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)
NCT ID: NCT05259033
Last Updated: 2025-07-09
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
683 participants
INTERVENTIONAL
2022-04-11
2024-01-16
Brief Summary
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The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to semaglutide.
Participants will either get IcoSema or semaglutide. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe semaglutide in many countries.
Participants will get IcoSema or semaglutide, which they must inject once a week with a pen, which has a small needle, in a skin fold in the thigh, upper arm, or stomach.
The study will last for about 1 year and 1 month. Participants will have 18 clinic visits, 34 phone/video calls with the study doctor, and 4 contacts with the site that can either be clinic visits or phone/video calls.
At 11 clinic visits participants will have blood samples taken. At 7 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit.
Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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IcoSema
Participants will get once weekly dose
IcoSema
IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen.
For about 1 year and 1 month.
Semaglutide
Participants will get once weekly dose
Semaglutide 1 mg
Semaglutide 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.
Interventions
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IcoSema
IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen.
For about 1 year and 1 month.
Semaglutide 1 mg
Semaglutide 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.
Eligibility Criteria
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Inclusion Criteria
* Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
* HbA1c of 7.0 - 10.0% (53.0 - 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.
* Insulin naïve. The following exceptions are permitted: short term insulin treatment for a maximum of 14 days before screening and/or prior insulin treatment for gestational diabetes.
* Treated with stable doses of daily or weekly GLP-1 receptor agonist (excluding once weekly semaglutide with doses higher than 1.0 mg) according to local label for the treatment of diabetes for 90 days or more before screening. The treatment can be with or without any of the following anti diabetic drugs with stable doses for 90 days or more before screening: Metformin - Sulfonylureas (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Meglitinides (glinides)(Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - DPP 4 inhibitors (Sulfonylureas, meglitinides (glinides) and DPP 4 inhibitors must be discontinued at randomisation) - Sodium glucose co transporter 2 inhibitors - Alpha-glucosidase inhibitors - Thiazolidinediones - Marketed oral combination products only including the products listed above.
* Body mass index (BMI) below or equal to 40.0 kg/m\^2.
* Any episodes (as declared by the participant or in the medical records) of diabetic ketoacidosis 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.
* 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
* 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).
18 Years
ALL
No
Sponsors
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Novo Nordisk A/S
INDUSTRY
Responsible Party
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Principal Investigators
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Clinical Transparency (dept. 1452)
Role: STUDY_DIRECTOR
Novo Nordisk A/S
Locations
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Univ of AL at Birmingham_BRM
Birmingham, Alabama, United States
Pri Med Grp dba/Gil Ctr Fam
Gilbert, Arizona, United States
Clinical Research Institute of Arizona
Sun City West, Arizona, United States
John Muir Physicians Network
Concord, California, United States
Velocity Clin Res Los Angeles
Los Angeles, California, United States
Velocity Clin Res Wstlke
Los Angeles, California, United States
Valley Clinical Trials, Inc.
Northridge, California, United States
Premier Medical Center, Inc.
Toluca Lake, California, United States
Northeast Research Institute
Fleming Island, Florida, United States
Northeast Res Inst. Inc.
Jacksonville, Florida, United States
Est Cst Inst for Rsrch,Jksnvil
Jacksonville, Florida, United States
South Broward Research LLC
Miramar, Florida, United States
Adult Medicine of Lake County, Inc.
Mt. Dora, Florida, United States
Florida Inst For Clin Res
Orlando, Florida, United States
Florida Institute For Clinical Research
Orlando, Florida, United States
Oviedo Medical Research, LLC
Oviedo, Florida, United States
Metabolic Research Institute Inc
West Palm Beach, Florida, United States
Javara/Privia Med Grp GA,LLC
Albany, Georgia, United States
East West Med Res Inst
Honolulu, Hawaii, United States
Saltzer Medical Group Research
Nampa, Idaho, United States
Endeavor Health
Skokie, Illinois, United States
Ileana J Tandron APMC
Slidell, Louisiana, United States
MedStar Hlth Res Institute
Hyattsville, Maryland, United States
Northern Pines Hlth Ctr, PC
Buckley, Michigan, United States
Palm Research Center Inc-Vegas
Las Vegas, Nevada, United States
John J Shelmet, MD
Lawrenceville, New Jersey, United States
Albuquerque Clin Trials, Inc.
Albuquerque, New Mexico, United States
Southgate Medical Group, LLP
West Seneca, New York, United States
PharmQuest Life Sciences LLC
Greensboro, North Carolina, United States
Diab & Endo Assoc of Stark Co
Canton, Ohio, United States
New Venture Medical Research
Wadsworth, Ohio, United States
Thomas Jefferson Univ Di Rsrch Ctr
Philadelphia, Pennsylvania, United States
Palmetto Clinical Research
Summerville, South Carolina, United States
AM Diabetes And Endocrinology Center
Bartlett, Tennessee, United States
Chattanooga Medical Research, LLC
Chattanooga, Tennessee, United States
Amarillo Med Spec LLP
Amarillo, Texas, United States
Texas Diab & Endo, P.A.
Austin, Texas, United States
Texas Diabetes & Endocrinology
Austin, Texas, United States
Osvaldo A. Brusco MD PA
Corpus Christi, Texas, United States
North Texas Endocrine Center
Dallas, Texas, United States
UT Southwestern Med Cntr
Dallas, Texas, United States
Diabetes and Thyroid Ctr of FW
Fort Worth, Texas, United States
DCOL Ctr for Clin Res
Longview, Texas, United States
Texas Diabetes & Endocrinology_Round Rock
Round Rock, Texas, United States
NE Clin Res of San Antonio
San Antonio, Texas, United States
Sugar Lakes Family Practice PA
Sugar Land, Texas, United States
Chrysalis Clinical Research
St. George, Utah, United States
Javara Inc. / Privia Medical Group LLC_Forest
Forest, Virginia, United States
Javara Inc/Privia Md GpLLC Fst
Forest, Virginia, United States
TPMG Clinical Research
Newport News, Virginia, United States
Centro de Diabetes Metabolismo e Endocrinologia
Fortaleza, Ceará, Brazil
Instituto de Ciências Farmacêuticas de Estudos e Pesquisas
Aparecida de Goiânia, Goiás, Brazil
Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV
Curitiba, Paraná, Brazil
Centro de Diabetes Curitiba
Curitiba, Paraná, Brazil
Instituto São José dos Campos em Pesquisas Médicas
São José dos Campos, São Paulo, Brazil
BR Trials - Ensaios Clínicos e Consultoria Ltda.
São Paulo, São Paulo, Brazil
LMC Clinical Res Thornhill
Concord, Ontario, Canada
Medical Trust Clinics, Inc.
Courtice, Ontario, Canada
Wharton Med Clin Trials
Hamilton, Ontario, Canada
Western Univ. Cnt for Studies in Fam Med
London, Ontario, Canada
Bluewater Clin Res Group,Inc
Sarnia, Ontario, Canada
LMC Endo Centres Ltd.(Bayview)
Toronto, Ontario, Canada
Recherche GCP Research
Montreal, Quebec, Canada
Recherche GCP Research
Montreal, Quebec, Canada
LMC Clin Rsrch Inc. (Montreal)
Montreal, Quebec, Canada
LMC Clin Rsrch Inc. (Montreal)
Saint-Laurent, Quebec, Canada
Recherche Clinique Sigma inc
Québec, , Canada
Anhui Provincial Hospital-Endocrinology
Hefei, Anhui, China
Peking University People's Hospital-Endocrinology
Beijing, Beijing Municipality, China
Chongqing University Three Gorges Hospital
Chongqing, Chongqing Municipality, China
Huizhou Central People's Hospital-Endocrinology
Huizhou, Guangdong, China
Changzhou No.2 People's Hospital, Yanghu Branch
Changzhou, Jiangsu, China
The Second Affiliated Hospital of Nanjing Medical University-Endocrinology
Nanjing, Jiangsu, China
Jinan Central Hospital
Ji'nan, Shandong, China
Huashan Hospital Fudan University-Endocrinology
Shanghai, Shanghai Municipality, China
Shanghai Huashan Hospital, Affiliated to Fudan University
Shanghai, Shanghai Municipality, China
Shanghai Fifth People's Hospital-Endocrinology
Shanghai, Shanghai Municipality, China
General Hospital of Tianjin Medical University-Endocrinology
Tianjin, Tianjin Municipality, China
Tianjin Medical University Chu Hsien-I Memorial Hospital-Endocrinology
Tianjin, Tianjin Municipality, China
Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume
Bois-Guillaume, , France
Les Hopitaux de Chartres-Hopital Louis Pasteur
Le Coudray, , France
Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-1
Le Creusot, , France
Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec-1
Saint-Herblain, , France
Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2
Toulouse, , France
Centre de Recherche Clinique Portes Du Sud
Vénissieux, , France
Evangelismos Hospital
Athens, , Greece
Iatriko Psychicou Private Clinic
Athens, , Greece
'G. Gennimatas' General Hospital of Athens
Athens, , Greece
Univ Gen Hospital Larisa
Larissa, , Greece
General Hospital of Thessaloniki 'G. Gennimatas
Thessaloniki, , Greece
"Ippokrateio" G.H. of Thessaloniki
Thessaloniki, , Greece
"Thermi" Private Hosital
Thessaloniki, , Greece
General Hospital of Thessaloniki "G.Papanikolaou"
Thessaloniki, , Greece
PTE-AOK II. Belgyogyaszati Klinika es Nephrologiai Centrum
Pécs, Baranya Vármegye, Hungary
Debreceni Egyetem Belgyógyászati Klinika
Debrecen, Hajdú-Bihar, Hungary
Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika D épület
Debrecen, Hajdú-Bihar, Hungary
MED-TIMA Kft.
Budapest, , Hungary
Clalit sick fund Herzeliya
Herzeliya, Israel, Israel
Linn clinic - Clalit Health Services
Haifa, , Israel
Diabetes Clinic Wolfson MC
Holon, , Israel
Diabetes Unit Hadassah Ein Karem MC
Jerusalem, , Israel
Diabetes Clinic Meir MC
Kfar Saba, , Israel
Endrocrinolgy Clinic - Sheba Medical Center
Tel Litwinsky, , Israel
Heiwadai Hospital
Miyazaki, Miyazaki, Japan
The Institute of Medical Science, Asahi Life Foundation
Chuo-ku, Tokyo, , Japan
Futata Tetsuhiro Clinic Meinohama
Fukuoka-shi, Fukuoka, , Japan
Gifu University Hospital
Gifu, , Japan
Naka Kinen Clinic
Ibaraki, , Japan
Takatsuki Red Cross Hospital
Osaka, , Japan
Shimizu Clinic Fusa
Saitama, , Japan
Soka Sugiura Internal Medicine Clinic_Internal Medicine
Saitama, , Japan
Shinden Higashi Clinic
Sendai-shi, Miyagi, , Japan
Irkutsk State Medical Academy of Postgraduate Education
Irkutsk, , Russia
National Medical Research Center of Endocrinology
Moscow, , Russia
Limited Law Company "Healthy Family" Medicine Center"
Novosibirsk, , Russia
BHI of Omsk Region "City Hospital № 3"
Omsk, , Russia
Penza Regional Clinical Hospital named after N.N. Burdenko
Penza, , Russia
Rostov State Medical University_Rostov-on-Don
Rostov-on-Don, , Russia
Polyclinic #2 in Yoshkar-Ola
Yoshkar-Ola, , Russia
DIOLI s.r.o.
Košice, , Slovakia
HUMAN-CARE s.r.o.
Košice, , Slovakia
DIADAN, s.r.o. Kosice
Košice, , Slovakia
FNsP L. Pasteura
Košice, , Slovakia
DIA - KONTROL s.r.o.
Levice, , Slovakia
MUDr. Alena Lomencikova, s.r.o
Turčianske Teplice, , Slovakia
Primary Care Trial Center, PTC ,Gothia Forum
Gothenburg, , Sweden
Enheten för Kliniska Studier (EKS), Örebro
Örebro, , Sweden
Centrum for Diabetes, Academical Specialist Centrum
Stockholm, , Sweden
Luzerner Kantonsspital
Lucerne, , Switzerland
Kantonsspital Olten
Olten, , Switzerland
Diabetes Adipositas Zentrum Zürich
Zollikerberg, , Switzerland
Chung Shan Medical University Hospital
Taichung, , Taiwan
National Cheng Kung University Hospital
Tainan City, , Taiwan
Chi Mei Medical Center
Tainan City, , Taiwan
Taipei Veterans General Hospital
Taipei, , Taiwan
Chang Gung Medical Foundation - Linkou Branch
Taoyuan District, , Taiwan
Countries
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References
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Lingvay I, Benamar M, Chen L, Fu A, Jodar E, Nishida T, Riveline JP, Yabe D, Zueger T, Rea R. Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial. Diabetologia. 2025 Apr;68(4):739-751. doi: 10.1007/s00125-024-06348-5. Epub 2025 Jan 17.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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U1111 1260 8268
Identifier Type: OTHER
Identifier Source: secondary_id
2020 005308 21
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
NN1535-4592
Identifier Type: -
Identifier Source: org_study_id
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