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NCT06269107CompletedPhase 3

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)

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

Source: ClinicalTrials.gov · Last updated 5 Jun 2026

Brief summary (registry, in English)

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).

Status (registry)
Completed
Phase (registry)
Phase 3
Study type
Interventional
Enrollment
485 (actual)
First submitted
13 Feb 2024
Start date
15 Feb 2024
Primary completion date
27 May 2025
Lead sponsor
Novo Nordisk A/S
NCT number
NCT06269107
EU CT number
2022-502484-38-00

What you commit to

  • Study type: Interventional · Phase 3
  • Participants enrolled: 485
  • From 15 Feb 2024 to the primary completion date, 27 May 2025
  • 114 sites in 10 countries
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

  • 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.
  • 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.

Other illness

  • Chronic heart failure classified as being in New York Heart Association Class IV at screening.

Lab values

  • 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).

Other

  • Female who is pregnant, breast-feeding or intends to become pregnant or is of childbaring potential and not using highly effective contraceptive method.
  • Recurrent severe hypoglycaemic episodes within the last year (12 months) as judged by the investigator.

Who the study is looking for

  • 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).

Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (114)

Sites in registry order. Pick your city on the disease page to sort them by distance.

SiteCityCountrySite status
Beijing Friendship Hospital, Capital Medical University-Endocrinology
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BeijingChinaUnknown status
Peking University People's Hospital-Endocrinology
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BeijingChinaUnknown status
Chongqing University Three Gorges Hospital
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ChongqingChinaUnknown status
Hengshui People's Hospital (Harrison International Peace Hospital)-Endocrinology
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HengshuiChinaUnknown status
Huizhou Central People's Hospital-Endocrinology
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HuizhouChinaUnknown status
Jinan Central Hospital
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JinanChinaUnknown status
The Second Affiliated Hospital of Nanjing Medical University
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NanjingChinaUnknown status
Shanghai Pudong New Area People's Hospital-Endocrinology
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ShanghaiChinaUnknown status
The Affiliated Hospital of Jiangsu University
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ZhenjiangChinaUnknown status
Laiko General Hospital of Athens
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AthensGreeceCompleted
Evangelismos S A
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AthensGreeceCompleted
General Hospital of Athens "G. Gennimatas"
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AthensGreeceCompleted
General Hospital Of Messinia
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KalamataGreeceCompleted
General University Hospital of Larissa
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LarissaGreeceCompleted
Thermi Clinic S.A.
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ThessalonikiGreeceCompleted
Ramaiah Memorial Hospital
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BangaloreIndiaUnknown status
Sai A Health Wellness LLP
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BangaloreIndiaUnknown status
Post Graduate Institute of Medical Education & Research,
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ChandigarhIndiaUnknown status
Madras Diabetes Research Foundation
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ChennaiIndiaUnknown status
Goa Medical College
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GoaIndiaUnknown status
CHL Hospitals
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IndoreIndiaUnknown status
Diabetes, Thyroid and Endocrine Centre
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JaipurIndiaUnknown status
SMS Medical College & Hospital
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JaipurIndiaUnknown status
IPGME&R and SSKM Hospital
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KolkataIndiaUnknown status
METTA Clinic (a unit of Healious Global Pvt. Ltd.)
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KolkataIndiaUnknown status
Udyaan Health Care
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LucknowIndiaUnknown status
BYL Nair Hospital and T N Medical College Department of endo
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MumbaiIndiaUnknown status
BSES MG hospital
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MumbaiIndiaUnknown status
Seth GS Medical College & KEM Hospital
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MumbaiIndiaUnknown status
Mysore Medical College and Research Institute
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MysoreIndiaUnknown status
Chellaram Diabetes Institute
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PuneIndiaUnknown status
I.N.R.C.A. Istituto Nazionale di Riposo E Cura Per Gli Anziani
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AnconaItalyCompleted
Casa della Salute
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Ceccano, (FR)ItalyCompleted
Azienda Sociosanitaria Ligure N 4 Sistema Sanitario Regione Liguria
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ChiavariItalyCompleted
ASL1 Abruzzo, Dipartimento Medico, Ospedale San Salvatore
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L'AquilaItalyCompleted
ASST Grande Ospedale Metropolitano Niguarda
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MilanItalyCompleted
Hospital Santa Maria Della Misericordia
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PerugiaItalyCompleted
Azienda Ospealiero Universitaria Policlinico Umberto I
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RomeItalyCompleted
Casa Sollievo della Sofferenza
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San Giovanni RotondoItalyCompleted
Tokuyama clinic_Diabetic internal medicine
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ChibaJapanUnknown status
Oodouri Diabetes, Internal medicine Clinic_Internal Medicine, Diabetes Internal Medicine
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HokkaidoJapanUnknown status
Heiwadai Hospital_Internal Medicine
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MiyazakiJapanUnknown status
Oyama East Clinic_Internal Medicine
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TochigiJapanUnknown status
Fukuwa Clinic_Internal Medicine
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TokyoJapanUnknown status
Tokyo-Eki Center-building Clinic_Internal Medicine
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TokyoJapanUnknown status
Juntendo University Hospital_Diabetes, endocrinology and metabolism
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TokyoJapanUnknown status
Legeartis Poradnie Specjalistyczne Sp. z o.o.
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BialystokPolandCompleted
Nzoz Specjalistyczny Osrodek Internistyczno-Diabetologiczny Malgorzata Arciszewska
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BialystokPolandCompleted
Centrum Medyczne All-Med Badania Kliniczne
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CracowPolandCompleted
Uniwersyteckie Centrum Kliniczne
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GdanskPolandCompleted
Gabinet Lekarski Malgorzata Saryusz-Wolska
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LodzPolandCompleted
Centrum Terapii Wspolczesnej J.M. Jasnorzewska S.K.A.
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LodzPolandCompleted
Velocity Nova Sp. z o.o.
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LublinPolandCompleted
Velocity Nova Sp. z o.o.
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StaszowPolandCompleted
Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych i Administracji
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WarsawPolandCompleted
NBR POLSKA TOMASZ KLODAWSKI
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WarszawaPolandCompleted
Clinhouse Sp. z o.o.
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ZabrzePolandCompleted
Advanced Clinical Research, LLC
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BayamónPuerto RicoUnknown status
AMC Community Endocrinology
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AlbanyUnited StatesUnknown status
Albuquerque Clin Trials, Inc.
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AlbuquerqueUnited StatesUnknown status
Amarillo Med Spec LLP
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AmarilloUnited StatesUnknown status
Atlanta Diabetes Associates
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AtlantaUnited StatesUnknown status
Velocity Clinical Research- Cedar Park
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AustinUnited StatesUnknown status
Univ of Alabama Birmingham
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BirminghamUnited StatesUnknown status
Elite Clinical Trials
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BlackfootUnited StatesUnknown status
Wade Family Medicine
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BountifulUnited StatesUnknown status
Diab & Endo Assoc of Stark Co
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CantonUnited StatesUnknown status
Cedar Crosse Research Center
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ChicagoUnited StatesUnknown status
John Muir Physicians Network
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ConcordUnited StatesUnknown status
Velocity Clinical Res-Dallas
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DallasUnited StatesUnknown status
North Texas Endocrine Center
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DallasUnited StatesUnknown status
Northeast Research Institute
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Fleming IslandUnited StatesUnknown status
Diabetes and Thyroid Ctr of FW
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Fort WorthUnited StatesUnknown status
PharmQuest Life Sciences LLC
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GreensboroUnited StatesUnknown status
Physician's East Endocrinology
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GreenvilleUnited StatesUnknown status
East West Medical Research Institute_Honolulu
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HonoluluUnited StatesUnknown status
East Coast Institute for Research
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JacksonvilleUnited StatesUnknown status
Holston Medical Group.
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KingsportUnited StatesUnknown status
Scripps Whittier Diabetes Inst
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La JollaUnited StatesUnknown status
Fmc Science, Llc
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LampasasUnited StatesUnknown status
First Valley Med Grp Lancaster
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LancasterUnited StatesUnknown status
The Research Group of Lexington LLC
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LexingtonUnited StatesUnknown status
Clinical Trials Research_Sacramento
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LincolnUnited StatesUnknown status
Advanced Medical Research
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MaumeeUnited StatesUnknown status
TPMG Clinical Research
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Newport NewsUnited StatesUnknown status
Methodist Phys. Clinic
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OmahaUnited StatesUnknown status
Desert Oasis Hlthcr Med Group
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Palm SpringsUnited StatesUnknown status
Epic Medical Research
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Red OakUnited StatesUnknown status
Endo and Metab Consultants
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RockvilleUnited StatesUnknown status
Endo Res Solutions Inc
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RoswellUnited StatesUnknown status
Flourish Research
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San AntonioUnited StatesUnknown status
Quality Research Inc
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San AntonioUnited StatesUnknown status
Consano Clinical Research, LLC
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Shavano ParkUnited StatesUnknown status
Endeavor Health
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SkokieUnited StatesUnknown status
Simcare Medical Research, LLC
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Sugar LandUnited StatesUnknown status
Cotton O'Neil Diab & Endo Ctr
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TopekaUnited StatesUnknown status
Essential Medical Research LLC
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TulsaUnited StatesUnknown status
New Venture Medical Research
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WadsworthUnited StatesUnknown status
Southgate Medical Group, LLP
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West SenecaUnited StatesUnknown status
Clinical Research of Cent FL
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Winter HavenUnited StatesUnknown status
Langeberg Clinical Trials
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Cape TownSouth AfricaUnknown status
Dr Pillay's Rooms
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DurbanSouth AfricaUnknown status
Newtown Clinical Research
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JohannesburgSouth AfricaUnknown status
Dr R Dulabh
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JohannesburgSouth AfricaUnknown status
Clinical Research Institute of South Africa
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KwaDukuzaSouth AfricaUnknown status
Roodepoort Medicross Clinical Research Centre
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RoodepoortSouth AfricaUnknown status
Akdeniz Üniversitesi Hastanesi- Endokrinoloji
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AntalyaTurkey (Türkiye)Unknown status
Akdeniz University Tip Fakultesi Hastanesi
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AntalyaTurkey (Türkiye)Unknown status
Seyrantepe Hamidiye Etfal Egitim ve Arastirma Hastanesi
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IstanbulTurkey (Türkiye)Unknown status
İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Endokrinoloji
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IstanbulTurkey (Türkiye)Unknown status
Başakşehir Çam ve Sakura Şehir Hastanesi
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IstanbulTurkey (Türkiye)Unknown status
Şişli Hamidiye Etfal Eğitim ve Araştırma Hastanesi- Seyrantepe Yerleşkesi- Endokrinoloji
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IstanbulTurkey (Türkiye)Unknown status
T.C. Saglik Bakanligi Pendik Egitim ve Arastirma Hastanesi
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IstanbulTurkey (Türkiye)Unknown status
Tekirdağ Namık Kemal Üniversitesi Hastanesi- Dahiliye
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TekirdağTurkey (Türkiye)Unknown status

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This page is information, not medical advice. Discuss any trial with your doctor.