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)

NCT06269107 | Completed Phase 3 FDA Drug

• 3 other identifiers: NN1535-4988U1111-1283-86482022-502484-38-00
• Study Type: interventional
• Target: 485
• Locations: 10 countries
• Sites: 100

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).

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change in glycated haemoglobin (HbA1c)

  Measured in percentage (%)-point.

  From baseline (week 0) to week 40

Secondary Outcomes (10)

• 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

• Time spent greater than (>) 10.0 mmol/L (180 mg/dL)

  From week 36 to week 40

• Weekly basal insulin dose

  From week 38 to week 40

Study Arms (2)

IcoSema

EXPERIMENTAL

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

Drug: IcoSema

Insulin glargine

EXPERIMENTAL

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

Drug: Insulin glargine

Interventions

IcoSema DRUG

IcoSema will be administered subcutaneously.

IcoSema

Insulin glargine DRUG

Insulin glargine will be administered subcutaneously.

Insulin glargine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (100)

Scripps Whittier Diabetes Inst

La Jolla, California, 92037, United States

Location

First Valley Med Grp Lancaster

Lancaster, California, 93534, United States

Location

Clinical Trials Research_Sacramento

Lincoln, California, 95821, United States

Location

Desert Oasis Hlthcr Med Group

Palm Springs, California, 91355, United States

Location

Desert Oasis Hlthcr Med Group

Palm Springs, California, 92262, United States

Location

Northeast Research Institute

Fleming Island, Florida, 32003, United States

Location

Clinical Research of Cent FL

Winter Haven, Florida, 33880, United States

Location

Atlanta Diabetes Associates

Atlanta, Georgia, 30318, United States

Location

Endo Res Solutions Inc

Roswell, Georgia, 30076, United States

Location

Elite Clinical Trials

Blackfoot, Idaho, 83221, United States

Location

Cedar-Crosse Research Center

Chicago, Illinois, 60607, United States

Location

Endeavor Health

Skokie, Illinois, 60077, United States

Location

Cotton-O'Neil Diab & Endo Ctr

Topeka, Kansas, 66606, United States

Location

Methodist Phys. Clinic

Omaha, Nebraska, 68114, United States

Location

Albuquerque Clin Trials, Inc.

Albuquerque, New Mexico, 87102, United States

Location

AMC Community Endocrinology

Albany, New York, 12203, United States

Location

Southgate Medical Group, LLP

West Seneca, New York, 14224, United States

Location

Physician's East Endocrinology

Greenville, North Carolina, 27834, United States

Location

Diab & Endo Assoc of Stark Co

Canton, Ohio, 44718, United States

Location

Advanced Medical Research

Maumee, Ohio, 43537, United States

Location

New Venture Medical Research

Wadsworth, Ohio, 44281-9236, United States

Location

Holston Medical Group

Kingsport, Tennessee, 37660, United States

Location

Amarillo Med Spec LLP

Amarillo, Texas, 79106, United States

Location

Velocity Clinical Research- Cedar Park

Austin, Texas, 78759, United States

Location

Velocity Clinical Res-Dallas

Dallas, Texas, 75230, United States

Location

North Texas Endocrine Center

Dallas, Texas, 75231, United States

Location

Diabetes and Thyroid Ctr of FW

Fort Worth, Texas, 76132, United States

Location

Fmc Science, Llc

Lampasas, Texas, 76550, United States

Location

Quality Research Inc

San Antonio, Texas, 78209, United States

Location

Flourish Research

San Antonio, Texas, 78229, United States

Location

Consano Clinical Research, LLC

Shavano Park, Texas, 78231, United States

Location

Wade Family Medicine

Bountiful, Utah, 84010, United States

Location

TPMG Clinical Research

Newport News, Virginia, 23606, United States

Location

Peking University People's Hospital-Endocrinology

Beijing, Beijing Municipality, 100044, China

Location

Beijing Friendship Hospital, Capital Medical University-Endocrinology

Beijing, Beijing Municipality, 100050, China

Location

Chongqing University Three Gorges Hospital

Chongqing, Chongqing Municipality, 404000, China

Location

Huizhou Central People's Hospital-Endocrinology

Huizhou, Guangdong, 516001, China

Location

The Second Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210011, China

Location

The Affiliated Hospital of Jiangsu University

Zhenjiang, Jiangsu, 212001, China

Location

Jinan Central Hospital

Jinan, Shandong, 250013, China

Location

Shanghai Pudong New Area People's Hospital-Endocrinology

Shanghai, Shanghai Municipality, 201200, China

Location

Evangelismos Hospital

Athens, 10676, Greece

Location

'G. Gennimatas' General Hospital of Athens

Athens, 115 27, Greece

Location

"Laiko" General Hospital of Athens

Athens, 11527, Greece

Location

General Hospital of Kalamata - B Internal Medicine Department

Kalamata, 24100, Greece

Location

Univ Gen Hospital Larisa

Larissa, 41110, Greece

Location

"Thermi" Private Hosital

Thessaloniki, 57001, Greece

Location

Ramaiah Memorial Hospital

Bangalore, Karnataka, 560054, India

Location

Mysore Medical College and Research Institute

Mysore, Karnataka, 570001, India

Location

BYL Nair Hospital and T N Medical College Department of endo

Mumbai, Maharashtra, 400008, India

Location

Seth GS Medical College & KEM Hospital

Mumbai, Maharashtra, 400012, India

Location

BSES MG hospital

Mumbai, Maharashtra, 400058, India

Location

Chellaram Diabetes Institute

Pune, Maharashtra, 411021, India

Location

SMS Medical College & Hospital

Jaipur, Rajasthan, 302004, India

Location

Diabetes, Thyroid and Endocrine Centre

Jaipur, Rajasthan, 302006, India

Location

Madras Diabetes Research Foundation

Chennai, Tamil Nadu, 600086, India

Location

Udyaan Health Care

Lucknow, Uttar Pradesh, 226002, India

Location

Post Graduate Institute of Medical Education & Research

Chandigarh, 160012, India

Location

IPGME&R and SSKM Hospital

Kolkata, 700020, India

Location

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

L’Aquila, Abbruzzo, 67100, Italy

Location

Casa Sollievo della Sofferenza reparto endocrinologia

San Giovanni Rotondo, FG, 71013, Italy

Location

A.O.U. Policlinico Umberto I

Rome, Lazio, 00161, Italy

Location

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

Ancona, 60127, Italy

Location

Casa della Salute di Ceccano - Ambulatori Campus Biomedico

Ceccano (Frosinone), 03023, Italy

Location

Polo Ospedaliero di Chiavari

Chiavari (genova), 16043, Italy

Location

Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

Azienda Ospedaliera di Perugia;Ospedale S. Maria della Misericordia

Perugia, 06129, Italy

Location

Heiwadai Hospital_Internal Medicine

Miyazaki, Miyazaki, 880-0034, Japan

Location

Tokuyama clinic_Diabetic internal medicine

Chiba, 261-0004, Japan

Location

Oodouri Diabetes, Internal medicine Clinic_Internal Medicine, Diabetes Internal Medicine

Hokkaido, 060-0001, Japan

Location

Oyama East Clinic_Internal Medicine

Tochigi, 323-0022, Japan

Location

Tokyo-Eki Center-building Clinic_Internal Medicine

Tokyo, 103-0027, Japan

Location

Fukuwa Clinic_Internal Medicine

Tokyo, 104-0031, Japan

Location

Juntendo University Hospital_Diabetes, endocrinology and metabolism

Tokyo, 113-8431, Japan

Location

NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska

Bialystok, Podlaskie Voivodeship, 15-435, Poland

Location

SNZOZ Lege Artis

Bialystok, 15-404, Poland

Location

Uniwersyteckie Centrum Kliniczne Regionalne Centrum Diabetologii

Gdansk, 80-214, Poland

Location

Grazyna Pulka Specjalistyczny Osrodek "All-Med"

Krakow, 30-033, Poland

Location

Gabinet Lekarski Malgorzata Saryusz-Wolska

Lodz, 90-132, Poland

Location

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

Lodz, 90-338, Poland

Location

Velocity Nova Sp. z o.o.

Lublin, 20-362, Poland

Location

NBR Polska Tomasz Klodawski

Warsaw, 00-710, Poland

Location

PANSTWOWY INSTYTUT MEDYCZNY MSWiA

Warsaw, 02-507, Poland

Location

Clinhouse Centrum Medyczne

Zabrze, 41-807, Poland

Location

Velocity Nova Sp. z o.o.

Staszów, Świętokrzyskie Voivodeship, 28-200, Poland

Location

Advanced Clinical Research LLC

Bayamón, 00959, Puerto Rico

Location

Dr R Dulabh

Johannesburg, Gauteng, 1812, South Africa

Location

Newtown Clinical Research

Johannesburg, Gauteng, 2001, South Africa

Location

Roodepoort Medicross Clinical Research Centre

Roodepoort, Gauteng, 1724, South Africa

Location

Dr Pillay's Rooms

Durban, KwaZulu-Natal, 4450, South Africa

Location

Clinical Research Institute of South Africa

KwaDukuza, KwaZulu-Natal, 4449, South Africa

Location

Langeberg Clinical Trials

Cape Town, Western Cape, 7572, South Africa

Location

Akdeniz University Tip Fakultesi Hastanesi

Antalya, 07058, Turkey (Türkiye)

Location

Akdeniz Üniversitesi Hastanesi- Endokrinoloji

Antalya, 07058, Turkey (Türkiye)

Location

Seyrantepe Hamidiye Etfal Egitim ve Arastirma Hastanesi

Istanbul, 34371, Turkey (Türkiye)

Location

Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi- Seyrantepe Yerleşkesi- Endokrinoloji

Istanbul, 34371, Turkey (Türkiye)

Location

İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Endokrinoloji

Istanbul, 34390, Turkey (Türkiye)

Location

Başakşehir Çam ve Sakura Şehir Hastanesi

Istanbul, 34480, Turkey (Türkiye)

Location

T.C. Saglik Bakanligi Pendik Egitim ve Arastirma Hastanesi

Istanbul, 34899, Turkey (Türkiye)

Location

Tekirdağ Namık Kemal Üniversitesi Hastanesi- Dahiliye

Tekirdağ, 59030, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin Glargine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Clinical Transparency (dept. 2834)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2024
• First Posted: February 21, 2024
• Study Start: February 15, 2024
• Primary Completion: May 27, 2025
• Study Completion: July 8, 2025
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (8); PR (1); ZA (6); TU (8); PL (11); IT (8); JP (7); GR (6); IN (12); US (33)