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) (COMBINE 4)

June 4, 2026 updated by: Novo Nordisk A/S

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

485

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100044
        • Peking University People's Hospital-Endocrinology
      • Beijing, Beijing Municipality, China, 100050
        • Beijing Friendship Hospital, Capital Medical University-Endocrinology
    • Chongqing Municipality
      • Chongqing, Chongqing Municipality, China, 404000
        • Chongqing University Three Gorges Hospital
    • Guangdong
      • Huizhou, Guangdong, China, 516001
        • Huizhou Central People's Hospital-Endocrinology
    • Hebei
      • Hengshui, Hebei, China, 053000
        • Hengshui People's Hospital (Harrison International Peace Hospital)-Endocrinology
    • Jiangsu
      • Nanjing, Jiangsu, China, 210011
        • The Second Affiliated Hospital of Nanjing Medical University
      • Zhenjiang, Jiangsu, China, 212001
        • The Affiliated Hospital of Jiangsu University
    • Shandong
      • Jinan, Shandong, China, 250013
        • Jinan Central Hospital
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 201200
        • Shanghai Pudong New Area People's Hospital-Endocrinology
  • Greece
      • Athens, Greece, 11527
        • "Laiko" General Hospital of Athens
      • Athens, Greece, 10676
        • Evangelismos Hospital
      • Athens, Greece, 115 27
        • 'G. Gennimatas' General Hospital of Athens
      • Kalamata, Greece, 24100
        • General Hospital of Kalamata - B Internal Medicine Department
      • Larissa, Greece, 41110
        • Univ Gen Hospital Larisa
      • Thessaloniki, Greece, 57001
        • "Thermi" Private Hosital
  • India
      • Chandigarh, India, 160012
        • Post Graduate Institute of Medical Education & Research
      • Kolkata, India, 700039
        • METTA Clinic (a unit of Healious Global Pvt. Ltd.)
      • Kolkata, India, 700020
        • IPGME&R and SSKM Hospital
    • Karnataka
      • Bangalore, Karnataka, India, 560054
        • Ramaiah Memorial Hospital
      • Bangalore, Karnataka, India, 560080
        • Sai A Health Wellness LLP
      • Mysore, Karnataka, India, 570001
        • Mysore Medical College and Research Institute
    • Madhya Pradesh
      • Indore, Madhya Pradesh, India, 452008
        • CHL Hospitals
    • Maharashtra
      • Goa, Maharashtra, India, 403 202
        • Goa Medical College
      • Mumbai, Maharashtra, India, 400058
        • BSES MG hospital
      • Mumbai, Maharashtra, India, 400008
        • BYL Nair Hospital and T N Medical College Department of endo
      • Mumbai, Maharashtra, India, 400012
        • Seth GS Medical College & KEM Hospital
      • Pune, Maharashtra, India, 411021
        • Chellaram Diabetes Institute
    • Rajasthan
      • Jaipur, Rajasthan, India, 302004
        • SMS Medical College & Hospital
      • Jaipur, Rajasthan, India, 302006
        • Diabetes, Thyroid and Endocrine Centre
    • Tamil Nadu
      • Chennai, Tamil Nadu, India, 600086
        • Madras Diabetes Research Foundation
    • Uttar Pradesh
      • Lucknow, Uttar Pradesh, India, 226002
        • Udyaan Health Care
  • Italy
      • Ancona, Italy, 60127
        • I.N.R.C.A. Istituto Nazionale di Riposo E Cura Per Gli Anziani
      • Ceccano (Frosinone), Italy, 03023
        • Casa della Salute di Ceccano - Ambulatori Campus Biomedico
      • Chiavari (genova), Italy, 16043
        • Polo Ospedaliero di Chiavari
      • Milan, Italy, 20162
        • Grande Ospedale Metropolitano Niguarda
      • Perugia, Italy, 06129
        • Azienda Ospedaliera di Perugia;Ospedale S. Maria della Misericordia
    • Abbruzzo
      • L’Aquila, Abbruzzo, Italy, 67100
        • ASL Avezzano Sulmona L'Aquila - Ospedale San Salvatore - UOC Diabetologia
    • FG
      • San Giovanni Rotondo, FG, Italy, 71013
        • Casa Sollievo della Sofferenza reparto endocrinologia
    • Lazio
      • Rome, Lazio, Italy, 00161
        • A.O.U. Policlinico Umberto I
  • Japan
      • Chiba, Japan, 261-0004
        • Tokuyama clinic_Diabetic internal medicine
      • Hokkaido, Japan, 060-0001
        • Oodouri Diabetes, Internal medicine Clinic_Internal Medicine, Diabetes Internal Medicine
      • Tochigi, Japan, 323-0022
        • Oyama East Clinic_Internal Medicine
      • Tokyo, Japan, 103-0027
        • Tokyo-Eki Center-building Clinic_Internal Medicine
      • Tokyo, Japan, 104-0031
        • Fukuwa Clinic_Internal Medicine
      • Tokyo, Japan, 113-8431
        • Juntendo University Hospital_Diabetes, endocrinology and metabolism
    • Miyazaki
      • Miyazaki, Miyazaki, Japan, 880-0034
        • Heiwadai Hospital_Internal Medicine
  • Poland
      • Bialystok, Poland, 15-404
        • SNZOZ Lege Artis
      • Gdansk, Poland, 80-214
        • Uniwersyteckie Centrum Kliniczne Regionalne Centrum Diabetologii
      • Katowice, Poland, 40-568
        • Care Clinic Sp. z o. o.
      • Krakow, Poland, 30-033
        • Grazyna Pulka Specjalistyczny Osrodek "All-Med"
      • Lodz, Poland, 90-132
        • Gabinet Lekarski Malgorzata Saryusz-Wolska
      • Lodz, Poland, 90-338
        • Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.
      • Lublin, Poland, 20-362
        • Velocity Nova Sp. z o.o.
      • Warsaw, Poland, 00-710
        • NBR Polska Tomasz Klodawski
      • Warsaw, Poland, 02-507
        • PANSTWOWY INSTYTUT MEDYCZNY MSWiA
      • Warsaw, Poland, 02-798
        • Medical Concierge Centrum Medyczne
      • Zabrze, Poland, 41-807
        • Clinhouse Centrum Medyczne
    • Lubelski
      • Lublin, Lubelski, Poland, 20-538
        • NZOZ Przychodnia Specjalistyczna Medica
    • Podlaskie Voivodeship
      • Bialystok, Podlaskie Voivodeship, Poland, 15-435
        • NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska
    • Świętokrzyskie Voivodeship
      • Staszów, Świętokrzyskie Voivodeship, Poland, 28-200
        • Velocity Nova Sp. z o.o.
  • Puerto Rico
      • Bayamón, Puerto Rico, 00959
        • Advanced Clinical Research LLC
  • South Africa
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 1812
        • Dr R Dulabh
      • Johannesburg, Gauteng, South Africa, 2001
        • Newtown Clinical Research
      • Roodepoort, Gauteng, South Africa, 1724
        • Roodepoort Medicross Clinical Research Centre
    • KwaZulu-Natal
      • Durban, KwaZulu-Natal, South Africa, 4450
        • Dr Pillay's Rooms
      • KwaDukuza, KwaZulu-Natal, South Africa, 4449
        • Clinical Research Institute of South Africa
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7572
        • Langeberg Clinical Trials
  • Turkey (Türkiye)
      • Antalya, Turkey (Türkiye), 07058
        • Akdeniz University Tip Fakultesi Hastanesi
      • Antalya, Turkey (Türkiye), 07058
        • Akdeniz Üniversitesi Hastanesi- Endokrinoloji
      • Istanbul, Turkey (Türkiye), 34371
        • Seyrantepe Hamidiye Etfal Egitim ve Arastirma Hastanesi
      • Istanbul, Turkey (Türkiye), 34899
        • T.C. Saglik Bakanligi Pendik Egitim ve Arastirma Hastanesi
      • Istanbul, Turkey (Türkiye), 34480
        • Başakşehir Çam ve Sakura Şehir Hastanesi
      • Istanbul, Turkey (Türkiye), 34371
        • Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi- Seyrantepe Yerleşkesi- Endokrinoloji
      • Istanbul, Turkey (Türkiye), 34390
        • İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Endokrinoloji
      • Tekirdağ, Turkey (Türkiye), 59030
        • Tekirdağ Namık Kemal Üniversitesi Hastanesi- Dahiliye
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Univ of Alabama_Birmingham
    • California
      • Concord, California, United States, 94520
        • John Muir Physicians Network
      • La Jolla, California, United States, 92037
        • Scripps Whittier Diabetes Inst
      • Lancaster, California, United States, 93534
        • First Valley Med Grp Lancaster
      • Lincoln, California, United States, 95821
        • Clinical Trials Research_Sacramento
      • Palm Springs, California, United States, 92262
        • Desert Oasis Hlthcr Med Group
      • Palm Springs, California, United States, 91355
        • Desert Oasis Hlthcr Med Group
    • Florida
      • Fleming Island, Florida, United States, 32003
        • Northeast Research Institute
      • Jacksonville, Florida, United States, 32208
        • East Coast Institute for Research
      • Winter Haven, Florida, United States, 33880
        • Clinical Research of Cent FL
    • Georgia
      • Atlanta, Georgia, United States, 30318
        • Atlanta Diabetes Associates
      • Roswell, Georgia, United States, 30076
        • Endo Res Solutions Inc
    • Hawaii
      • Honolulu, Hawaii, United States, 96814
        • East West Medical Research Institute_Honolulu
    • Idaho
      • Blackfoot, Idaho, United States, 83221
        • Elite Clinical Trials
    • Illinois
      • Chicago, Illinois, United States, 60607
        • Cedar-Crosse Research Center
      • Skokie, Illinois, United States, 60077
        • Endeavor Health
    • Kansas
      • Topeka, Kansas, United States, 66606
        • Cotton-O'Neil Diab & Endo Ctr
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • The Research Group of Lexington LLC
    • Maryland
      • Rockville, Maryland, United States, 20852
        • Endo and Metab Consultants
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Methodist Phys. Clinic
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Albuquerque Clin Trials, Inc.
    • New York
      • Albany, New York, United States, 12203
        • AMC Community Endocrinology
      • West Seneca, New York, United States, 14224
        • Southgate Medical Group, LLP
    • North Carolina
      • Greensboro, North Carolina, United States, 27408
        • PharmQuest Life Sciences LLC
      • Greenville, North Carolina, United States, 27834
        • Physician's East Endocrinology
    • Ohio
      • Canton, Ohio, United States, 44718
        • Diab & Endo Assoc of Stark Co
      • Maumee, Ohio, United States, 43537
        • Advanced Medical Research
      • Wadsworth, Ohio, United States, 44281-9236
        • New Venture Medical Research
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74137
        • Essential Medical Research LLC
    • Tennessee
      • Kingsport, Tennessee, United States, 37660
        • Holston Medical Group
    • Texas
      • Amarillo, Texas, United States, 79106
        • Amarillo Med Spec LLP
      • Austin, Texas, United States, 78759
        • Velocity Clinical Research- Cedar Park
      • Dallas, Texas, United States, 75231
        • North Texas Endocrine Center
      • Dallas, Texas, United States, 75230
        • Velocity Clinical Res-Dallas
      • Fort Worth, Texas, United States, 76132
        • Diabetes and Thyroid Ctr of FW
      • Lampasas, Texas, United States, 76550
        • Fmc Science, Llc
      • Red Oak, Texas, United States, 75154
        • Epic Medical Research
      • San Antonio, Texas, United States, 78209
        • Quality Research Inc
      • San Antonio, Texas, United States, 78229
        • Flourish Research
      • Shavano Park, Texas, United States, 78231
        • Consano Clinical Research, LLC
      • Sugar Land, Texas, United States, 77478
        • Simcare Medical Research, LLC
    • Utah
      • Bountiful, Utah, United States, 84010
        • Wade Family Medicine
    • Virginia
      • Newport News, Virginia, United States, 23606
        • TPMG Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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).

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).
  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IcoSema
Participants will receive once weekly IcoSema subcutaneously with or without oral anti diabetic drugs for 40 weeks.
Drug: IcoSema
IcoSema will be administered subcutaneously.
Experimental: Insulin glargine
Participants will receive once daily insulin glargine subcutaneously with or without oral anti diabetic drugs for 40 weeks.
Drug: Insulin glargine
Insulin glargine will be administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in glycated haemoglobin (HbA1c)
Time Frame: From baseline (week 0) to week 40
Measured in percentage (%)-point.
From baseline (week 0) to week 40

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in body weight
Time Frame: From baseline (week 0) to week 40
Measured in kilogram (kg).
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])
Time Frame: From week 36 to week 40
Measured in % of readings.
From week 36 to week 40
Time spent less than (<) 3.0 mmol/L (54 mg/dL)
Time Frame: From week 36 to week 40
Measured in % of readings.
From week 36 to week 40
Time spent greater than (>) 10.0 mmol/L (180 mg/dL)
Time Frame: From week 36 to week 40
Measured in % of readings.
From week 36 to week 40
Weekly basal insulin dose
Time Frame: From week 38 to week 40
Measured in units of insulin.
From week 38 to week 40
Change in fasting plasma glucose (FPG)
Time Frame: From baseline (week 0) to week 40
Measured in mmol/l.
From baseline (week 0) to week 40
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction
Time Frame: From baseline (week 0) to week 40
The DTSQs items are scored on a 7-point graded response scale ranging from 0 to 6. Score ranges from 0 to 36. Higher scores indicate greater the satisfaction with medication.
From baseline (week 0) to week 40
Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by blood glucose meter) or severe hypoglycaemic episodes (level 3)
Time Frame: From baseline (week 0) to week 45
Measured in number of episodes.
From baseline (week 0) to week 45
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 45
Measured in number of episodes.
From baseline (week 0) to week 45
Number of severe hypoglycaemic episodes (level 3)
Time Frame: From baseline (week 0) to week 45
Measured in number of episodes.
From baseline (week 0) to week 45

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novo Nordisk A/S

Investigators

  • Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2024

Primary Completion (Actual)

May 27, 2025

Study Completion (Actual)

July 8, 2025

Study Registration Dates

First Submitted

February 13, 2024

First Submitted That Met QC Criteria

February 13, 2024

First Posted (Actual)

February 21, 2024

Study Record Updates

Last Update Posted (Actual)

June 5, 2026

Last Update Submitted That Met QC Criteria

June 4, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NN1535-4988
  • U1111-1283-8648 (Other Identifier: World Health Organization (WHO))
  • 2022-502484-38-00 (Other Identifier: European Medicines Agency (EMA))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Type 2 Diabetes

Clinical Trials on IcoSema

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Australia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe