AzTrials
AzTrials

Diabetes Mellitus, Type 2Phase 3COMBINE 2NCT05259033

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)

A Phase 3 study testing IcoSema and Semaglutide 1 mg in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 193 sites in 15 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to semaglutide taken once a week in people with type 2 diabetes. The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to semaglutide. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
IcoSema and Semaglutide 1 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
683 participants
Where
193 sitesin 15 countries
Study dates
11 Apr 2022to 16 Jan 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female and age above or equal to 18 years at the time of signing informed consent.
  • 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.

Who cannot join

  • Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using a 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).
  • Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening.
  • 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

Trial locations and contacts

193 sites in 15 countries.

193 sites in 15 countries

United States76 sites

  • Javara/Privia Med Grp GA,LLC

    Albany, Georgia, 31707

  • Albuquerque Clin Trials, Inc.

    Albuquerque, New Mexico, 87102

  • Amarillo Med Spec LLP

    Amarillo, Texas, 79106

  • Texas Diab & Endo, P.A.

    Austin, Texas, 78731

  • Texas Diabetes & Endocrinology

    Austin, Texas, 78749

  • AM Diabetes And Endocrinology Center

    Bartlett, Tennessee, 38133

  • Univ of AL at Birmingham_BRM

    Birmingham, Alabama, 35294

  • Wade Family Medicine

    Bountiful, Utah, 84010

  • Northern Pines Hlth Ctr, PC

    Buckley, Michigan, 49620

  • Diab & Endo Assoc of Stark Co

    Canton, Ohio, 44718

  • Chattanooga Medical Research, LLC

    Chattanooga, Tennessee, 37404

  • Cedar-Crosse Research Center

    Chicago, Illinois, 60607

  • John Muir Physicians Network

    Concord, California, 94520

  • Osvaldo A. Brusco MD

    Corpus Christi, Texas, 78414

  • Cedar Research

    Dallas, Texas, 75038

  • North Texas Endocrine Center

    Dallas, Texas, 75231

  • UT Southwestern Med Cntr

    Dallas, Texas, 75390-9302

  • Northeast Research Institute

    Fleming Island, Florida, 32003

  • Javara Inc. / Privia Medical Group LLC_Forest

    Forest, Virginia, 24551

  • Javara Inc/Privia Md GpLLC Fst

    Forest, Virginia, 24551

  • Diabetes and Thyroid Ctr of FW

    Fort Worth, Texas, 76132

  • Pri Med Grp dba/Gil Ctr Fam

    Gilbert, Arizona, 85296

  • Macoupin Research Group

    Gillespie, Illinois, 62033

  • PharmQuest Life Sciences LLC

    Greensboro, North Carolina, 27408

  • Encore Medical Research LLC

    Hollywood, Florida, 33024

  • East West Med Res Inst

    Honolulu, Hawaii, 96814

  • PrimeCare Medical Group

    Houston, Texas, 77024

  • MedStar Hlth Res Institute

    Hyattsville, Maryland, 20782

  • Northeast Res Inst. Inc.

    Jacksonville, Florida, 32204

  • Est Cst Inst for Rsrch,Jksnvil

    Jacksonville, Florida, 32216

  • Scripps Whittier Diabetes Inst

    La Jolla, California, 92037

  • Palm Research Center Inc-Vegas

    Las Vegas, Nevada, 89148

  • John J Shelmet, MD

    Lawrenceville, New Jersey, 08648

  • Clinical Trials Research_Sacramento

    Lincoln, California, 95821

  • DCOL Ctr for Clin Res

    Longview, Texas, 75605

  • Downtown LA Res Ctr. Inc.

    Los Angeles, California, 90017

  • Velocity Clin Res Los Angeles

    Los Angeles, California, 90017

  • Velocity Clin Res Wstlke

    Los Angeles, California, 90057

  • L-MARC Research Center

    Louisville, Kentucky, 40213

  • ActivMed Practice & Research LLC

    Methuen, Massachusetts, 01844

  • University Of Miami

    Miami, Florida, 33136

  • South Broward Research LLC

    Miramar, Florida, 33027

  • Adult Medicine of Lake County, Inc.

    Mt. Dora, Florida, 32757

  • Saltzer Medical Group Research

    Nampa, Idaho, 83686-6011

  • Southern New Hampshire Diabete

    Nashua, New Hampshire, 03060

  • TPMG Clinical Research

    Newport News, Virginia, 23606

  • Valley Clinical Trials, Inc.

    Northridge, California, 91325

  • Univ of Nebraska Medical CTR

    Omaha, Nebraska, 68198-3020

  • Clinical Neuroscience Solution

    Orlando, Florida, 32801

  • Florida Institute For Clinical Research

    Orlando, Florida, 32825

  • Oviedo Medical Research, LLC

    Oviedo, Florida, 32765

  • Four Rivers Clinical Research Inc

    Paducah, Kentucky, 42001

  • Thomas Jefferson Univ Di Rsrch Ctr

    Philadelphia, Pennsylvania, 19107

  • Phoenician Centers for Research & Innovation PCRI

    Phoenix, Arizona, 85021

  • Endo Res Solutions Inc

    Roswell, Georgia, 30076

  • Texas Diabetes & Endocrinology_Round Rock

    Round Rock, Texas, 78681

  • NE Clin Res of San Antonio

    San Antonio, Texas, 78233

  • San Diego Family Care_San Diego

    San Diego, California, 92111

  • Hillcrest Clinical Research

    Simpsonville, South Carolina, 29681-1538

  • Endeavor Health

    Skokie, Illinois, 60077

  • Ileana J Tandron APMC

    Slidell, Louisiana, 70461-4231

  • Endocrine Associates of Long Island, PC

    Smithtown, New York, 11787

  • Central Illinois Diabetes and Clinical Research

    Springfield, Illinois, 62711

  • Chrysalis Clinical Research

    St. George, Utah, 84790

  • Sugar Lakes Family Practice PA

    Sugar Land, Texas, 77479

  • Palmetto Clinical Research

    Summerville, South Carolina, 29485

  • Clinical Research Institute of Arizona

    Sun City West, Arizona, 85375

  • Premier Medical Center, Inc.

    Toluca Lake, California, 91602

  • Cotton-O'Neil Diab & Endo Ctr

    Topeka, Kansas, 66606

  • Velocity Clin. Res Valparaiso

    Valparaiso, Indiana, 46383

  • Hillcrest Family Health Center

    Waco, Texas, 76710

  • New Venture Medical Research

    Wadsworth, Ohio, 44281

  • Iowa Diab & Endo Res Center

    West Des Moines, Iowa, 50266

  • Metabolic Research Institute Inc

    West Palm Beach, Florida, 33401

  • Southgate Medical Group, LLP

    West Seneca, New York, 14224

  • Accellacare

    Wilmington, North Carolina, 28401

Other trials in United States

Canada24 sites

  • ViaCar Recherche Clinique Inc

    Brossard, Quebec, J4Z 2K9

  • Dawson Clinical Research

    Cambridge, Ontario, N1H 1B1

  • LMC Clinical Res Thornhill

    Concord, Ontario, L4K 4M2

  • Medical Trust Clinics, Inc.

    Courtice, Ontario, L1E2J5

  • Wharton Medical Clinic Clinical Trials (Hamilton)

    Hamilton, Ontario, L8L 5G8

  • Premier Clinical Trial Research Network (PCTRN)

    Hamilton, Ontario, L8M 1K7

  • Western Univ. Cnt for Studies in Fam Med

    London, Ontario, N6G 2M1

  • G.A. Research Associates Ltd.

    Moncton, New Brunswick, E1G 1A7

  • Recherche GCP Research

    Montreal, Quebec, H1M 1B1

  • Recherche GCP Research

    Montreal, Quebec, H1Y 3H5

  • Recherche GCP Research_Montreal

    Montreal, Quebec, H2R 1V6

  • Centre Medical Acadie

    Montreal, Quebec, H4N 2W2

  • LMC Clin Rsrch Inc. (Montreal)

    Montreal, Quebec, H4T 1Z9

  • Commonwealth Medical Clinic

    Mount Pearl, Newfoundland and Labrador, A1N 1W7

  • Recherche Clinique Sigma inc

    Québec, G1G 5X1

  • Diex Recherche Quebec

    Québec, G1V 4T3

  • LMC Clin Rsrch Inc. (Montreal)

    Saint-Laurent, Quebec, H4T 1Z9

  • Ctr Méd. et pro d l'Ost d port

    Saint-Marc-des-Carrieres, Quebec, G0A 4B0

  • Bluewater Clin Res Group,Inc

    Sarnia, Ontario, N7T 4X3

  • LMC Endo Centres Ltd.(Bayview)

    Toronto, Ontario, M4G 3E8

  • BC Diabetes Canada

    Vancouver, British Columbia, V5Y 3W2

  • St Pauls Hospital

    Vancouver

  • Rivergrove Medical Clinic

    Winnipeg, Manitoba, R2V 4W3

  • Winnipeg Clinic

    Winnipeg, Manitoba, R3C 0N2

Other trials in Canada

China12 sites

  • Peking University People's Hospital-Endocrinology

    Beijing, Beijing Municipality, 100044

  • Changzhou No.2 People's Hospital, Yanghu Branch

    Changzhou, Jiangsu, 213003

  • Chongqing University Three Gorges Hospital

    Chongqing, Chongqing Municipality, 404000

  • Anhui Provincial Hospital-Endocrinology

    Hefei, Anhui, 230001

  • Huizhou Central People's Hospital-Endocrinology

    Huizhou, Guangdong, 516001

  • Jinan Central Hospital

    Jinan, Shandong, 250013

  • The Second Affiliated Hospital of Nanjing Medical University-Endocrinology

    Nanjing, Jiangsu, 210011

  • Huashan Hospital Fudan University-Endocrinology

    Shanghai, Shanghai Municipality, 200040

  • Shanghai Huashan Hospital, Affiliated to Fudan University

    Shanghai, Shanghai Municipality, 200040

  • Shanghai Fifth People's Hospital-Endocrinology

    Shanghai, Shanghai Municipality, 200240

  • Tianjin Medical University General Hospital-Endocrinology

    Tianjin, Tianjin Municipality, 300052

  • Tianjin Medical University Chu Hsien-I Memorial Hospital-Endocrinology

    Tianjin, Tianjin Municipality, 300070

Other trials in China

Japan11 sites

  • The Institute of Medical Science, Asahi Life Foundation_Internal Medicine

    Chuo-ku, Tokyo, 103-0002

  • Futata Tetsuhiro Clinic Meinohama_Internal medicine

    Fukuoka-shi, Fukuoka, 819-0006

  • Futata Tetsuhiro Clinic Meinohama

    Fukuoka-shi, Fukuoka, 819-0006

  • Gifu University Hospital_The Third Dept. of Internal Medicine

    Gifu, 501-1194

  • Naka Kinen Clinic_Internal medicine

    Ibaraki, 311-0113

  • Heiwadai Hospital_Internal Medicine

    Miyazaki, Miyazaki, 880-0034

  • Takatsuki Red Cross Hospital_Diabetes and Endocrine Div.

    Osaka, 569-1045

  • Shimizu Clinic Fusa

    Saitama, 336-0967

  • Soka Sugiura Internal Medicine Clinic_Internal Medicine

    Saitama, 340-0015

  • Yuri Ono Clinic

    Sapporo-shi, Hokkaido, 060-0001

  • Shinden Higashi Clinic_Internal medicine

    Sendai-shi, Miyagi, 983-0039

Other trials in Japan

France10 sites

  • Centre Hospitalier Universitaire de Besancon-Hopital Jean Minjoz

    Besançon, 25030

  • Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume

    Bois-Guillaume, 76230

  • Les Hopitaux de Chartres-Hopital Louis Pasteur

    Le Coudray, 28630

  • Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu

    Le Creusot, 71200

  • Centre Medico Chirurgical Ambroise Pare Hartmann

    Neuilly-sur-Seine, 92200

  • Aphp-Hopital Lariboisiere

    Paris, 75010

  • Hospices Civils de Lyon-Hopital Lyon Sud-2

    Pierre-Bénite, 69495

  • Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec

    Saint-Herblain, 44800

  • Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2

    Toulouse, 31054

  • Centre de Recherche Clinique Portes Du Sud

    Vénissieux, 69200

Other trials in France

Greece9 sites

  • Evangelismos Hospital

    Athens, 10676

  • Iatriko Psychicou Private Clinic

    Athens, 115 25

  • 'G. Gennimatas' General Hospital of Athens

    Athens, 115 27

  • General Hospital Of Athens Korgialenio Benakio H.R.C. - Department of Endocrinology

    Athens, GR-11526

  • Univ Gen Hospital Larisa

    Larissa, 41110

  • General Hospital of Thessaloniki 'G. Gennimatas

    Thessaloniki, 54635

  • "Ippokrateio" G.H. of Thessaloniki

    Thessaloniki, 54642

  • "Thermi" Private Hosital

    Thessaloniki, 57001

  • General Hospital of Thessaloniki "G.Papanikolaou"

    Thessaloniki, 57010

Other trials in Greece

Slovakia8 sites

  • DIOLI s.r.o.

    Košice, 040 01

  • HUMAN-CARE, s.r.o.

    Košice, 040 01

  • DIADAN, s.r.o. Kosice

    Košice, 04011

  • FNsP L. Pasteura

    Košice, 04190

  • DIA - KONTROL s.r.o.

    Levice, 93401

  • Diabetologicka ambulancia SchronerMED, s.r.o.

    Moldava nad Bodvou, 045 01

  • DIABETOL, s.r.o.

    Prešov, 080 01

  • MUDr. Alena Lomencikova, s.r.o

    Turčianske Teplice, 039 01

Other trials in Slovakia

Brazil7 sites

  • Instituto de Ciências Farmacêuticas de Estudos e Pesquisas

    Aparecida de Goiânia, Goiás, 74935-530

  • Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV

    Curitiba, Paraná, 80045-110

  • Centro de Diabetes Curitiba

    Curitiba, Paraná, 80810-040

  • Centro de Estudos Em Diabetes E Hipertensão

    Fortaleza, Ceará, 60115-282

  • Centro de Diabetes Metabolismo e Endocrinologia

    Fortaleza, Ceará, 60150-162

  • Instituto São José dos Campos em Pesquisas Médicas

    São José dos Campos, São Paulo, 12243-280

  • BR Trials - Ensaios Clínicos e Consultoria Ltda.

    São Paulo, São Paulo, 01236-030

Other trials in Brazil

Russia7 sites

  • Irkutsk State Medical Academy of Postgraduate Education

    Irkutsk, 664049

  • FSBI 'I.I. Dedov National Medical Research Center of Endocrinology' of the MH of Russia

    Moscow, 117292

  • Limited Law Company "Healthy Family" Medicine Center"

    Novosibirsk, 630099

  • BHI of Omsk Region "City Hospital № 3"

    Omsk, 644029

  • Penza Regional Clinical Hospital named after N.N. Burdenko

    Penza, 440052

  • Rostov State Medical University_Rostov-on-Don

    Rostov-on-Don, 344022

  • Polyclinic #2 in Yoshkar-Ola

    Yoshkar-Ola, 424004

Other trials in Russia

Israel6 sites

  • Linn clinic - Diabetes Unit

    Haifa, 35152

  • Clalit sick fund Herzeliya

    Herzeliya, Israel, 4630945

  • Wolfson MC - Diabetes Clinic

    Holon, 58100

  • Hadassah Ein Karam MC - Diabetes Unit

    Jerusalem, 91120

  • Diabetes Clinic Meir MC

    Kfar Saba, 44281

  • Sheba MC - Endocrinology Clinic

    Tel HaShomer, 52621

Other trials in Israel

Hungary5 sites

  • Békés Megyei Központi Kórház - dr. Réthy Pál Tagkórház

    Békéscsaba, 5600

  • MED-TIMA Kft.

    Budapest, 1132

  • Debreceni Egyetem Belgyógyászati Klinika

    Debrecen, Hajdú-Bihar, 4032

  • Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika D épület

    Debrecen, Hajdú-Bihar, H-4043

  • PTE-AOK II. Belgyogyaszati Klinika es Nephrologiai Centrum

    Pécs, Baranya Vármegye, 7623

Other trials in Hungary

Switzerland5 sites

  • Luzerner Kantonsspital

    Lucerne, 6004

  • Kantonsspital Olten

    Olten, 4600

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

  • Diabetes Adipositas Zentrum Zürich

    Zollikerberg, 8125

  • Kinderspital Endokrinologie, Zürich

    Zurich

Other trials in Switzerland

Taiwan5 sites

  • Chung Shan Medical University Hospital

    Taichung, 402

  • National Cheng Kung University Hospital

    Tainan, 704

  • Chi Mei Medical Center

    Tainan, 710

  • Taipei Veterans General Hospital

    Taipei, 112

  • Chang Gung Medical Foundation - Linkou Branch

    Taoyuan, 333

Other trials in Taiwan

Sweden4 sites

  • Primary Care Trial Center, PTC ,Gothia Forum

    Gothenburg, 413 46

  • Enheten för Kliniska Studier (EKS), Örebro

    Örebro, 701 85

  • Enheten för Kliniska Studier (EKS), Örebro

    Örebro, 703 62

  • Centrum for Diabetes, Academical Specialist Centrum

    Stockholm, 113 65

Other trials in Sweden

Ukraine4 sites

  • "University Clinic" of Dnipro State Medical University - Endocrinology department

    Dnipro, 49038

  • Centre of Innovative Medical Technologies of NASU - Therapeutic and Endocrinology Department

    Kyiv, 04053

  • Komisarenko Institute of Endocrinology and Metabolism of NAMSU - Department of paediatric endocrine pathology

    Kyiv, 04114

  • Vinnytsia Regional Clinical Endocrinological Centre - Therapeutic department #2

    Vinnytsia, 21010

Other trials in Ukraine

About this study

Official title: A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Once Weekly Semaglutide, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With a GLP 1 Receptor Agonist. COMBINE 2

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to semaglutide taken once a week in people with type 2 diabetes.

The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to semaglutide.

Read more

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.

Being tested
IcoSema, Semaglutide 1 mg
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IcoSemaDrug

    IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen.

    For about 1 year and 1 month.

  • Semaglutide 1 mgDrug

    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.

Study groups in NCT05259033
Study groupRoleWhat they receive
IcoSemaExperimentalParticipants will get once weekly dose
Receives: Drug: IcoSema
SemaglutideExperimentalParticipants will get once weekly dose
Receives: Drug: Semaglutide 1 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Glycosylated Haemoglobin (HbA1c)

    Change from baseline (week 0) to week 52 in HbA1c is presented.The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above.

    Measured: Baseline (week 0), (week 52)

Secondary outcomes (5)

  1. Change From Baseline in Fasting Plasma Glucose (FPG)

    Change from baseline (week 0) to week 52 in FPG is presented.The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above.

    Measured: Baseline (week 0), (week 52)

  2. Change From Baseline in Body Weight

    Change from baseline (week 0) to week 52 in body weight is presented. The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct participant-site contact; 2) participants who withdrew their informed consent; 3) last participant-investigator contact as defined by the investigator for participants who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of participants who died before any of the above.

    Measured: Baseline (week 0), (week 52)

  3. Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) , Confirmed by Blood Glucose [BG] Meter) or Severe Hypoglycaemic Episodes (Level 3)

    Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was less than (<) 3.0 mmol/L (54 mg/dL) and level 3 had no specific glucose threshold. The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.

    Measured: Week 0 to Week 57

  4. Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter)

    Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was < 3.0 mmol/L (54 mg/dL). The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.

    Measured: Week 0 to Week 57

  5. Number of Severe Hypoglycaemic Episodes (Level 3)

    Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 3 had no specific glucose threshold.The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets.

    Measured: Week 0 to Week 57

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2022
  2. Study start11 Apr 2022
  3. Primary completion13 Dec 2023
  4. Study completion16 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
683 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05259033
Sponsor's protocol ID
NN1535-4592
Other IDs
U1111 1260 8268, 2020 005308 21
Acronym
COMBINE 2
Status last verified
May 2026
First submitted
10 Feb 2022
Last updated
12 Jun 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: "According to the Novo Nordisk disclosure commitment on novonordisk-trials.com"

Publications

  • Ji L, Andersen JD, Benamar M, Ponzani P, Unnikrishnan AG, Vinther S, Rea R. Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials. Diabetes Obes Metab. 2026 Aug 5. doi: 10.1111/dom.70895. Online ahead of print.

    PubMed 42557064

  • 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.

    PubMed 39820580

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing IcoSema and Semaglutide 1 mg in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 193 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 193 sites in United States, Canada, China, Japan, France and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Glycosylated Haemoglobin (HbA1c) (time frame: Baseline (week 0), (week 52)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05259033, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.

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