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)

NCT05259033 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: NN1535-4592U1111 1260 82682020 005308 21
• Study Type: interventional
• Target: 683
• Locations: 14 countries
• Sites: 136

Brief 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. 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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (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.

  Baseline (week 0), (week 52)

Secondary Outcomes (5)

• Change From Baseline in Fasting Plasma Glucose (FPG)

  Baseline (week 0), (week 52)

• Change From Baseline in Body Weight

  Baseline (week 0), (week 52)

• 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)

  Week 0 to Week 57

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

  Week 0 to Week 57

• Number of Severe Hypoglycaemic Episodes (Level 3)

  Week 0 to Week 57

Study Arms (2)

IcoSema

EXPERIMENTAL

Participants will get once weekly dose

Drug: IcoSema

Semaglutide

EXPERIMENTAL

Participants will get once weekly dose

Drug: Semaglutide 1 mg

Interventions

IcoSema DRUG

IcoSema once weekly subcutaneously (s.c., under the skin) using a needle and a pen. For about 1 year and 1 month.

IcoSema

Semaglutide 1 mg DRUG

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.

Semaglutide

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 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (136)

Univ of AL at Birmingham_BRM

Birmingham, Alabama, 35294, United States

Location

Pri Med Grp dba/Gil Ctr Fam

Gilbert, Arizona, 85296, United States

Location

Clinical Research Institute of Arizona

Sun City West, Arizona, 85375, United States

Location

John Muir Physicians Network

Concord, California, 94520, United States

Location

Velocity Clin Res Los Angeles

Los Angeles, California, 90017, United States

Location

Velocity Clin Res Wstlke

Los Angeles, California, 90057, United States

Location

Valley Clinical Trials, Inc.

Northridge, California, 91325, United States

Location

Premier Medical Center, Inc.

Toluca Lake, California, 91602, United States

Location

Northeast Research Institute

Fleming Island, Florida, 32003, United States

Location

Northeast Res Inst. Inc.

Jacksonville, Florida, 32204, United States

Location

Est Cst Inst for Rsrch,Jksnvil

Jacksonville, Florida, 32216, United States

Location

South Broward Research LLC

Miramar, Florida, 33027, United States

Location

Adult Medicine of Lake County, Inc.

Mt. Dora, Florida, 32757, United States

Location

Florida Inst For Clin Res

Orlando, Florida, 32825, United States

Location

Florida Institute For Clinical Research

Orlando, Florida, 32825, United States

Location

Oviedo Medical Research, LLC

Oviedo, Florida, 32765, United States

Location

Metabolic Research Institute Inc

West Palm Beach, Florida, 33401, United States

Location

Javara/Privia Med Grp GA,LLC

Albany, Georgia, 31707, United States

Location

East West Med Res Inst

Honolulu, Hawaii, 96814, United States

Location

Saltzer Medical Group Research

Nampa, Idaho, 83686-6011, United States

Location

Endeavor Health

Skokie, Illinois, 60077, United States

Location

Ileana J Tandron APMC

Slidell, Louisiana, 70461-4231, United States

Location

MedStar Hlth Res Institute

Hyattsville, Maryland, 20782, United States

Location

Northern Pines Hlth Ctr, PC

Buckley, Michigan, 49620, United States

Location

Palm Research Center Inc-Vegas

Las Vegas, Nevada, 89148, United States

Location

John J Shelmet, MD

Lawrenceville, New Jersey, 08648, United States

Location

Albuquerque Clin Trials, Inc.

Albuquerque, New Mexico, 87102, United States

Location

Southgate Medical Group, LLP

West Seneca, New York, 14224, United States

Location

PharmQuest Life Sciences LLC

Greensboro, North Carolina, 27408, United States

Location

Diab & Endo Assoc of Stark Co

Canton, Ohio, 44718, United States

Location

New Venture Medical Research

Wadsworth, Ohio, 44281, United States

Location

Thomas Jefferson Univ Di Rsrch Ctr

Philadelphia, Pennsylvania, 19107, United States

Location

Palmetto Clinical Research

Summerville, South Carolina, 29485, United States

Location

AM Diabetes And Endocrinology Center

Bartlett, Tennessee, 38133, United States

Location

Chattanooga Medical Research, LLC

Chattanooga, Tennessee, 37404, United States

Location

Amarillo Med Spec LLP

Amarillo, Texas, 79106, United States

Location

Texas Diab & Endo, P.A.

Austin, Texas, 78731, United States

Location

Texas Diabetes & Endocrinology

Austin, Texas, 78749, United States

Location

Osvaldo A. Brusco MD PA

Corpus Christi, Texas, 78414, United States

Location

North Texas Endocrine Center

Dallas, Texas, 75231, United States

Location

UT Southwestern Med Cntr

Dallas, Texas, 75390-9302, United States

Location

Diabetes and Thyroid Ctr of FW

Fort Worth, Texas, 76132, United States

Location

DCOL Ctr for Clin Res

Longview, Texas, 75605, United States

Location

Texas Diabetes & Endocrinology_Round Rock

Round Rock, Texas, 78681, United States

Location

NE Clin Res of San Antonio

San Antonio, Texas, 78233, United States

Location

Sugar Lakes Family Practice PA

Sugar Land, Texas, 77479, United States

Location

Chrysalis Clinical Research

St. George, Utah, 84790, United States

Location

Javara Inc. / Privia Medical Group LLC_Forest

Forest, Virginia, 24551, United States

Location

Javara Inc/Privia Md GpLLC Fst

Forest, Virginia, 24551, United States

Location

TPMG Clinical Research

Newport News, Virginia, 23606, United States

Location

Centro de Diabetes Metabolismo e Endocrinologia

Fortaleza, Ceará, 60150-162, Brazil

Location

Instituto de Ciências Farmacêuticas de Estudos e Pesquisas

Aparecida de Goiânia, Goiás, 74935-530, Brazil

Location

Quanta Diagnóstico Nuclear / Medicina Nuclear Alto da XV

Curitiba, Paraná, 80045-110, Brazil

Location

Centro de Diabetes Curitiba

Curitiba, Paraná, 80810-040, Brazil

Location

Instituto São José dos Campos em Pesquisas Médicas

São José dos Campos, São Paulo, 12243-280, Brazil

Location

BR Trials - Ensaios Clínicos e Consultoria Ltda.

São Paulo, São Paulo, 01236-030, Brazil

Location

LMC Clinical Res Thornhill

Concord, Ontario, L4K 4M2, Canada

Location

Medical Trust Clinics, Inc.

Courtice, Ontario, L1E2J5, Canada

Location

Wharton Med Clin Trials

Hamilton, Ontario, L8L 5G8, Canada

Location

Western Univ. Cnt for Studies in Fam Med

London, Ontario, N6G 2M1, Canada

Location

Bluewater Clin Res Group,Inc

Sarnia, Ontario, N7T 4X3, Canada

Location

LMC Endo Centres Ltd.(Bayview)

Toronto, Ontario, M4G 3E8, Canada

Location

Recherche GCP Research

Montreal, Quebec, H1M 1B1, Canada

Location

Recherche GCP Research

Montreal, Quebec, H1Y 3H5, Canada

Location

LMC Clin Rsrch Inc. (Montreal)

Montreal, Quebec, H4T 1Z9, Canada

Location

LMC Clin Rsrch Inc. (Montreal)

Saint-Laurent, Quebec, H4T 1Z9, Canada

Location

Recherche Clinique Sigma inc

Québec, G1G 3Y8, Canada

Location

Anhui Provincial Hospital-Endocrinology

Hefei, Anhui, 230001, China

Location

Peking University People's Hospital-Endocrinology

Beijing, Beijing Municipality, 100044, China

Location

Chongqing University Three Gorges Hospital

Chongqing, Chongqing Municipality, 404000, China

Location

Huizhou Central People's Hospital-Endocrinology

Huizhou, Guangdong, 516001, China

Location

Changzhou No.2 People's Hospital, Yanghu Branch

Changzhou, Jiangsu, 213003, China

Location

The Second Affiliated Hospital of Nanjing Medical University-Endocrinology

Nanjing, Jiangsu, 210011, China

Location

Jinan Central Hospital

Ji'nan, Shandong, 250013, China

Location

Huashan Hospital Fudan University-Endocrinology

Shanghai, Shanghai Municipality, 200040, China

Location

Shanghai Huashan Hospital, Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Shanghai Fifth People's Hospital-Endocrinology

Shanghai, Shanghai Municipality, 200240, China

Location

General Hospital of Tianjin Medical University-Endocrinology

Tianjin, Tianjin Municipality, 300052, China

Location

Tianjin Medical University Chu Hsien-I Memorial Hospital-Endocrinology

Tianjin, Tianjin Municipality, 300070, China

Location

Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume

Bois-Guillaume, 76230, France

Location

Les Hopitaux de Chartres-Hopital Louis Pasteur

Le Coudray, 28630, France

Location

Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-1

Le Creusot, 71200, France

Location

Centre Hospitalier Universitaire de Nantes-Hopital Nord Laennec-1

Saint-Herblain, 44800, France

Location

Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-2

Toulouse, 31054, France

Location

Centre de Recherche Clinique Portes Du Sud

Vénissieux, 69200, France

Location

Evangelismos Hospital

Athens, 10676, Greece

Location

Iatriko Psychicou Private Clinic

Athens, 115 25, Greece

Location

'G. Gennimatas' General Hospital of Athens

Athens, 115 27, Greece

Location

Univ Gen Hospital Larisa

Larissa, 41110, Greece

Location

General Hospital of Thessaloniki 'G. Gennimatas

Thessaloniki, 54635, Greece

Location

"Ippokrateio" G.H. of Thessaloniki

Thessaloniki, 54642, Greece

Location

"Thermi" Private Hosital

Thessaloniki, 57001, Greece

Location

General Hospital of Thessaloniki "G.Papanikolaou"

Thessaloniki, 57010, Greece

Location

PTE-AOK II. Belgyogyaszati Klinika es Nephrologiai Centrum

Pécs, Baranya Vármegye, 7623, Hungary

Location

Debreceni Egyetem Belgyógyászati Klinika

Debrecen, Hajdú-Bihar, 4032, Hungary

Location

Debreceni Egyetem Klinikai Központ Belgyógyászati Klinika D épület

Debrecen, Hajdú-Bihar, H-4043, Hungary

Location

MED-TIMA Kft.

Budapest, 1132, Hungary

Location

Clalit sick fund Herzeliya

Herzeliya, Israel, 4630945, Israel

Location

Linn clinic - Clalit Health Services

Haifa, 35152, Israel

Location

Diabetes Clinic Wolfson MC

Holon, 58100, Israel

Location

Diabetes Unit Hadassah Ein Karem MC

Jerusalem, 91120, Israel

Location

Diabetes Clinic Meir MC

Kfar Saba, 44281, Israel

Location

Endrocrinolgy Clinic - Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

Heiwadai Hospital

Miyazaki, Miyazaki, 880-0034, Japan

Location

The Institute of Medical Science, Asahi Life Foundation

Chuo-ku, Tokyo, 103-0002, Japan

Location

Futata Tetsuhiro Clinic Meinohama

Fukuoka-shi, Fukuoka, 819-0006, Japan

Location

Gifu University Hospital

Gifu, 501-1194, Japan

Location

Naka Kinen Clinic

Ibaraki, 311-0113, Japan

Location

Takatsuki Red Cross Hospital

Osaka, 569-1045, Japan

Location

Shimizu Clinic Fusa

Saitama, 336-0967, Japan

Location

Soka Sugiura Internal Medicine Clinic_Internal Medicine

Saitama, 340-0015, Japan

Location

Shinden Higashi Clinic

Sendai-shi, Miyagi, 983-0039, Japan

Location

Irkutsk State Medical Academy of Postgraduate Education

Irkutsk, 664049, Russia

Location

National Medical Research Center of Endocrinology

Moscow, 117292, Russia

Location

Limited Law Company "Healthy Family" Medicine Center"

Novosibirsk, 630099, Russia

Location

BHI of Omsk Region "City Hospital № 3"

Omsk, 644029, Russia

Location

Penza Regional Clinical Hospital named after N.N. Burdenko

Penza, 440052, Russia

Location

Rostov State Medical University_Rostov-on-Don

Rostov-on-Don, 344022, Russia

Location

Polyclinic #2 in Yoshkar-Ola

Yoshkar-Ola, 424004, Russia

Location

DIOLI s.r.o.

Košice, 040 01, Slovakia

Location

HUMAN-CARE s.r.o.

Košice, 040 01, Slovakia

Location

DIADAN, s.r.o. Kosice

Košice, 04011, Slovakia

Location

FNsP L. Pasteura

Košice, 04190, Slovakia

Location

DIA - KONTROL s.r.o.

Levice, 93401, Slovakia

Location

MUDr. Alena Lomencikova, s.r.o

Turčianske Teplice, 039 01, Slovakia

Location

Primary Care Trial Center, PTC ,Gothia Forum

Gothenburg, 413 46, Sweden

Location

Enheten för Kliniska Studier (EKS), Örebro

Örebro, 703 62, Sweden

Location

Centrum for Diabetes, Academical Specialist Centrum

Stockholm, 113 65, Sweden

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Kantonsspital Olten

Olten, 4600, Switzerland

Location

Diabetes Adipositas Zentrum Zürich

Zollikerberg, 8125, Switzerland

Location

Chung Shan Medical University Hospital

Taichung, 402, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

Chi Mei Medical Center

Tainan, 710, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang Gung Medical Foundation - Linkou Branch

Taoyuan District, 333, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 39820580 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

semaglutide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Transparency (dept. 1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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 10, 2022
• First Posted: February 28, 2022
• Study Start: April 11, 2022
• Primary Completion: December 13, 2023
• Study Completion: January 16, 2024
• Last Updated: July 9, 2025
• Results First Posted: January 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

US (50); CA (11); IL (6); RU (7); SL (6); FR (6); HU (4); JP (9); SE (3); GR (8); BR (6); CH (3); CN (12); TW (5)