A Research Study to See How Well New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Levels in People With Type 2 Diabetes (T2D), Compared to Daily Insulin Glargine (COMBINE 4)

Phase 3

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: IcoSema; Drug: Insulin glargine

• Registration Number: NCT06269107
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin glargine (mentioned as insulin glargine in this form) taken daily in people with type 2 diabetes. The study will look at how well IcoSema controls blood sugar levels as compared to insulin glargine in people with type 2 diabetes who do not have their blood sugar properly controlled with other oral diabetes medicines. Participant will either get IcoSema or insulin glargine. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine in many countries. The study will last for about 11 months (47 weeks).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-02-13
• Study First Submitted QC: 2024-02-13
• Study Start: 2024-02-15
• Study First Posted: 2024-02-21
• Primary Completion: 2025-05-27
• Study Completion: 2025-07-08
• Status Verified: 2025-08
• Last Update Submitted: 2025-08-29
• Last Update Posted: 2025-09-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 485

Inclusion Criteria

• Male or female and age above or equal to 18 years at the time of signing the informed consent.

• Diagnosed with T2D greater than or equal to (≥) 180 days before screening.

• HbA1c ≥ 8.0% (≥ 64.0 millimoles per mole [mmol/mol]) as assessed by central laboratory on the day of screening.

• Insulin naïve. Short term insulin treatment for a maximum of 14 consecutive days before screening is allowed, as is prior insulin treatment for gestational diabetes.

• Currently treated with 1-3 oral anti diabetic drug (OADs) with stable daily doses ≥ 90 days before screening comprising any of the following anti diabetic drug(s) at effective or maximum tolerated dose.

  • Metformin
  • Sulfonylureas
  • Meglitinides (glinides)
  • Dipeptidyl peptidase (DPP) 4 inhibitors
  • Sodium glucose co transporter 2 inhibitors
  • Alpha glucosidase inhibitors
  • Thiazolidinediones
  • Marketed oral combination products only including the products listed above.

• Body mass index (BMI) less than or equal to (≤) 40.0 kilogram per square meter (kg/m^2).

Exclusion Criteria

• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbaring potential and not using highly effective contraceptive method.
• 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).
• Any episodes of diabetic ketoacidosis or treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
• Presence or history of pancreatitis (acute or chronic) within 180 days before screening.
• Any of the following: Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening.
• Chronic heart failure classified as being in New York Heart Association Class IV at screening.
• Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IcoSema	IcoSema	Participants will receive once weekly IcoSema subcutaneously with or without oral anti diabetic drugs for 40 weeks.
Insulin glargine	Insulin glargine	Participants will receive once daily insulin glargine subcutaneously with or without oral anti diabetic drugs for 40 weeks.

Primary Outcome Measures

Name	Time	Method
Change in glycated haemoglobin (HbA1c)	From baseline (week 0) to week 40	Measured in percentage (%)-point.

Secondary Outcome Measures

Name	Time	Method
Time spent greater than (>) 10.0 mmol/L (180 mg/dL)	From week 36 to week 40	Measured in % of readings.
Change in body weight	From baseline (week 0) to week 40	Measured in kilogram (kg).
Time in range 3.9-10.0 millimoles per liter (mmol/L) (70-180 milligram per deciliter [mg/dL])	From week 36 to week 40	Measured in % of readings.
Time spent less than (<) 3.0 mmol/L (54 mg/dL)	From week 36 to week 40	Measured in % of readings.
Weekly basal insulin dose	From week 38 to week 40	Measured in units of insulin.
Change in fasting plasma glucose (FPG)	From baseline (week 0) to week 40	Measured in mmol/l.
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)	From baseline (week 0) to week 45	Measured in number of episodes.
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction	From baseline (week 0) to week 40	The DTSQs items are scored on a 7-point graded response scale ranging from 0 to 6. Score ranges from 0 to 36. Higher scores indicate greater the satisfaction with medication.
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by blood glucose meter) or severe hypoglycaemic episodes (level 3)	From baseline (week 0) to week 45	Measured in number of episodes.
Number of severe hypoglycaemic episodes (level 3)	From baseline (week 0) to week 45	Measured in number of episodes.

Trial Locations

Locations (90)

Scripps Whittier Diabetes Inst; 🇺🇸 La Jolla, California, United States

First Valley Med Grp Lancaster; 🇺🇸 Lancaster, California, United States

Desert Oasis Hlthcr Med Group; 🇺🇸 Palm Springs, California, United States

Clinical Trials Research_Sacramento; 🇺🇸 Sacramento, California, United States

Northeast Research Institute; 🇺🇸 Fleming Island, Florida, United States

Clinical Research of Cent FL; 🇺🇸 Winter Haven, Florida, United States

Atlanta Diabetes Associates; 🇺🇸 Atlanta, Georgia, United States

Elite Clinical Trials; 🇺🇸 Blackfoot, Idaho, United States

Cedar-Crosse Research Center; 🇺🇸 Chicago, Illinois, United States

Endeavor Health; 🇺🇸 Skokie, Illinois, United States

Scroll for more (80 remaining)