G6
Time frame:From week 48 to week 52
CGM time-above-range
descriptive, improvement
Change in Fasting Plasma Glucose (FPG)
Time frame:Baseline (Week 0), Week 52
Fasting glucose, change
change from baseline, improvement
LOINC 1558-6
Weekly Basal Insulin Dose
Time frame:From week 50 to week 52
descriptive
Safety / tolerability / PK
6 endpointsNumber of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 Millimoles Per Litre [mmol/L] (54 Milligram Per Decilitre [mg/dL]), Confirmed by Blood Glucose [BG] Meter) or Severe Hypoglycaemic Episodes (Level 3)
Time frame:From baseline week 0 to week 57
Documented hypoglycemia
event count, event
componentsDocumented hypoglycemia, Severe hypoglycemia
Posted result
| Group | Value (number), Episodes | 95% CI |
|---|---|---|
| IcoSema | 91 | — |
| Insulin Icodec | 424 | — |
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 week 57
Documented hypoglycemia
event count, event
Posted result
| Group | Value (number), Episodes | 95% CI |
|---|---|---|
| IcoSema | 90 | — |
| Insulin Icodec | 419 | — |
Number of Severe Hypoglycaemic Episodes (Level 3)
Time frame:From baseline week 0 to week 57
Severe hypoglycemia
event count, event
Posted result
| Group | Value (number), Episodes | 95% CI |
|---|---|---|
| IcoSema | 1 | — |
| Insulin Icodec | 5 | — |
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 Millimoles Per Litre [mmol/L] (54 Milligram Per Decilitre [mg/dL]), Confirmed by Blood Glucose [BG] Meter) or Severe Hypoglycaemic Episodes (Level 3)
Time frame:From baseline week 0 to week 57
Documented hypoglycemia
event count, event
componentsDocumented hypoglycemia, Severe hypoglycemia
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 week 57
Documented hypoglycemia
event count, event
Number of Severe Hypoglycaemic Episodes (Level 3)
Time frame:From baseline week 0 to week 57
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
- The lancet. Diabetes & endocrinology2025 Jul (month)PMID40482671doi:10.1016/S2213-8587(25)00096-8via clinicaltrials gov reference derived + pubmed nct search
Provenance
Sources
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.