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Completed

NCT Number: NCT05352815

A 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

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin icodec taken once a week in people with type 2 diabetes.

The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to insulin icodec.

Participants will either get IcoSema or insulin icodec. Which treatment participants get is decided by chance. IcoSema and insulin icodec are both new medicines that doctors cannot prescribe.

Participants will get IcoSema or insulin icodec, which participants must inject once a week with a pen, which has a small needle, in a skin fold in the thigh, upper arm, or stomach.

The study will last for about 1 year and 1 month. Participants will have 21 clinic visits, 31 phone/video calls with the study doctor, and 4 contacts with the site that can either be clinic visits or phone/video calls At 11 clinic visits participants will have blood samples taken. At 7 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit.

Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.

Not applicable for China: Participants will be asked to wear a sensor that measures their blood sugar level all the time during a 5 week period at the end of the study.

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Key information

Conditions

Diabetes Mellitus, Type 2 Diabetes Mellitus Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

The Canberra Hospital_Garran, Garran, Australian Capital Territory, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key inclusion criteria

  • Male or female and age above or equal to 18 years at the time of signing informed consent.
  • Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
  • HbA1c of 7.0 10.0% (53.0 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
  • 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:
  • Metformin
  • Sulfonylureas (a)
  • Meglitinides (glinides) (a)
  • DPP 4 inhibitors (a)
  • Sodium glucose co transporter 2 inhibitors
  • Alpha glucosidase inhibitors
  • Thiazolidinediones
  • Marketed oral combination products only including the products listed above.
  • 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

  • Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a 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).
  • Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
  • Any episodes (as declared by the participant or in the medical records.) of diabetic ketoacidosis 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.

Treatment and study plan

IcoSema

Drug

Participants will receive once weekly IcoSema subcutanously (s.c. under the skin) with or without oral anti diabetic drugs for 52 weeks.

Insulin icodec

Drug

Participants will receive once weekly Insulin icodec subcutanously (s.c. under the skin) with or without oral anti diabetic drugs for 52 weeks.

Primary outcomes

  1. Change in Glycated Haemoglobin (HbA1c)

    Time frame: Baseline (Week 0), Week 52

    Change from baseline (week 0) to week 52 in HbA1c is presented. The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above.

Secondary outcomes

  1. Change in Body Weight

    Time frame: Baseline (Week 0), Week 52

    Change from baseline (week 0) to week 52 in body weight is presented. The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above.

  2. 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

    Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was less than (<) 3.0 mmol/L (54 mg/dL) and level 3 had no specific glucose threshold. The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1) last follow-up visit ; 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.

  3. 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

    Time in range was defined as 100 times the number of recorded measurements in glycemic range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive, divided by the total number of recorded measurements. The outcome measure was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct participant-site contact; 2) withdrawal for participants who withdraw their informed consent; 3) the last participant-investigator contact as defined by the investigator for participants who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for participants who die before any of the above.

  4. 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

    Time spent below threshold was defined as 100 times the number of recorded measurements below the threshold, divided by the total number of recorded measurements. The outcome measure was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct participant-site contact; 2) withdrawal for participants who withdraw their informed consent; 3) the last participant-investigator contact as defined by the investigator for participants who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for participants who die before any of the above.

  5. 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

    Time spent above threshold is defined as 100 times the number of recorded measurements above the threshold, divided by the total number of recorded measurements. The outcome measure was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct participant-site contact; 2) withdrawal for participants who withdraw their informed consent; 3) the last participant-investigator contact as defined by the investigator for participants who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for participants who die before any of the above.

  6. Change in Fasting Plasma Glucose (FPG)

    Time frame: Baseline (Week 0), Week 52

    Change in FPG from baseline (week 0) to week 52 is presented. The outcome measure was evaluated based on the data from in study period: Data from randomisation until last date of any of the following: 1) the last direct participant-site contact; 2) withdrawal for participants who withdraw their informed consent; 3) the last participant-investigator contact as defined by the investigator for participants who are lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death for participants who die before any of the above.

  7. Weekly Basal Insulin Dose

    Time frame: From week 50 to week 52

    Estimated mean average weekly basal insulin dose from week 50 to week 52 of treatment is presented. The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1) last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.

  8. 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

    Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was less than (<) 3.0 mmol/L (54 mg/dL). The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1) last follow-up visit ; 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.

  9. Number of Severe Hypoglycaemic Episodes (Level 3)

    Time frame: From baseline week 0 to week 57

    Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 3 had no specific glucose threshold. The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1) last follow-up visit; 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study title

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.

Acronym: COMBINE 1

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Apr 29, 2022
Registry last updated
Dec 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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