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 Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)

A 52 Week Study Comparing the Efficacy and Safety of Once Weekly IcoSema and Daily Insulin Glargine 100 Units/mL Combined With Insulin Aspart, Both Treatment Arms With or Without Oral Anti Diabetic Drugs, in Participants With Type 2 Diabetes Inadequately Controlled With Daily Basal Insulin. COMBINE 3

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin glargine taken daily with insulin aspart 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 insulin glargine taken with insulin aspart. Participants will either get IcoSema or insulin glargine taken with insulin aspart. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine and insulin aspart in many countries.

Participants will get IcoSema or insulin glargine together with insulin aspart. Participants must inject IcoSema once a week or inject insulin glargine once daily and insulin aspart 2-4 times a day. Participants will inject the medicines 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 be asked to wear a sensor that measures participants blood sugar level all the time during an 8 week period at the beginning of the study and a 4 week period at the end of the study.

Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: IcoSema; Drug: Insulin glargine; Drug: insulin aspart

• Study Type: Interventional
• Enrollment (Actual): 679
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 602 00
    • Fakultni nemocnice u sv. Anny v Brne
  • Brno, Czechia, 656 91
    • University Hospital U sv. Anny
  • Brno, Czechia, 602 00
    • Ambulance Brno s.r.o.
  • Hodonín, Czechia, 695 01
    • Dum zdravi
  • Hradec Králové, Czechia, 500 05
    • FN Hradec Králové
  • Mladá Boleslav, Czechia, 29301
    • Klinika Dr. Pírka s.r.o.
  • Prague, Czechia, 160 00
    • Fledip s.r.o.
  • Prague, Czechia, 110 00
    • Diabet2 s.r.o.
  • Prague, Czechia, 14021
    • Institut klinicke a experimentalni mediciny_Praha
  • Prague, Czechia, 18100
    • ResTrial s.r.o.
  • Prague, Czechia, 110 00
    • Diabetologická a interní ambulance Diabet2
  • Prague, Czechia, 12000
    • III. interni klinika VFN a 1. LK UK v Praze
  • Czech Republic
    • Pilsen, Czech Republic, Czechia, 304 60
      • Fakultni nemocnice Plzen
    • Pilsen, Czech Republic, Czechia, 323 00
      • Fakultni nemocnice Plzen
• France
  • La Roche-sur-Yon, France, 85295
    • Centre Hospitalier Departemental Vendee- La Roche Sur Yon
  • Le Coudray, France, 28630
    • Les Hopitaux de Chartres-Hopital Louis Pasteur
  • Le Creusot, France, 71200
    • Groupe Sos Sante-Hopital Le Creusot-Hotel Dieu-2
  • Narbonne, France, 11108
    • Centre Hospitalier de Narbonne
  • Paris, France, 75010
    • Aphp-Hopital Lariboisiere-1
  • Pessac, France, 33600
    • Centre Hospitalier Universitaire de Bordeaux-Hopital Haut Leveque-2
  • Vénissieux, France, 69200
    • Centre de Recherche Clinique Portes Du Sud
• Germany
  • Essen, Germany, 45136
    • InnoDiab Forschung GmbH
  • Essen, Germany, 45359
    • Plassmann
  • Hamburg, Germany, 22607
    • Wendisch/Dahl Hamburg (DZHW)
  • Lübeck, Germany, 23538
    • Uniklinik Schleswig-Holstein - Medizinischen Klinik I am Campus Lübeck
  • Münster, Germany, 48145
    • Institut für Diabetesforschung GmbH Münster - Dr. med. Rose
  • Oldenburg in Holstein, Germany, 23758
    • RED-Institut für medizinische Forschung und Fortbildung GmbH
  • Saint Ingbert-Oberwürzbach, Germany, 66386
    • Zentrum für klinische Studien Alexander Segner
• Hungary
  • Budapest, Hungary, 1042
    • Szőcs Depot Egészségügyi Szolgáltató Kft.
  • Budapest, Hungary, 1089
    • ClinDiab Egészségügyi Szolgáltató és Kereskedelmi Kft.
  • Budapest, Hungary, 1088
    • Semmelweis Egyetem II. Belgyógyászati Klinika
  • Budapest, Hungary, 1036
    • Clinexpert Egészségügyi Szolgáltató és Kereskedelmi Kft.
  • Békéscsaba, Hungary, 5600
    • Békés Megyei Központi Kórház - dr. Réthy Pál Tagkórház
  • Pécs, Hungary, 7623
    • Coromed SMO Kft.
• India
  • Ahmedabad, India, 390013
    • Swasthya Diabetes Care
  • Gujarat
    • Ahmedabad, Gujarat, India, 382428
      • Apollo Hospital, Ahmedabad
    • Ahmedabad, Gujarat, India, 390013
      • Swasthya Diabetes Care
    • Gandhinagar, Gujarat, India, 382428
      • Apollo Hospital International Ltd
  • Karnataka
    • Bangalore, Karnataka, India, 560010
      • Diacon Hospital Private Limited
  • Kerala
    • Trivandrum, Kerala, India, 695 607
      • Sree Gokulam Medical College & Research Foundation
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452010
      • TOTALL Diabetes Hormone Institute
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Speciality Hospital
    • Pune, Maharashtra, India, 411004
      • Sahyadri Speciality Hospital
    • Pune, Maharashtra, India, 411021
      • chelleram Diabetes Institute
  • Punjab
    • Chandigarh, Punjab, India, 160012
      • Post Graduate Institute of Medical Education & Research
    • Ludhiana, Punjab, India, 141008
      • Christian Medical College and Hospital
    • Mohali, Punjab, India, 160062
      • Fortis Heart Institute and Multispeciality Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India, 302006
      • Diabetes, Thyroid and Endocrine Centre
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Madras Diabetes Research Foundation
    • Vellore, Tamil Nadu, India, 632004
      • Christian Medical College Hospital, Vellore
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Nizams Institute of Medical Science
    • Hyderabad, Telangana, India, 500082
      • Yashoda Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226030
      • Medanta Lucknow Hospital
• Italy
  • Cittadella, Italy, 35013
    • Presidio Ospedale di Cittadella Azienda ULSS 6 Euganea
  • Milan, Italy, 20157
    • Azienda Ospedaliera Luigi Sacco
  • Partinico, Italy, 90047
    • Ospedale Civico Partinico di Palermo
  • Sesto San Giovanni (MI), Italy, 20099
    • IRCCS MultiMedica
  • Vicenza, Italy, 36061
    • Ospedale San Bassiano
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Azienda Ospedaliero-Universitaria Renato Dulbecco
  • RM
    • Roma, RM, Italy, 00128
      • Pol. Uni. Campus Biomedico
• Japan
  • Aichi, Japan, 468-0009
    • TOSAKI Clinic for Diabetes and Endocrinology_Diabetes and Endocrinology
  • Chiba-shi, Chiba, Japan, 260-0804
    • Akaicho Clinic
  • Chuo-ku, Tokyo, Japan, 103-0002
    • The Institute of Medical Science, Asahi Life Foundation
  • Chuo-ku, Tokyo, Japan, 103-0002
    • The Institute of Medical Science, Asahi Life Foundation_Internal Medicine
  • Ibaraki, Japan, 311-0113
    • Naka Kinen Clinic_Internal medicine
  • Mito-shi, Ibaraki, Japan, 311-4153
    • Minami Akatsuka Clinic
  • Osaka, Japan, 569-1045
    • Takatsuki Red Cross Hospital_Diabetes and Endocrine Div.
  • Tokyo, Japan, 104-0031
    • Fukuwa Clinic
  • Tokyo, Japan, 103-0027
    • Tokyo-Eki Center-building Clinic_Internal Medicine
  • Tokyo, Japan, 104-0031
    • Fukuwa Clinic_Internal Medicine
  • Miyazaki
    • Miyazaki, Miyazaki, Japan, 880-0034
      • Heiwadai Hospital_Internal Medicine
  • Saitama, Japan
    • Kawagoe-shi, Saitama, Japan, Japan, 350-0851
      • Asano Clinic
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 1600023
      • Tokyo Medical Univ. Hospital_Diabetes, Metabolism and Endocrinology
• Malaysia
  • Alor Star, Malaysia, 05400
    • Klinik Kesihatan Simpang Kuala
  • Miri, Sarawak, Malaysia, 98000
    • Miri Hospital
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 16150
      • Hospital Universiti Sains Malaysia_Kota Bharu, Kelantan
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • Hospital Universiti Kebangsaan Malaysia
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • Hospital Canselor Tuanku Muhriz UKM
    • Kuala Lumpur, Kuala Lumpur, Malaysia, 59100
      • University Malaya Medical Centre
    • Lembah Pantai, Kuala Lumpur, Malaysia, 59100
      • University Malaya Medical Centre
  • Perak
    • Seri Manjung, Perak, Malaysia, 32040
      • Hospital Seri Manjung
  • Selangor
    • Ampang, Selangor, Malaysia, 68000
      • Hospital Ampang
    • Sungai Buloh, Selangor, Malaysia, 47000
      • University Technology MARA (UiTM) - Puncak Alam
    • Sungai Buloh, Selangor, Malaysia, 47000
      • University Technology MARA (UiTM) - Sg Buloh
• Poland
  • Bialystok, Poland, 15-404
    • SNZOZ Lege Artis
  • Katowice, Poland, 40-081
    • Centrum Medyczne Pratia Katowice
  • Lodz, Poland, 90-132
    • Gabinet Lekarski Malgorzata Saryusz-Wolska
  • Lodz, Poland, 90-338
    • Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.
  • Warsaw, Poland, 00-710
    • NBR Polska Tomasz Klodawski
  • Warsaw, Poland, 02-507
    • PANSTWOWY INSTYTUT MEDYCZNY MSWiA
  • Podlaskie Voivodeship
    • Bialystok, Podlaskie Voivodeship, Poland, 15-879
      • NZOZ Vita-Diabetica Malgorzata Buraczyk
    • Bialystok, Podlaskie Voivodeship, Poland, 15-435
      • NZOZ Specjalistyczny Osrodek Internistyczno-Diabetologiczny Małgorzata Arciszewska
  • Pomeranian Voivodeship
    • Gdynia, Pomeranian Voivodeship, Poland, 81-338
      • Centrum Medyczne Pratia Gdynia
• Slovenia
  • Koper, Slovenia, SI-6000
    • Healthcare Centre Koper
  • Kočevje, Slovenia, 1330
    • Healthcare centre Kocevje
  • Ljubljana, Slovenia, SI-1000
    • UKC Ljubljana, Endocrinology and Diabetes
  • Murska Sobota, Slovenia, SI-9000
    • General Hospital Murska Sobota
  • Nova Gorica, Slovenia, SI-5290
    • General Hospital Nova Gorica_Diabetes
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Medi-Clinic Bloemfontein
  • Gauteng
    • Lenasia, Gauteng, South Africa, 1827
      • Lenasia Clinical Trial Centre
    • Pretoria, Gauteng, South Africa, 0181
      • Prof P. Joshi
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7441
      • Spoke Research Inc
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital_Endocrinology
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital_Diabetes and Endocrinology
  • Bangkok, Thailand, 10700
    • Siriraj Hospital_Dept Endocrinology
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital_Endocrilogy
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital
  • Nakhon Ratchasima, Thailand, 30000
    • Maharat Nakhon Ratchasima Hospital
  • Mueang Chiang Mai District
    • Chiang Mai, Mueang Chiang Mai District, Thailand, 50200
      • Maharaj Nakorn Chiang Mai Hospital_Endocrilogy
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01250
    • Başkent Üniversitesi Adana Dr. Turgut Noyan Uygulama ve Araştırma Merkezi
  • Ankara, Turkey (Türkiye), 06010
    • Gulhane Egitim Arastirma Hastanesi
  • Antalya, Turkey (Türkiye), 07058
    • Akdeniz Üniversitesi Hastanesi- Endokrinoloji
  • Aydin, Turkey (Türkiye), 09010
    • Aydın Adnan Menderes Universitesi Hastanesi
  • Denizli, Turkey (Türkiye), 20070
    • Pamukkale Universitesi Tip Fakultesi
  • Istanbul, Turkey (Türkiye), 34400
    • Prof. Dr. Cemil Taşcıoğlu Şehir Hastanesi- Endokrinoloji
  • Izmir, Turkey (Türkiye), 35340
    • Dokuz Eylül Üniversitesi Araştırma Uygulama Hastanesi-Endokrinoloji
• United States
  • Alabama
    • Guntersville, Alabama, United States, 35976
      • Lakeview Clinical Research, LLC
  • California
    • Fresno, California, United States, 93720
      • Valley Research
    • La Jolla, California, United States, 92037
      • Scripps Wht Diab Inst La Jolla
    • Lomita, California, United States, 90717
      • Torrance Clin Res Inst, Inc.
    • Los Angeles, California, United States, 90017
      • Downtown LA Res Ctr. Inc.
    • San Diego, California, United States, 92111
      • San Diego Family Care
    • San Ramon, California, United States, 94583
      • NorCal Endocrinology and Internal Medicine
  • Colorado
    • Denver, Colorado, United States, 80209
      • Creekside Endocrine Associates
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Res Of W Florida Inc
    • Fleming Island, Florida, United States, 32003
      • Northeast Research Institute
    • Hialeah, Florida, United States, 33016
      • Sweet Hope Research Specialty
    • Jacksonville, Florida, United States, 32216
      • East Coast Institute for Research, LLC
    • Jacksonville, Florida, United States, 32204
      • Northeast Res Inst. Inc.
    • Jacksonville, Florida, United States, 32204
      • E Coast Inst for Rsrch LLC_Jacksonville
    • Miramar, Florida, United States, 33027
      • South Broward Research LLC
    • Mt. Dora, Florida, United States, 32757
      • Adult Medicine of Lake County, Inc.
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32825
      • Florida Inst For Clin Res
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute Inc
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Physicians Research Assoc. LLC
    • Roswell, Georgia, United States, 30076
      • Endo Res Solutions Inc
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Med Res Inst
  • Idaho
    • Nampa, Idaho, United States, 83686-6011
      • Saltzer Medical Group Research
  • Illinois
    • Skokie, Illinois, United States, 60077
      • Endeavor Health
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Iowa Diab & Endo Res Center
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Diab & Endo Ctr
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • The Research Group of Lexington LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • New Orleans Center for Clinical Research
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • MedStar Hlth Res Institute
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practice & Research LLC
  • Michigan
    • Buckley, Michigan, United States, 49620
      • Northern Pines Hlth Ctr, PC
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68198-3020
      • Univ of Nebraska Medical CTR
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Research Center Inc-Vegas
  • New Hampshire
    • Nashua, New Hampshire, United States, 03060
      • Southern NH Diabetes and Endocrinology
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • John J Shelmet, MD
  • New York
    • New Windsor, New York, United States, 12553
      • Mid Hudson Med Res-New Windsor
    • North Massapequa, New York, United States, 11758-1802
      • DiGiovanna Institute for Medical Education & Research
    • West Seneca, New York, United States, 14224
      • Southgate Medical Group, LLP
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Physicians East Endocrinology
    • Statesville, North Carolina, United States, 28625
      • Piedmont Healthcare/Research
    • Wilmington, North Carolina, United States, 28401
      • Accellacare
  • Ohio
    • Canton, Ohio, United States, 44718
      • Diab & Endo Assoc of Stark Co
    • Columbus, Ohio, United States, 43213
      • Central Ohio Clinical Research LLC
    • Franklin, Ohio, United States, 45005
      • Prestige Clinical Research
    • Wadsworth, Ohio, United States, 44281
      • New Venture Medical Research
  • South Carolina
    • Simpsonville, South Carolina, United States, 29681-1538
      • Hillcrest Clinical Research
  • Tennessee
    • Bartlett, Tennessee, United States, 38133
      • AM Diabetes And Endocrinology Center
    • Chattanooga, Tennessee, United States, 37411
      • Univ Diab & Endo Consultants
    • Morristown, Tennessee, United States, 37813
      • HealthStar Physicians PC
  • Texas
    • Amarillo, Texas, United States, 79106
      • Amarillo Med Spec LLP
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Res-Dallas
    • Houston, Texas, United States, 77024
      • PrimeCare Medical Group
    • Houston, Texas, United States, 77079
      • PlanIt Research, PLLC
    • Hurst, Texas, United States, 76054
      • Protenium Clinical Research
    • Laredo, Texas, United States, 78041
      • Andres Garcia-Zuniga, MD, P.A
    • Longview, Texas, United States, 75605
      • DCOL Ctr for Clin Res
    • Plano, Texas, United States, 75075
      • Clinical Investigations Of Texas
    • San Antonio, Texas, United States, 78224
      • Briggs Clinical Research, LLC
    • San Antonio, Texas, United States, 78233
      • NE Clin Res of San Antonio
    • Sugar Land, Texas, United States, 77478
      • Simcare Medical Research, LLC
  • Utah
    • St. George, Utah, United States, 84790
      • Chrysalis Clinical Research
  • Virginia
    • Winchester, Virginia, United States, 22601
      • Amherst Family Practice P.C.
  • Washington
    • Port Orchard, Washington, United States, 98366
      • Sound Medical Research
    • Renton, Washington, United States, 98057
      • Rainier Clin Res Ctr Inc
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53211
      • Ascension Medical Group- Germantown Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (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 informed consent.
• Diagnosed with type 2 diabetes mellitus 180 days or more before screening.
• HbA1c of 7.0-10.0 percentage (53.- 85.8 mmol/mol) (both inclusive) as assessed by central laboratory on the day of screening.

• Treated with once daily or twice-daily basal insulin (neutral protamine hagedorn insulin, insulin degludec, insulin detemir, insulin glargine 100 units/mL, or insulin glargine 300 units/mL) 20-80 units/day 90 days or more before screening. Short term bolus insulin treatment for a maximum of 14 days before screening is allowed, as is prior insulin treatment for gestational diabetes. The treatment can be with or without any of the following anti diabetic drugs with stable doses 90 days or more before screening:

  • Metformin
  • Sulfonylureas(a)
  • Meglitinides (glinides)(a)
  • DPP-4 inhibitors(a)
  • 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 kg/m^2.

  1. Sulfonylureas, meglitinides (glinides) and DPP-4 inhibitors must be discontinued at randomisation.

Exclusion Criteria:

• 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 of diabetic ketoacidosis within 90 days before screening. As declared by the participant or in the medical records.
• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IcoSema; Participants will receive once weekly subcutaneous (s.c) injections of IcoSema during the 52-week treatment period.	Drug: IcoSema; Participants will receive a once weekly subcutanous (s.c.) injection of IcoSema, on the same day every week for 52 weeks.
Active Comparator: Insuling glargine/insulin aspart; Participants will receive subcutaneous (s.c) injections of insulin glargine once daily combined with 2-4 times daily injections of insulin aspart.	Drug: Insulin glargine; Participants will receive a once daily subcutaneous (s.c.) injection of insulin glargine combined with Insulin aspart 2-4 times a day during mealtimes for 52 weeks.; Drug: insulin aspart; Participants will receive a once daily subcutaneous (s.c.) injection of insulin glargine combined with Insulin aspart 2-4 times a day during mealtimes for 52 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c	Percent-points	From baseline week 0 (V2) to week 52 (V54)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight	Kg	From baseline week 0 (V2) to week 52 (V54)
Number of severe hypoglycaemic episodes (level 3)	Number of episodes	From baseline week 0 (V2) to week 57 (V56)
Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)	Number of episodes	From week 0 (V52) to week 52 (V54)
Time in range 3.9 - 10.0 mmol/L (70 - 180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	Percentage of readings	From week 48 (V50) to week 52 (V54)
Time spent more than 10.0 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	Percentage of readings	From week 48 (V50) to week 52 (V54)
Time spent less than 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6	Percentage of readings	From week 48 (V50) to week 52 (V54)
Change in fasting plasma glucose (FPG)	mmol/L	From baseline week 0 (V2) to week 52 (V54)
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in total treatment satisfaction	Score 0-36. The higher the score the greater the satisfaction with treatment.	From baseline week 0 (V2) to week 52 (V54)
Number of clinically significant hypoglycaemic episodes (level 2) (less than 3.0 mmol/L (54 mg/dL), confirmed by BG meter)	Number of episodes	From baseline week 0 (V2) to week 57 (V56)
Weekly insulin dose (total)	Units	From week 50 (V52) to week 52 (V54)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Publications and helpful links

General Publications

• Billings LK, Andreozzi F, Frederiksen M, Gourdy P, Gowda A, Ji L, Pletsch-Borba L, Suzuki R, Unnikrishnan AG, Vianna AGD. Once-weekly IcoSema versus multiple daily insulin injections in type 2 diabetes management (COMBINE 3): an open-label, multicentre, treat-to-target, non-inferiority, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2025 Jul;13(7):556-567. doi: 10.1016/S2213-8587(25)00052-X. Epub 2025 Jun 4.

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2021
• Primary Completion (Actual): November 14, 2023
• Study Completion (Actual): November 14, 2023

Study Registration Dates

• First Submitted: August 13, 2021
• First Submitted That Met QC Criteria: August 13, 2021
• First Posted (Actual): August 19, 2021

Study Record Updates

• Last Update Posted (Estimated): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting; Insulins; Pancreatic Hormones; Insulin, Short-Acting; Insulin Glargine; Insulin Aspart
• Other Study ID Numbers: NN1535-4593; U1111-1260-8295 (Other Identifier: WHO); 2020-005309-18 (EudraCT Number); jRCT2051210127 (Registry Identifier: JAPIC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No