NCT06269107CompletedPhase 3
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)
A 40-week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Daily Insulin Glargine 100 Units/mL in Participants With Type 2 Diabetes Inadequately Controlled on Oral Anti Diabetic Drugs COMBINE 4
Source: ClinicalTrials.gov · Last updated 5 Jun 2026
Brief summary (registry, in English)
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).
- Status (registry)
- Completed
- Phase (registry)
- Phase 3
- Study type
- Interventional
- Enrollment
- 485 (actual)
- First submitted
- 13 Feb 2024
- Start date
- 15 Feb 2024
- Primary completion date
- 27 May 2025
- Lead sponsor
- Novo Nordisk A/S
- Diseases
- Type 2 diabetes
- NCT number
- NCT06269107
- EU CT number
- 2022-502484-38-00
What you commit to
- Study type: Interventional · Phase 3
- Participants enrolled: 485
- From 15 Feb 2024 to the primary completion date, 27 May 2025
- 114 sites in 10 countries
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- 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.
- 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.
Other illness
- Chronic heart failure classified as being in New York Heart Association Class IV at screening.
Lab values
- 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).
Other
- Female who is pregnant, breast-feeding or intends to become pregnant or is of childbaring potential and not using highly effective contraceptive method.
- Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.
Who the study is looking for
- 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).
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
Sites (114)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Beijing Friendship Hospital, Capital Medical University-Endocrinology Coordinator of this site? Confirm its status | Beijing | China | Unknown status |
| Peking University People's Hospital-Endocrinology Coordinator of this site? Confirm its status | Beijing | China | Unknown status |
| Chongqing University Three Gorges Hospital Coordinator of this site? Confirm its status | Chongqing | China | Unknown status |
| Hengshui People's Hospital (Harrison International Peace Hospital)-Endocrinology Coordinator of this site? Confirm its status | Hengshui | China | Unknown status |
| Huizhou Central People's Hospital-Endocrinology Coordinator of this site? Confirm its status | Huizhou | China | Unknown status |
| Jinan Central Hospital Coordinator of this site? Confirm its status | Jinan | China | Unknown status |
| The Second Affiliated Hospital of Nanjing Medical University Coordinator of this site? Confirm its status | Nanjing | China | Unknown status |
| Shanghai Pudong New Area People's Hospital-Endocrinology Coordinator of this site? Confirm its status | Shanghai | China | Unknown status |
| The Affiliated Hospital of Jiangsu University Coordinator of this site? Confirm its status | Zhenjiang | China | Unknown status |
| Laiko General Hospital of Athens Coordinator of this site? Confirm its status | Athens | Greece | Completed |
| Evangelismos S A Coordinator of this site? Confirm its status | Athens | Greece | Completed |
| General Hospital of Athens "G. Gennimatas" Coordinator of this site? Confirm its status | Athens | Greece | Completed |
| General Hospital Of Messinia Coordinator of this site? Confirm its status | Kalamata | Greece | Completed |
| General University Hospital of Larissa Coordinator of this site? Confirm its status | Larissa | Greece | Completed |
| Thermi Clinic S.A. Coordinator of this site? Confirm its status | Thessaloniki | Greece | Completed |
| Ramaiah Memorial Hospital Coordinator of this site? Confirm its status | Bangalore | India | Unknown status |
| Sai A Health Wellness LLP Coordinator of this site? Confirm its status | Bangalore | India | Unknown status |
| Post Graduate Institute of Medical Education & Research, Coordinator of this site? Confirm its status | Chandigarh | India | Unknown status |
| Madras Diabetes Research Foundation Coordinator of this site? Confirm its status | Chennai | India | Unknown status |
| Goa Medical College Coordinator of this site? Confirm its status | Goa | India | Unknown status |
| CHL Hospitals Coordinator of this site? Confirm its status | Indore | India | Unknown status |
| Diabetes, Thyroid and Endocrine Centre Coordinator of this site? Confirm its status | Jaipur | India | Unknown status |
| SMS Medical College & Hospital Coordinator of this site? Confirm its status | Jaipur | India | Unknown status |
| IPGME&R and SSKM Hospital Coordinator of this site? Confirm its status | Kolkata | India | Unknown status |
| METTA Clinic (a unit of Healious Global Pvt. Ltd.) Coordinator of this site? Confirm its status | Kolkata | India | Unknown status |
| Udyaan Health Care Coordinator of this site? Confirm its status | Lucknow | India | Unknown status |
| BYL Nair Hospital and T N Medical College Department of endo Coordinator of this site? Confirm its status | Mumbai | India | Unknown status |
| BSES MG hospital Coordinator of this site? Confirm its status | Mumbai | India | Unknown status |
| Seth GS Medical College & KEM Hospital Coordinator of this site? Confirm its status | Mumbai | India | Unknown status |
| Mysore Medical College and Research Institute Coordinator of this site? Confirm its status | Mysore | India | Unknown status |
| Chellaram Diabetes Institute Coordinator of this site? Confirm its status | Pune | India | Unknown status |
| I.N.R.C.A. Istituto Nazionale di Riposo E Cura Per Gli Anziani Coordinator of this site? Confirm its status | Ancona | Italy | Completed |
| Casa della Salute Coordinator of this site? Confirm its status | Ceccano, (FR) | Italy | Completed |
| Azienda Sociosanitaria Ligure N 4 Sistema Sanitario Regione Liguria Coordinator of this site? Confirm its status | Chiavari | Italy | Completed |
| ASL1 Abruzzo, Dipartimento Medico, Ospedale San Salvatore Coordinator of this site? Confirm its status | L'Aquila | Italy | Completed |
| ASST Grande Ospedale Metropolitano Niguarda Coordinator of this site? Confirm its status | Milan | Italy | Completed |
| Hospital Santa Maria Della Misericordia Coordinator of this site? Confirm its status | Perugia | Italy | Completed |
| Azienda Ospealiero Universitaria Policlinico Umberto I Coordinator of this site? Confirm its status | Rome | Italy | Completed |
| Casa Sollievo della Sofferenza Coordinator of this site? Confirm its status | San Giovanni Rotondo | Italy | Completed |
| Tokuyama clinic_Diabetic internal medicine Coordinator of this site? Confirm its status | Chiba | Japan | Unknown status |
| Oodouri Diabetes, Internal medicine Clinic_Internal Medicine, Diabetes Internal Medicine Coordinator of this site? Confirm its status | Hokkaido | Japan | Unknown status |
| Heiwadai Hospital_Internal Medicine Coordinator of this site? Confirm its status | Miyazaki | Japan | Unknown status |
| Oyama East Clinic_Internal Medicine Coordinator of this site? Confirm its status | Tochigi | Japan | Unknown status |
| Fukuwa Clinic_Internal Medicine Coordinator of this site? Confirm its status | Tokyo | Japan | Unknown status |
| Tokyo-Eki Center-building Clinic_Internal Medicine Coordinator of this site? Confirm its status | Tokyo | Japan | Unknown status |
| Juntendo University Hospital_Diabetes, endocrinology and metabolism Coordinator of this site? Confirm its status | Tokyo | Japan | Unknown status |
| Legeartis Poradnie Specjalistyczne Sp. z o.o. Coordinator of this site? Confirm its status | Bialystok | Poland | Completed |
| Nzoz Specjalistyczny Osrodek Internistyczno-Diabetologiczny Malgorzata Arciszewska Coordinator of this site? Confirm its status | Bialystok | Poland | Completed |
| Centrum Medyczne All-Med Badania Kliniczne Coordinator of this site? Confirm its status | Cracow | Poland | Completed |
| Uniwersyteckie Centrum Kliniczne Coordinator of this site? Confirm its status | Gdansk | Poland | Completed |
| Gabinet Lekarski Malgorzata Saryusz-Wolska Coordinator of this site? Confirm its status | Lodz | Poland | Completed |
| Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A. Coordinator of this site? Confirm its status | Lodz | Poland | Completed |
| Velocity Nova Sp. z o.o. Coordinator of this site? Confirm its status | Lublin | Poland | Completed |
| Velocity Nova Sp. z o.o. Coordinator of this site? Confirm its status | Staszow | Poland | Completed |
| Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych i Administracji Coordinator of this site? Confirm its status | Warsaw | Poland | Completed |
| NBR POLSKA TOMASZ KLODAWSKI Coordinator of this site? Confirm its status | Warszawa | Poland | Completed |
| Clinhouse Sp. z o.o. Coordinator of this site? Confirm its status | Zabrze | Poland | Completed |
| Advanced Clinical Research, LLC Coordinator of this site? Confirm its status | Bayamón | Puerto Rico | Unknown status |
| AMC Community Endocrinology Coordinator of this site? Confirm its status | Albany | United States | Unknown status |
| Albuquerque Clin Trials, Inc. Coordinator of this site? Confirm its status | Albuquerque | United States | Unknown status |
| Amarillo Med Spec LLP Coordinator of this site? Confirm its status | Amarillo | United States | Unknown status |
| Atlanta Diabetes Associates Coordinator of this site? Confirm its status | Atlanta | United States | Unknown status |
| Velocity Clinical Research- Cedar Park Coordinator of this site? Confirm its status | Austin | United States | Unknown status |
| Univ of Alabama Birmingham Coordinator of this site? Confirm its status | Birmingham | United States | Unknown status |
| Elite Clinical Trials Coordinator of this site? Confirm its status | Blackfoot | United States | Unknown status |
| Wade Family Medicine Coordinator of this site? Confirm its status | Bountiful | United States | Unknown status |
| Diab & Endo Assoc of Stark Co Coordinator of this site? Confirm its status | Canton | United States | Unknown status |
| Cedar Crosse Research Center Coordinator of this site? Confirm its status | Chicago | United States | Unknown status |
| John Muir Physicians Network Coordinator of this site? Confirm its status | Concord | United States | Unknown status |
| Velocity Clinical Res-Dallas Coordinator of this site? Confirm its status | Dallas | United States | Unknown status |
| North Texas Endocrine Center Coordinator of this site? Confirm its status | Dallas | United States | Unknown status |
| Northeast Research Institute Coordinator of this site? Confirm its status | Fleming Island | United States | Unknown status |
| Diabetes and Thyroid Ctr of FW Coordinator of this site? Confirm its status | Fort Worth | United States | Unknown status |
| PharmQuest Life Sciences LLC Coordinator of this site? Confirm its status | Greensboro | United States | Unknown status |
| Physician's East Endocrinology Coordinator of this site? Confirm its status | Greenville | United States | Unknown status |
| East West Medical Research Institute_Honolulu Coordinator of this site? Confirm its status | Honolulu | United States | Unknown status |
| East Coast Institute for Research Coordinator of this site? Confirm its status | Jacksonville | United States | Unknown status |
| Holston Medical Group. Coordinator of this site? Confirm its status | Kingsport | United States | Unknown status |
| Scripps Whittier Diabetes Inst Coordinator of this site? Confirm its status | La Jolla | United States | Unknown status |
| Fmc Science, Llc Coordinator of this site? Confirm its status | Lampasas | United States | Unknown status |
| First Valley Med Grp Lancaster Coordinator of this site? Confirm its status | Lancaster | United States | Unknown status |
| The Research Group of Lexington LLC Coordinator of this site? Confirm its status | Lexington | United States | Unknown status |
| Clinical Trials Research_Sacramento Coordinator of this site? Confirm its status | Lincoln | United States | Unknown status |
| Advanced Medical Research Coordinator of this site? Confirm its status | Maumee | United States | Unknown status |
| TPMG Clinical Research Coordinator of this site? Confirm its status | Newport News | United States | Unknown status |
| Methodist Phys. Clinic Coordinator of this site? Confirm its status | Omaha | United States | Unknown status |
| Desert Oasis Hlthcr Med Group Coordinator of this site? Confirm its status | Palm Springs | United States | Unknown status |
| Epic Medical Research Coordinator of this site? Confirm its status | Red Oak | United States | Unknown status |
| Endo and Metab Consultants Coordinator of this site? Confirm its status | Rockville | United States | Unknown status |
| Endo Res Solutions Inc Coordinator of this site? Confirm its status | Roswell | United States | Unknown status |
| Flourish Research Coordinator of this site? Confirm its status | San Antonio | United States | Unknown status |
| Quality Research Inc Coordinator of this site? Confirm its status | San Antonio | United States | Unknown status |
| Consano Clinical Research, LLC Coordinator of this site? Confirm its status | Shavano Park | United States | Unknown status |
| Endeavor Health Coordinator of this site? Confirm its status | Skokie | United States | Unknown status |
| Simcare Medical Research, LLC Coordinator of this site? Confirm its status | Sugar Land | United States | Unknown status |
| Cotton O'Neil Diab & Endo Ctr Coordinator of this site? Confirm its status | Topeka | United States | Unknown status |
| Essential Medical Research LLC Coordinator of this site? Confirm its status | Tulsa | United States | Unknown status |
| New Venture Medical Research Coordinator of this site? Confirm its status | Wadsworth | United States | Unknown status |
| Southgate Medical Group, LLP Coordinator of this site? Confirm its status | West Seneca | United States | Unknown status |
| Clinical Research of Cent FL Coordinator of this site? Confirm its status | Winter Haven | United States | Unknown status |
| Langeberg Clinical Trials Coordinator of this site? Confirm its status | Cape Town | South Africa | Unknown status |
| Dr Pillay's Rooms Coordinator of this site? Confirm its status | Durban | South Africa | Unknown status |
| Newtown Clinical Research Coordinator of this site? Confirm its status | Johannesburg | South Africa | Unknown status |
| Dr R Dulabh Coordinator of this site? Confirm its status | Johannesburg | South Africa | Unknown status |
| Clinical Research Institute of South Africa Coordinator of this site? Confirm its status | KwaDukuza | South Africa | Unknown status |
| Roodepoort Medicross Clinical Research Centre Coordinator of this site? Confirm its status | Roodepoort | South Africa | Unknown status |
| Akdeniz Üniversitesi Hastanesi- Endokrinoloji Coordinator of this site? Confirm its status | Antalya | Turkey (Türkiye) | Unknown status |
| Akdeniz University Tip Fakultesi Hastanesi Coordinator of this site? Confirm its status | Antalya | Turkey (Türkiye) | Unknown status |
| Seyrantepe Hamidiye Etfal Egitim ve Arastirma Hastanesi Coordinator of this site? Confirm its status | Istanbul | Turkey (Türkiye) | Unknown status |
| İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Endokrinoloji Coordinator of this site? Confirm its status | Istanbul | Turkey (Türkiye) | Unknown status |
| Başakşehir Çam ve Sakura Şehir Hastanesi Coordinator of this site? Confirm its status | Istanbul | Turkey (Türkiye) | Unknown status |
| Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi- Seyrantepe Yerleşkesi- Endokrinoloji Coordinator of this site? Confirm its status | Istanbul | Turkey (Türkiye) | Unknown status |
| T.C. Saglik Bakanligi Pendik Egitim ve Arastirma Hastanesi Coordinator of this site? Confirm its status | Istanbul | Turkey (Türkiye) | Unknown status |
| Tekirdağ Namık Kemal Üniversitesi Hastanesi- Dahiliye Coordinator of this site? Confirm its status | Tekirdağ | Turkey (Türkiye) | Unknown status |
Related publications
- Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.Lancet Diabetes Endocrinol · 2026 · PMID 42594928
This page is information, not medical advice. Discuss any trial with your doctor.