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)

NCT ID: NCT06269107

Last Updated: 2025-09-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

485 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-15

Study Completion Date

2025-07-08

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Type 2 Diabetes

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

IcoSema

Participants will receive once weekly IcoSema subcutaneously with or without oral anti diabetic drugs for 40 weeks.

Group Type EXPERIMENTAL

IcoSema

Intervention Type DRUG

IcoSema will be administered subcutaneously.

Insulin glargine

Participants will receive once daily insulin glargine subcutaneously with or without oral anti diabetic drugs for 40 weeks.

Group Type EXPERIMENTAL

Insulin glargine

Intervention Type DRUG

Insulin glargine will be administered subcutaneously.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

IcoSema

IcoSema will be administered subcutaneously.

Intervention Type DRUG

Insulin glargine

Insulin glargine will be administered subcutaneously.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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).

* 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.

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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Novo Nordisk A/S

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Clinical Transparency (dept. 2834)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Scripps Whittier Diabetes Inst

La Jolla, California, United States

Site Status

First Valley Med Grp Lancaster

Lancaster, California, United States

Site Status

Desert Oasis Hlthcr Med Group

Palm Springs, California, United States

Site Status

Desert Oasis Hlthcr Med Group

Palm Springs, California, United States

Site Status

Clinical Trials Research_Sacramento

Sacramento, California, United States

Site Status

Northeast Research Institute

Fleming Island, Florida, United States

Site Status

Clinical Research of Cent FL

Winter Haven, Florida, United States

Site Status

Atlanta Diabetes Associates

Atlanta, Georgia, United States

Site Status

Elite Clinical Trials

Blackfoot, Idaho, United States

Site Status

Cedar-Crosse Research Center

Chicago, Illinois, United States

Site Status

Endeavor Health

Skokie, Illinois, United States

Site Status

Cotton-O'Neil Diab & Endo Ctr

Topeka, Kansas, United States

Site Status

Methodist Phys. Clinic

Omaha, Nebraska, United States

Site Status

Albuquerque Clin Trials, Inc.

Albuquerque, New Mexico, United States

Site Status

AMC Community Endocrinology

Albany, New York, United States

Site Status

Southgate Medical Group, LLP

West Seneca, New York, United States

Site Status

Physician's East Endocrinology

Greenville, North Carolina, United States

Site Status

Diab & Endo Assoc of Stark Co

Canton, Ohio, United States

Site Status

Advanced Medical Research

Maumee, Ohio, United States

Site Status

New Venture Medical Research

Wadsworth, Ohio, United States

Site Status

Amarillo Med Spec LLP

Amarillo, Texas, United States

Site Status

Velocity Clinical Research- Cedar Park

Austin, Texas, United States

Site Status

Velocity Clinical Res-Dallas

Dallas, Texas, United States

Site Status

North Texas Endocrine Center

Dallas, Texas, United States

Site Status

Diabetes and Thyroid Ctr of FW

Fort Worth, Texas, United States

Site Status

Fmc Science, Llc

Lampasas, Texas, United States

Site Status

Quality Research Inc

San Antonio, Texas, United States

Site Status

Flourish Research

San Antonio, Texas, United States

Site Status

Consano Clinical Research, LLC

Shavano Park, Texas, United States

Site Status

TPMG Clinical Research

Newport News, Virginia, United States

Site Status

Peking University People's Hospital-Endocrinology

Beijing, Beijing Municipality, China

Site Status

Beijing Friendship Hospital, Capital Medical University-Endocrinology

Beijing, Beijing Municipality, China

Site Status

Chongqing University Three Gorges Hospital

Chongqing, Chongqing Municipality, China

Site Status

Huizhou Central People's Hospital-Endocrinology

Huizhou, Guangdong, China

Site Status

The Second Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Site Status

The Affiliated Hospital of Jiangsu University

Zhenjiang, Jiangsu, China

Site Status

Jinan Central Hospital Affiliated to Shandong University

Jinan, Shandong, China

Site Status

Jinan Central Hospital

Jinan, Shandong, China

Site Status

Shanghai Pudong New Area People's Hospital-Endocrinology

Shanghai, Shanghai Municipality, China

Site Status

Evangelismos Hospital

Athens, , Greece

Site Status

'G. Gennimatas' General Hospital of Athens

Athens, , Greece

Site Status

"Laiko" General Hospital of Athens

Athens, , Greece

Site Status

General Hospital of Kalamata

Kalamata, , Greece

Site Status

Univ Gen Hospital Larisa

Larissa, , Greece

Site Status

"Thermi" Private Hosital

Thessaloniki, , Greece

Site Status

Ramaiah Memorial Hospital

Bangalore, Karnataka, India

Site Status

Mysore Medical College and Research Institute

Mysore, Karnataka, India

Site Status

BYL Nair Hospital and T N Medical College Department of endo

Mumbai, Maharashtra, India

Site Status

Seth GS Medical College & KEM Hospital

Mumbai, Maharashtra, India

Site Status

BSES MG hospital

Mumbai, Maharashtra, India

Site Status

Chellaram Diabetes Institute

Pune, Maharashtra, India

Site Status

SMS Medical College & Hospital

Jaipur, Rajasthan, India

Site Status

Diabetes, Thyroid and Endocrine Centre

Jaipur, Rajasthan, India

Site Status

Madras Diabetes Research Foundation

Chennai, Tamil Nadu, India

Site Status

Udyaan Health Care

Lucknow, Uttar Pradesh, India

Site Status

Post Graduate Institute of Medical Education & Research

Chandigarh, , India

Site Status

ASL Avezzano Sulmona L'Aquila - Ospedale San Salvatore - UOC Diabetologia

L’Aquila, Abbruzzo, Italy

Site Status

Casa Sollievo della Sofferenza reparto endocrinologia

San Giovanni Rotondo, FG, Italy

Site Status

A.O.U. Policlinico Umberto I

Rome, Lazio, Italy

Site Status

I.N.R.C.A. Istituto Nazionale di Riposo E Cura Per Gli Anziani

Ancona, , Italy

Site Status

Casa della Salute di Ceccano - Ambulatori Campus Biomedico

Ceccano (Frosinone), , Italy

Site Status

ASL 4 Chiavarese

Chiavari (genova), , Italy

Site Status

Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status

Azienda Ospedaliera di Perugia;Ospedale S. Maria della Misericordia

Perugia, , Italy

Site Status

Heiwadai Hospital_Internal Medicine

Miyazaki, Miyazaki, Japan

Site Status

Tokuyama clinic_Diabetic internal medicine

Chiba, , Japan

Site Status

Oodouri Diabetes, Internal medicine Clinic_Internal Medicine, Diabetes Internal Medicine

Hokkaido, , Japan

Site Status

Oyama East Clinic_Internal Medicine

Tochigi, , Japan

Site Status

Tokyo-Eki Center-building Clinic_Internal Medicine

Tokyo, , Japan

Site Status

Fukuwa Clinic_Internal Medicine

Tokyo, , Japan

Site Status

Juntendo University Hospital

Tokyo, , Japan

Site Status

NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska

Bialystok, Podlaskie Voivodeship, Poland

Site Status

SNZOZ Lege Artis

Bialystok, , Poland

Site Status

Grazyna Pulka Specjalistyczny Osrodek "All-Med"

Krakow, , Poland

Site Status

Gabinet Lekarski Malgorzata Saryusz-Wolska

Lodz, , Poland

Site Status

Centrum Terapii Współczesnej J.M. Jasnorzewska S.K.A.

Lodz, , Poland

Site Status

Velocity Nova Sp. z o.o.

Lublin, , Poland

Site Status

NBR Polska Tomasz Klodawski

Warsaw, , Poland

Site Status

PANSTWOWY INSTYTUT MEDYCZNY MSWiA

Warsaw, , Poland

Site Status

Clinhouse Centrum Medyczne

Zabrze, , Poland

Site Status

Velocity Nova Sp. z o.o.

Staszów, Świętokrzyskie Voivodeship, Poland

Site Status

Advanced Clinical Research LLC

Bayamón, , Puerto Rico

Site Status

Dr R Dulabh

Johannesburg, Gauteng, South Africa

Site Status

Newtown Clinical Research

Johannesburg, Gauteng, South Africa

Site Status

Roodepoort Medicross Clinical Research Centre

Roodepoort, Gauteng, South Africa

Site Status

Dr Pillay's Rooms

Durban, KwaZulu-Natal, South Africa

Site Status

Clinical Research Institute of South Africa

KwaDukuza, KwaZulu-Natal, South Africa

Site Status

Langeberg Clinical Trials

Cape Town, Western Cape, South Africa

Site Status

Akdeniz University Tip Fakultesi Hastanesi

Antalya, , Turkey (Türkiye)

Site Status

Seyrantepe Hamidiye Etfal Egitim ve Arastirma Hastanesi

Istanbul, , Turkey (Türkiye)

Site Status

T.C. Saglik Bakanligi Pendik Egitim ve Arastirma Hastanesi

Istanbul, , Turkey (Türkiye)

Site Status

Tekirdag Namık Kemal UTF

Tekirdağ, , Turkey (Türkiye)

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States China Greece India Italy Japan Poland Puerto Rico South Africa Turkey (Türkiye)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

U1111-1283-8648

Identifier Type: OTHER

Identifier Source: secondary_id

2022-502484-38-00

Identifier Type: OTHER

Identifier Source: secondary_id

NN1535-4988

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.