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IcoSema

Phase 3

Diabetes Mellitus, Type 2 | Small molecule | Metabolic |Novo Nordisk A/S|Last Updated: Jun 12, 2026

Success Probability

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Trial Design

RandomizedDouble-BlindCONTROLLED
Total Trials4
Total Enrollment2,673

FDA Designations

No designations recorded

Clinical trial landscape

IcoSema · 5 trials · 2 indications

Phase 3 4Phase 1 1
NCT06269107A 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)Type 2 Diabetes
COMPLETED485 Analytics
NCT05352815A 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 IcodecDiabetes Mellitus, Type 2
COMPLETED1,291 Analytics
NCT05259033A 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 Semaglutide (COMBINE 2)Diabetes Mellitus, Type 2
COMPLETED683 Analytics
NCT05013229A 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 Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)Diabetes Mellitus, Type 2
COMPLETED679 Analytics
PHASE3COMPLETED
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)
Type 2 DiabetesUnlock trial analytics
PHASE3COMPLETED
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
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
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 Semaglutide (COMBINE 2)
Diabetes Mellitus, Type 2Unlock trial analytics
PHASE3COMPLETED
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 Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)
Diabetes Mellitus, Type 2Unlock trial analytics

Study Endpoints

Primary Endpoints

Change in glycated haemoglobin (HbA1c)
From baseline (week 0) to week 40

Measured in percentage (%)-point.

Change From Baseline in Glycosylated Haemoglobin (HbA1c)
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.

Change in HbA1c
From baseline week 0 (V2) to week 52 (V54)

Percent-points

AUCIco,0-tz:Area under the serum insulin icodec concentration-time curve after a single dose
From 0 hours to tz hours after IMP administration (day 1) where tz is the time of the last quantifiable concentration

Measured in hours\*pmol/L

Dose-normalised AUCSema,0-tz: Area under the plasma semaglutide concentration-time curve after a single dose divided by dose
From 0 hours to tz hours after IMP administration (day 1) where tz is the time of the last quantifiable concentration

Measured in (hours\*nmol/L)/mg

Secondary Endpoints

Change in body weight
From baseline (week 0) to week 40
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
Time spent less than (<) 3.0 mmol/L (54 mg/dL)
From week 36 to week 40
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
IcoSemaEXPERIMENTALParticipants will receive once weekly IcoSema subcutaneously with or without oral anti diabetic drugs for 40 weeks.
Insulin glargineEXPERIMENTALParticipants will receive once daily insulin glargine subcutaneously with or without oral anti diabetic drugs for 40 weeks.
Insulin icodecACTIVE_COMPARATOR -
SemaglutideEXPERIMENTALParticipants will get once weekly dose
Insuling glargine/insulin aspartACTIVE_COMPARATORParticipants will receive subcutaneous (s.c) injections of insulin glargine once daily combined with 2-4 times daily injections of insulin aspart.
Sequence 1EXPERIMENTALAll participants will get each of the 3 medicines at 3 different timepoints IcoSema - insulin icodec - semaglutide, separated by a 1-4-week wash-out period. The study will last for about 19 to 26 weeks.
Sequence 2EXPERIMENTALAll participants will get each of the 3 medicines at 3 different timepoints IcoSema- semaglutide . insulin icodec, separated by a 1-4-week wash-out period. The study will last for about 19 to 26 weeks.
Sequence 3EXPERIMENTALAll participants will get each of the 3 medicines at 3 different timepoints insulin icodec- IcoSema- semaglutide, separated by a 1-4-week wash-out period. The study will last for about 19 to 26 weeks.
Sequence 4EXPERIMENTALAll participants will get each of the 3 medicines at 3 different timepoints insulin icodec- semaglutide - IcoSema separated by a 1-4-week wash-out period. The study will last for about 19 to 26 weeks.
Sequence 5EXPERIMENTALAll participants will get each of the 3 medicines at 3 different timepoints semaglutide - IcoSema - insulin icodec, separated by a 1-4-week wash-out period. The study will last for about 19 to 26 weeks.
Sequence 6EXPERIMENTALAll participants will get each of the 3 medicines at 3 different timepoints semaglutide - insulin icodec - IcoSema, separated by a 1-4-week wash-out period. The study will last for about 19 to 26 weeks.

Interventions

NameTypeDescription
IcoSemaDRUGIcoSema will be administered subcutaneously.
Insulin glargineDRUGInsulin glargine will be administered subcutaneously.
Insulin icodecDRUGParticipants will receive once weekly Insulin icodec subcutanously (s.c. under the skin) with or without oral anti diabetic drugs for 52 weeks.
Semaglutide 1 mgDRUGSemaglutide once weekly subcutaneously (s.c., under the skin). Dose titrated to 1mg over 8 weeks (0.25 mg for 4 weeks, 0.5 mg for 4 weeks). For about 1 year and 1 month.
insulin aspartDRUGParticipants will receive a once daily subcutaneous (s.c.) injection of insulin glargine combined with Insulin aspart 2-4 times a day during mealtimes for 52 weeks.
semaglutideDRUGOne single dose of semaglutide administered subcutaneously, S.c. into the left thigh
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites118

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 ...

Countries:United StatesChinaGreeceIndiaItalyJapanPolandPuerto RicoSouth AfricaTurkey (Türkiye)AustraliaBelgiumBulgariaCroatiaFinlandMexicoNorwayPortugalRomaniaRussiaSerbiaSouth KoreaTaiwanBrazilCanadaFranceHungaryIsraelSlovakiaSwedenSwitzerlandUkraineCzechiaGermanyMalaysiaSloveniaThailand
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Recent Changes (Last 90 Days)

MEDIUMJul 13, 2026NCT05259033TRIAL_REMOVED: changed
MEDIUMJul 13, 2026NCT05259033TRIAL_REMOVED: changed
MEDIUMJul 13, 2026NCT05259033TRIAL_REMOVED: changed
MEDIUMJul 6, 2026NCT06269107TRIAL_REMOVED: changed
MEDIUMJul 6, 2026NCT06269107TRIAL_REMOVED: changed
MEDIUMJul 6, 2026NCT06269107TRIAL_REMOVED: changed

Frequently asked questions about IcoSema

What is IcoSema used for in Type 2 Diabetes?

IcoSema is an investigational combination of insulin icodec and semaglutide being developed for the treatment of Type 2 Diabetes. It is administered once weekly and is currently in Phase 3 clinical development. IcoSema is not yet approved by regulatory authorities and remains under investigation.

What does IcoSema target?

IcoSema combines insulin icodec, a long-acting insulin analog, with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist. This dual mechanism aims to improve blood sugar control in people with Type 2 Diabetes by addressing both insulin deficiency and incretin effects.

Who makes IcoSema?

IcoSema is being developed by Novo Nordisk A/S, a pharmaceutical company listed on the stock exchange under the ticker NVO. The company is conducting clinical trials to evaluate the safety and efficacy of IcoSema for the treatment of Type 2 Diabetes.

What phase is IcoSema in?

IcoSema is in Phase 3 clinical development for Type 2 Diabetes. It is an investigational drug and has not been approved by the FDA or other regulatory agencies. Four clinical trials have been completed, including three Phase 3 studies and one Phase 1 study.

What clinical trials is IcoSema in?

IcoSema has completed four clinical trials, including three Phase 3 studies: NCT05013229 (COMBINE 3), NCT05259033 (COMBINE 2), and NCT05352815, comparing IcoSema to insulin glargine with insulin aspart, semaglutide, and insulin icodec, respectively. A Phase 1 study, NCT05435677, was conducted in China.

Is IcoSema the same as insulin icodec and semaglutide?

IcoSema is a fixed combination of insulin icodec and semaglutide, but it is not the same as either drug given alone. It is a single weekly medicine that combines both components to control blood sugar in Type 2 Diabetes. Clinical trials have compared IcoSema to each component individually.