CAROLINA: Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes

A Multicentre, International, Randomised, Parallel Group, Double Blind Study to Evaluate Cardiovascular Safety of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk.

The aim of the study is to investigate the longterm impact on cardiovascular morbidity and mortality, relevant efficacy parameters (e.g., glycaemic parameters) and safety (e.g., weight and hypoglycaemia) of treatment with linagliptin in patients with type 2 diabetes at elevated cardiovascular risk receiving usual care, and compare outcome against glimepiride.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: linagliptin; Drug: glimepiride placebo; Drug: glimepiride; Drug: linagliptin placebo

• Study Type: Interventional
• Enrollment (Actual): 6103
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Bahía Blanca, Argentina, B8000FTD
    • Instituto de Investigaciones Clinicas de Bahia Blanca
  • Caba, Argentina, C1119ACN
    • CIPREC
  • Caba, Argentina, C1440AAD
    • CENUDIAB
  • Capital Federal, Argentina, C1405BCH
    • Instituto Médico Especializado
  • Capital Federal, Argentina, C1425AGC
    • Consultorios Asociados de Endocrinología e Invest Clínica
  • Cordoba, Argentina, X5008KKF
    • IPAC - Clínica Privada Caraffa SRL
  • Corrientes, Argentina, W3400AMZ
    • Instituto Cardiovascular de Corrientes Juana Francisca Cabra
  • Córdoba, Argentina, X5000BNB
    • Ilaim-Ceom
  • La Plata, Argentina, B1900AWT
    • Hospital Italiano de la Plata
  • Mendoza, Argentina, M5500EVJ
    • CIPADI
  • Rosario, Argentina, S2000CVD
    • Instituto de Investigaciones Clinicas de Rosario
  • Rosario, Argentina, S2000CXP
    • Instituto de Hematología y Medicina Clínica Dr. Rubén Dávoli
  • Salta, Argentina, A4406CLA
    • Hospital San Bernardo
  • San Miguel de Tucumán, Argentina, T4000ICL
    • Investigaciones Clínicas Tucumán
  • Santa Fe, Argentina, S3000FNF
    • Instituto de Investigaciones Biomedicas
  • Santa Fe, Argentina, S3000SWO
    • Centro de Investigaciones Clinicas del Litoral
• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital-Endocrinology
    • Meadowbrook, Queensland, Australia, 4131
      • Logan Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • East Ringwood, Victoria, Australia, 3135
      • Eastern Clinical Research Unit
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Belgium
  • Blankenberge, Belgium, 8370
    • Blankenberge - PRAC Vileyn, Geert
  • Bonheiden, Belgium, 2820
    • Bonheiden - HOSP Imelda
  • De Pinte, Belgium, 9840
    • De Pinte - PRAC Hollanders, Geert
  • Dessel, Belgium, 2480
    • Retie - PRAC De Vos, Axel
  • Deurne, Belgium, 2100
    • Deurne - PRAC Heyvaert, Frank
  • Deurne, Belgium, 2100
    • Deurne - PRAC Verelst, Joost
  • Genk, Belgium, 3600
    • Genk - PRAC Vernijns, J.
  • Gozée, Belgium, 6534
    • Gozée - PRAC De Meulemeester, Marc
  • Hasselt, Belgium, 3500
    • Hasselt - PRAC Vantroyen, Daniel
  • Herent, Belgium, 3020
    • Herent - PRAC Denolf, Bart
  • Linkebeek, Belgium, 1630
    • Linkebeek - PRAC Maury, Olivier
  • Moorsel, Belgium, 9310
    • Moorsel - PRAC Van Mulders, N.
  • Natoye, Belgium, 5360
    • Natoye - PRAC Balthazar, Y.
  • Tremelo, Belgium, 3210
    • Tremelo - PRAC Vermeersch, Lode
• Brazil
  • Belém, Brazil, 66073-000
    • Hospital Universitário João de Barros Barreto
  • Curitiba, Brazil, 80060-900
    • Universidade Federal do Parana
  • Goiânia, Brazil, 74043-110
    • Hospital Geral de Goiânia Alberto Rassi
  • Higienópolis, Brazil, 01244-030
    • Centro de Pesquisas Clínicas Ltda
  • Joaquim Távora, Brazil, 60115-282
    • Centro de Estudos em Diabetes e Hipertensão
  • Porto Alegre, Brazil, 90020-090
    • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Porto Alegre, Brazil, 90035-170
    • Centro de Pesquisas em Diabetes
  • Río de Janeiro, Brazil, 20211-340
    • Instituto Estadual de Diabetes e Endocrinologia
  • Santa Cecília, Brazil, 01221-020
    • Irmandade da Santa Casa de Misericórdia de São Paulo - IPEC - Instituto de Pesquisa Clínica
  • São José do Rio Preto, Brazil, 15015-210
    • Instituto de Molestias Cardiovasculares - IMC
  • São Paulo, Brazil, 05403-900
    • Hospital das Clinicas da FMUSP
  • Vila Clementino, Brazil, 04025-011
    • Hospital do Rim e Hipertensão - UNIFESP
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Univ.Multiprofile Hospital "Dr. Georgy Stranski" EAD, Pleven
  • Sofia, Bulgaria, 1431
    • Multiprofile hospital for active treatment
  • Sofia, Bulgaria, 1527
    • Multiprofile Hospital for Active Treatment "Zaritza Johanna"
  • Sofia, Bulgaria, 1606
    • Military Medical Academy, Clin. Endocrinology & Metab. Dis.
  • Stara Zagora, Bulgaria, 6000
    • MHAT Prof Stoyan Kirkovich AD
• Canada
  • Migration Data
    • Quebec, Migration Data, Canada, G1V 4G5
      • IUCPQ (Laval University)
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1E 2E2
      • Topsail Road Medical Clinic
    • St. John's, Newfoundland and Labrador, Canada, A1E 2C2
      • First Line Medical Services Ltd.
  • Ontario
    • Cambridge, Ontario, Canada, N1R 6V6
      • Cambridge Cardiac Care Inc.
    • Hamilton, Ontario, Canada, L8M 1K7
      • Hamilton Medical Research Group
    • Newmarket, Ontario, Canada, L3Y 5G8
      • SKDS Research Incorporated
    • Thornhill, Ontario, Canada, L4J 1W3
      • Wilderman Medical Clinic
    • Toronto, Ontario, Canada, M5C 2T2
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M9V 4B4
      • Albion Finch Medical Centre
  • Prince Edward Island
    • Montague, Prince Edward Island, Canada, C0A 1R0
      • Kings County Medical Centre
  • Quebec
    • Pointe Claire, Quebec, Canada, H9R 3J1
      • Dynamik Research
• Chile
  • Providencia, Chile, 7500010
    • Consulta Privada Maria Loreto Aguirre Coveña
  • Providencia, Chile
    • Hospital de Servicios Médicos Godoy Ltda
  • Temuco, Chile
    • Centro Medico Antulawen
  • Viña del Mar, Chile
    • Hospital Naval Almirante Nef
• Colombia
  • Barranquilla, Colombia
    • BIOMELAB
  • Barranquilla, Colombia
    • Centro Cientifico Asistencial Jose Luis Accini
  • Barranquilla, Colombia
    • Fundacion del Caribe de Investigacion Biomedica
  • Bogota, Colombia
    • Endocare Research Institute
  • Bogotá, Colombia
    • Dexa Diabetes Servicios Médicos Ltda
  • Bogotá, Colombia
    • UNIENDO Unidad Integral de Endocrinologia
  • Cartagena, Colombia
    • Centro cardiovascular Aristides
  • Cartagena, Colombia
    • centro de Diagnostico Cardiologico para la Investigacion Bio
  • El Bosque, Colombia
    • Fundacion Cardiovascular de Colombia
  • El Bosque, Colombia
    • Fundacion Oftalmologica De Santander
  • Tolima, Colombia
    • Fundación Centro de Investigaciones Biomédicas Riescard
• Czechia
  • Jablonec nad Nisou, Czechia, 466 01
    • Internal & Diabetology Ambulance, Jablonec nad Nisou
  • Olomouc-Lazce, Czechia, 779 00
    • Diabetology & Internal Ambulance
  • Ostrava, Czechia, 702 00
    • Internal & Diabetology Ambulance Dr. Vrkoc, Ostrava
  • Plzen, Czechia, 301 00
    • Cardiology ambulance, Plzen
  • Praha, Czechia, 101 00
    • Diebetology internal Ambulance
  • Praha 8, Czechia, 181 00
    • ResTrial s.r.o.
  • Prostejov, Czechia, 796 01
    • Internal & Diabetology Ambulance, Prostejov
  • Strakonice, Czechia, 386 29
    • Hospital Strakonice, Internal Department
• Finland
  • Helsinki, Finland, 00260
    • Diabetesklinikka, Mehiläinen Töölö
  • Joensuu, Finland, 80100
    • Lääkärikeskus Ite
  • Kerava, Finland, 04200
    • Lääkärikeskus Aava Kerava
  • Kokkola, Finland, 67100
    • Kokkolan Lääkärikeskus
  • Kuopio, Finland, FI-70100
    • IteLasaretti
  • Oulu, Finland, FI-90100
    • Terveystalo Oulu, Diapolis
  • Turku, Finland, FI-20520
    • TYKS
• France
  • Behren Les Forbach, France, 57460
    • CAB Hell M, MG, Behren Les Forbach
  • Bordeaux, France, 33075
    • HOP Haut Levèque, Diabéto, Pessac
  • Bourg des Comptes, France, 35890
    • CAB Lemarie B, MG, Bourg des Cptes
  • Broglie, France, 27270
    • CAB Cadinot Dr D, Broglie
  • Béziers, France, 34500
    • CAB Breton Dr Nicolas
  • Cannes, France, 06400
    • CAB Ferrier R, MG, Cannes
  • Carbonne, France, 31390
    • CAB Jordan E, MG, Carbonne
  • Castets, France, 40260
    • CAB Merlin P, MG Castets
  • Chartres, France, 28000
    • CAB Fonteny R, MG, Chartres
  • Chartres, France, 28000
    • CAB Fournier P, MG, Chartres
  • Cournonterral, France, 34660
    • CAB Martocq G, MG, Cournonterral
  • Fort De France, France, 97261
    • HOP, Fort de France, Fort de France
  • Hinx, France, 40180
    • CAB Le Mouel S, MG, Hinx
  • La Reunion, France, 97410
    • CAB Pholsena, MG, La Réunion
  • Labarthe sur Leze, France, 31860
    • CAB Bismuth M
  • Louvigne De Bie, France, 35680
    • CAB Zimmermann D
  • Maintenon, France, 28130
    • CAB Mainetti P, MG, Maintenon
  • Orthez, France, 64300
    • CAB Barucq F, MG, Orthez
  • Orthez, France, 64300
    • CAB Mostephai M
  • Palau Del Vidre, France, 66690
    • CAB Cassagnes JL, MG, Palau Del Vidre
  • Saint Genies Des Fontaines, France, 66740
    • CAB Mercey Y, MG, St Genies des Fontaines
  • St Dié des Vosges Cedex, France, 88187
    • Hop St Dié des Vosges, Diabéto, St Dié des Vosges
  • Thouars, France, 79100
    • CAB Bonneau D, MG, Thouars
  • Tilly sur Seulles, France, 14250
    • CAB Morel H, MG, Tilly sur Seulles
• Georgia
  • Batumi, Georgia, 6004
    • Unimed Ajara LLC, Private Practice
  • Gori, Georgia, 1400
    • Central Hospital LTD 'Gormedi', Gori
  • Kutaisi, Georgia, 4600
    • L&J Clinic, Kutaisi
  • Tbilisi, Georgia, 0144
    • EC Cardiology Clinic,Tbilisi
  • Tbilisi, Georgia, 0159
    • National Center for Diabetes Research Ltd., Tbilisi
  • Tbilisi, Georgia, 0159
    • National Institute of Endocrinology, Tbilisi
  • Tbilisi, Georgia, 0159
    • Zhordania Institute of Human Reproduction, Tbilisi
  • Tbilisi, Georgia, 0177
    • Medical Centre Medelite Ltd., Tbilisi
  • Tbilisi, Georgia, 0186
    • Chemotherapy & Immunotherapy Clinic 'Medulla', Tbilisi
  • Zugdidi, Georgia, 2100
    • JSC 'Curatio'
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen, AöR
  • Aschaffenburg, Germany, 63739
    • Studienzentrum Klausmann
  • Asslar, Germany, 35614
    • Gemeinschaftspraxis, Asslar
  • Bad Nauheim, Germany, 61231
    • Diabetes Schwerpunktpraxis
  • Berlin, Germany, 10629
    • emovis GmbH
  • Berlin, Germany, 10789
    • Praxis Dr. Rieker, Berlin
  • Berlin, Germany, 10409
    • Praxis Dr. Naumburger, Berlin
  • Berlin, Germany, 12621
    • IFG Institut für Gesundheitsförderung GmbH
  • Dormagen- Hackenbroich, Germany, 41540
    • MVZ DaVita Dormagen GmbH
  • Dortmund, Germany, 44137
    • Praxis Dr. Busch, Dortmund
  • Dresden, Germany, 01307
    • GWT-TUD GmbH
  • Eisenach, Germany, 99817
    • Praxis Dr. Schlecht, Eisenach
  • Elsterwerda, Germany, 04910
    • ZKS Südbrandenburg GMBH
  • Essen, Germany, 45307
    • Praxis Dr. Huptas, Essen
  • Flörsheim, Germany, 65439
    • Praxis Dr. Schmidt, Flörsheim
  • Frankfurt, Germany, 60322
    • Institut für Stoffwechselforschung, Frankfurt
  • Furth im Wald, Germany, 93437
    • Praxis Dr. Groeneveld, Furth im Wald
  • Gebhardshain, Germany, 57580
    • Praxis Dr. Kohlhas, Gebhardshain
  • Haag, Germany, 83527
    • Praxis Dr. Samer, Haag
  • Hamburg, Germany, 20253
    • Klinische Forschung Management & Services GmbH
  • Hamburg, Germany, 21073
    • Diabetologische Schwerpunktpraxis
  • Hamburg, Germany, 22335
    • Praxis Dr. Burkhardt, Hamburg
  • Hamburg, Germany, 22391
    • Diabeteszentrum Alstertal, Hamburg
  • Kirchhatten, Germany, 26209
    • Praxis Dr. Herrmann, Hatten
  • Köln, Germany, 51069
    • Dünnwaldpraxis, Köln
  • Künzing, Germany, 94550
    • Praxis Dr. Klein, Künzing
  • Leipzig, Germany, 04109
    • Praxis Dr. Nischik, Leipzig
  • Lübeck, Germany, 23554
    • Praxis Dr. Kropp, Lübeck
  • Mainz, Germany, 55128
    • Pfützner Science & Health Institute GmbH
  • Münster, Germany, 48153
    • Diabetologische Schwerpunktpraxis
  • Neumünster, Germany, 24534
    • Praxis Dr. Böckmann
  • Rehburg-Loccum, Germany, 31547
    • Praxis Dr. Hilgenberg
  • Rodgau/Dudenhofen, Germany, 63110
    • Praxis Dr. Naudts, Rodgau
  • Saarbrücken, Germany, 66121
    • Praxis Dr. Hirschhäuser
  • Saint Ingbert / Oberwürzbach, Germany, 66386
    • Praxis Dr. Segner, St. Ingberg
  • Schwabenheim, Germany, 55270
    • Praxis Dr. Herrmann
  • Stadtbergen, Germany, 86391
    • Praxis Dr. Dietlein
  • Wangen, Germany, 88239
    • Praxis Dr. Sauter
  • Zwenkau, Germany, 04442
    • Schwerpunktpraxis Diabetologie
• Greece
  • Athens, Greece, 10676
    • General Hospital of Athens Evangelismos
  • Haidari, Athens, Greece, 12410
    • General University Hospital "Attikon"
  • Ioannina, Greece, 45500
    • Univ. Gen. Hosp. of Ioannina
  • Melissia, Athens, Greece, 15127
    • General Hospital "Amalia Fleming"
  • Nikaia, Greece, 18484
    • General Hospital of Nikaia
  • Thessaloniki, Greece, 54642
    • General Hopsital of Thessaloniki "Ippokrateio"
  • Thessaloniki, Greece, 54636
    • University General Hospital of Thessaloniki AHEPA
  • Thessaloniki, Greece, 57001
    • Kliniki Thermi
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
  • Hong Kong, Hong Kong
    • Alice Ho Miu Ling Nethersole Hospital
• Hungary
  • Ajka, Hungary, 8400
    • Imre Magyar Hospital, Ajka
  • Baja, Hungary, 6500
    • Lausmed Kft. Outpatient Unit of Internal Medicine
  • Budapest, Hungary, 1041
    • Karolyi Sandor Hospital, Budapest
  • Gyula, Hungary, 5700
    • Bekes County Pandy Kalman Hospital
  • Hódmezövásárhely, Hungary, 6800
    • Erzsebet Hospital, Hodmezövasarhely
  • Mako, Hungary, 6900
    • Dr. Samuel Diosszilagyi Hospital and Outpatient Clinic, Mako
  • Mosonmagyarovar, Hungary, 9200
    • TaNa Med Kft.
  • Papa, Hungary, 8500
    • Grof Esterhazy Hospital and Outpatient Clinic
  • Szekszard, Hungary, 7100
    • Tolna County Balassa János Hospital
• India
  • Ahmedabad, India, 380052
    • Shree Krishna Hospital and Heart Care Centre, Ahmedabad
  • Aurangabad, India, 431001
    • CIIGMA Institute of Medical Sciences Pvt Ltd
  • Bangalore, India, 560017
    • Manipal Hospital
  • Bangalore, India, 560010
    • Diabetes Care and Research Centre
  • Bangalore, India, 560043
    • Bangalore Diabetes Centre (BDC)- Medisys Clinical Research
  • Bangalore, Karnataka, India, 560054
    • MS Ramaiah Memorial Hospital,
  • Belgaum, India, 590001
    • Belgaum Diabetes Centre, Belgaum
  • Chennai, India, 600 028
    • Swamy Diabetes Centre
  • Chennai, India, 600010
    • Apollo Hospitals
  • Chennai, India, 600013
    • M V Hospital For Diabetes and Diabetes Research Centre
  • Chennai, India, 600086
    • Dr. Mohans Diabetes Speciality Centre
  • Coimbatore, India, 641009
    • Kovai Diabetes Speciality Centre & Hospital
  • Indore, India, 452010
    • TOTALL Diabetes Hormone Institute
  • Jaipur, India, 302 006
    • Diabetes Thyroid and Endocrine Centre
  • Jaipur, India, 302016
    • Diamed Clinical Research Services Pvt. Ltd.
  • Maharashtra, India, 411001
    • Grant Medical Foundation, Ruby Hall Clinic
  • Mumbai, India, 400012
    • Global Hospital- Superspeciality & Transplant Centre
  • Mumbai, India, 400014
    • RHIDEM
  • Mumbai, Maharastra, India, 400008
    • K.G.N. Diabetes and Endocrine Centre
  • Nagpur, India, 440 010
    • Sunil's Diabetes care and Research Centre
  • Pune, India, 411001
    • Jahingir Clinical Development Centre
  • Pune, India, 411030
    • Deshmukh Clinic
  • Thiruvananthapuram, India, 695 010
    • Diabetes Care Center
  • Vijayawada, India, 520 002
    • Yalamanchi Hospitals & Research Centres Pvt Ltd.
• Ireland
  • Co. Cork, Ireland, CORK
    • The Red House Family Practice
  • Dublin, Ireland, 15
    • Connolly Hospital Blanchardstown
  • Gorey, Ireland, Wexford
    • The Palms GP Surgery
  • Wexford, Ireland, Wexford
    • Fethard-on-Sea Medical Practice
• Israel
  • Ashkelon, Israel, 78278
    • Barzilai Medical Center
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Holon, Israel, 58100
    • Edith Wolfson Medical Center, Diabetic Unit, Holon
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center, Ein-Karem
  • Nahariya, Israel, 22100
    • Western Galilee Hospital
  • Tel Hashomer, Israel, 52621
    • The Chaim Sheba Medical Center Tel HaShomer
  • Tel-Aviv, Israel, 64239
    • Sourasky Medical Center
• Italy
  • Cagliari, Italy, 09100
    • Ospedale "SS. Trinità"
  • Catanzaro, Italy, 88100
    • Policlinico Universitario Mater Domini, Universita di Catanzaro
  • Genova, Italy, 16132
    • Policlinico San Martino
  • Guastalla (RE), Italy, 42016
    • Ospedale di Guastalla
  • Messina, Italy, 98125
    • A.O.U.Policlinico G.Martino
  • Milano, Italy, 20132
    • Fondazione Centro San Raffaele del Monte Tabor
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
  • Roma, Italy, 00100
    • Ospedale S. Pertini
  • Sesto San Giovanni (MI), Italy, 20099
    • IRCCS Gruppo Multimedica
• Japan
  • Aichi, Nagoya, Japan, 462-0825
    • Daishinkai Medical Corporation Ookuma Hospital
  • Chiba, Matsudo, Japan, 270-2251
    • Chibanishi General Hospital
  • Chiba, Matsudo, Japan, 271-0077
    • New Tokyo Heart Clinic
  • Fukushima, Date, Japan, 960-0418
    • Kashinoki I.M. Clinic, Fukushima, I.M.
  • Fukushima, Nihonmatsu, Japan, 964-8501
    • Japan Community Health care Organization Nihonmatsu hospital
  • Fukushima, Sukagawa, Japan, 962-8503
    • Iwase General Hospital
  • Hyogo, Amagasaki, Japan, 660-0827
    • Iryohojinshadan Sasaki Clinic
  • Hyogo, Takasago, Japan, 676-0812
    • Takasagoseibu Hospital
  • Kanagawa, Yokohama, Japan, 236-0051
    • Kanagawa Cardiovascular and Respiratory Center
  • Kumamoto, Kumamoto, Japan, 862-0976
    • Jinnouchi Clinic Diabetes Care Center
  • Kumamoto, Yatsushiro, Japan, 866-8533
    • Kumamoto Rosai Hospital
  • Miyazaki, Miyazaki, Japan, 880-0041
    • Koga General Hospital
  • Saitama, Hanyu, Japan, 348-0045
    • Saitama Medical Cooperative Association Hanyu General Hospital
  • Tokyo, Itabashi-ku, Japan, 173-8610
    • Nihon University Itabashi Hospital
• Korea, Republic of
  • Ansan, Korea, Republic of, 15355
    • Korea University Ansan Hospital
  • Busan, Korea, Republic of, 614-735
    • Inje University Busan Paik Hospital
  • Daegu, Korea, Republic of, 700-712
    • Keimyung University Dongsan Medical Center
  • Goyang, Korea, Republic of, 411-706
    • Inje University Ilsan Paik Hospital
  • Goyang, Korea, Republic of, 410-773
    • DongGuk University ilsan Hospital
  • Goyang, Korea, Republic of, 410-719
    • National Health Insurance Service Ilsan Hospital
  • Jeonju, Korea, Republic of, 561-712
    • Chonbuk National University Hospital
  • Pusan, Korea, Republic of, 602-739
    • Pusan National Univ. Hosp
  • Seongnam, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 134-701
    • Kangdong Sacred Heart Hospital
  • Suwon, Korea, Republic of, 443-380
    • Ajou University Hospital
  • Wonju, Korea, Republic of, 220-701
    • Wonju Severance Christian Hosp
  • Yangsan, Korea, Republic of, 626-770
    • Pusan National University Yangsan Hospital
• Malaysia
  • Johor Bahru, Johor, Malaysia, 80100
    • Monash University
  • Kota Bharu, Malaysia, 16150
    • Hospital University Sains Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
  • Kuantan, Malaysia, 25100
    • Hospital Tengku Ampuan Afzan
  • Melaka, Malaysia, 75400
    • Hospital Melaka
  • Penang, Malaysia, 10450
    • Penang Medical College
  • Taiping, Malaysia, 34000
    • Hospital Taiping
• Mexico
  • Acapulco, Mexico, 39570
    • Hospital General de Acapulco
  • Aguascalientes, Mexico, 20234
    • Centro de Investigación Cardiometabólica de Aguascalientes
  • Distrito Federal, Mexico, 14080
    • Instituto Nacional de Cardiologia Ignacio Chavez
  • Guadalajara, Mexico, 44150
    • Unidad de Investigacion Clinica Cardiometabolica de Occident
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr Jose Eleuterio Gonzalez
• Netherlands
  • 's-hertogenbosch, Netherlands, 5235 KG
    • Huisartspraktijk Emmers
  • Almere, Netherlands, 1311 RL
    • FlevoResearch
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum (AMC)
  • Beverwijk, Netherlands, 1942 LE
    • Rode Kruis Ziekenhuis Beverwijk
  • Breda, Netherlands, 4811 SW
    • Andromed Breda
  • Den Helder, Netherlands, 1782 GZ
    • Noordwest Ziekenhuisgroep, location Den Helder
  • Eindhoven, Netherlands, 5611 NV
    • Andromed Eindhoven
  • Groningen, Netherlands, 9711 SG
    • Andromed Noord
  • Hoorn, Netherlands, 1624 NP
    • Vasculair Onderzoek Centrum
  • Maastricht, Netherlands, 6229 HX
    • Maastricht Universitair Medisch Centrum
  • Rotterdam, Netherlands, 3083 AN
    • Ikazia Ziekenhuis
  • Rotterdam, Netherlands, 3039 BD
    • Andromed Rotterdam
  • Rotterdam, Netherlands, 3039 BD
    • Rotterdam Research Institute
  • Sneek, Netherlands, 8601 ZK
    • Antonius Ziekenhuis
  • Velp, Netherlands, 6883 ES
    • Andromed Oost
  • Zoetermeer, Netherlands, 2724 EK
    • Andromed Leiden-Zoetermeer
• New Zealand
  • Christchurch, New Zealand, 4710
    • Christchurch Hospital
  • Dunedin, New Zealand, 9012
    • RMC Medical Research Ltd
  • Newtown Wellington NZ, New Zealand, 6021
    • P3 Research, Wellington
  • Tauranga, New Zealand, 3110
    • P3 Research, Promed House
• Norway
  • Bodø, Norway, N-8001
    • Bodø Legesenter AS, avd. for med. studier
  • Elverum, Norway, N-2408
    • Medi 3 Innlandet AS, avd Elverum
  • Gjettum, Norway, N-1346
    • Vestre Viken HF, Bærum Sykehus
  • Hamar, Norway, N-2317
    • M3 Helse AS
  • Jessheim, Norway, N-2050
    • Bylegene SA
  • Lierskogen, Norway, N-3420
    • Heiaklinikken
  • Oslo, Norway, N-0160
    • Radhuset Spesialistsenter
  • Sandvika, Norway, N-1337
    • Sandvika Spesialistsenter
  • Sarpsborg, Norway, N-1727
    • Grålum legesenter
  • Stavanger, Norway, N-4005
    • Forusakutten - Kolibri Medical, Avd. Stavanger
  • Ålesund, Norway, N-6002
    • Medi 3 AS
• Peru
  • Arequipa, Peru, LIMA 54
    • Instituto Delgado de Investigacion Medica
  • Huacho, Peru
    • Clinica San Pedro
  • Lima, Peru, Lima 32
    • Clinica San Gabriel
  • Lima, Peru, Lima 1
    • Clinica Internacional
  • Lima, Peru, 01
    • Hospital Nacional Dos de Mayo
  • Lima, Peru, Lima 27
    • Centro de Investigaciones Médicas METABOLICARE SAC
  • Piura, Peru
    • Centro De Especialidades Medicas Santa Maria S.A.C
  • San Miguel, Peru, 32
    • Clinica San Judas Tadeo
• Philippines
  • Iloilo, Philippines, 5000
    • Center for Diabetes Care
  • Lipa City, Batangas, Philippines, 4217
    • Mary Mediatrix Medical Center
  • Manila, Philippines, 1000
    • Philippine General Hospital
  • Manila, Philippines, 1008
    • University of Santo Tomas Hospital
  • Manila, Philippines, 1011
    • Manila Doctors Hospital
  • Muntinlupa, Philippines, 1781
    • Asian Hospital & Medical Center
  • Quezon City, Philippines, 1109
    • Quirino Memorial Medical Center
  • Quezon City, Philippines, 1102
    • St. Luke's Medical Center
  • San Juan, Philippines, 1503
    • Cardinal Santos Medical Center
  • Surigao, Philippines, 8400
    • Surigao Health Specialists
• Portugal
  • Amadora, Portugal, 2700-276
    • Hospital Fernando Fonseca, EPE
  • Carnaxide, Portugal, 2799-523
    • CHLO, EPE - Hospital de Santa Cruz
  • Coimbra, Portugal, 3000-075
    • CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
  • Covilhã, Portugal, 6200-251
    • Centro Hospitalar da Cova da Beira Hospital Pêro da Covilhã
  • Figueira da Foz, Portugal, 3094-001
    • Hospital Distrital Figueira da Foz, EPE
  • Lisboa, Portugal, 1500-650
    • Hospital da Luz
  • Porto, Portugal, 4202-451
    • Centro Hospitalar São João,EPE
  • Santa Maria da Feira, Portugal, 4520-211
    • Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião
• Romania
  • Brasov, Romania, 500365
    • SC Diabol SRL, Brasov
  • Bucharest, Romania, 010507
    • Nicodiab SRL, Bucharest
  • Bucharest, Romania, 020614
    • SC Medical Centre "Sanatatea Ta" SRL, Bucharest
  • Iasi, Romania, 700547
    • Consultmed SRL, Iasi
  • Sibiu, Romania, 550245
    • Emergency County Clinical Hospital, Sibiu
  • Tirgoviste, Romania, 130083
    • Private Practice Dr. Remus Gagiu
• Russian Federation
  • Dzerzhinsky, Russian Federation, 140091
    • LLC Clinic of new technologies of medicine
  • Izhevsk, Russian Federation, 436000
    • City Clinical Hospital No. 6 of MoH of Udmurt Republic
  • Moscow, Russian Federation, 115093
    • City Clinical Hospital No. 4, Moscow
  • Moscow, Russian Federation, 115280
    • City Clinical Hospital No. 13, Moscow
  • Moscow, Russian Federation, 117333
    • State Institution "Central Clinical Hospital of RAS", Moscow
  • Moscow, Russian Federation, 119048
    • City Clinical Hospital No. 61, Moscow
  • Rostov-na-Donu, Russian Federation, 344029
    • State Healthcare Institution, Regional hospital #2
  • Samara, Russian Federation, 443067
    • Limited Liability Company "CENTER DIABET", Samara
  • Saratov, Russian Federation, 410018
    • MMU City Outpatient Clinic no. 20, Saratov
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Medical Center Zvezdara, Belgrade
  • Nis, Serbia, 18000
    • Clinical Centre Nis
  • Pancevo, Serbia, 26000
    • General Hospital Pancevo
  • Subotica, Serbia, 24000
    • General Hospital Subotica, Internal Medicine
  • Zemun, Serbia, 11080
    • Clinical Hospital Center Zemun
• Slovakia
  • Banska Bystrica, Slovakia, 974 01
    • DIASTYLE s.r.o., Diabetology Outpatient Department
  • Dolny Kubin, Slovakia, 026 01
    • ENDIAMED s.r.o., Dolny Kubin
  • Levice, Slovakia, 934 01
    • CELL B s.r.o.
  • Levice, Slovakia, 934 01
    • DIA-KONTROL s.r.o.
  • Nove Zamky, Slovakia, 940 01
    • Funkystuff s.r.o., Nove Zamky
  • Povazska Bystrica, Slovakia, 017 01
    • Diabetologicka ambulancia MUDr. Lucia Gajdosikova s.r.o.
  • Zilina, Slovakia, 010 01
    • MEDIVASA s.r.o., Outpatient Clinic, Zilina
• South Africa
  • Cape Town, South Africa, 7764
    • Dr. P. Patel
  • Cape Town, South Africa, 7965
    • Dr. E. L. Janari
  • Durban, South Africa, 4091
    • Parklands Medical Centre
  • Durban, South Africa, 4091
    • Dr. Vawda
  • Krugersdorp, South Africa, 1739
    • Dr. Jurgens
  • Lenasia, South Africa, 1827
    • Dr. H. Makan
  • Lenasia, South Africa, 2033
    • Dr. D. R. Lakha, Johannesburg
  • Port Elizabeth, South Africa, 6045
    • Greenacres Hospital
  • Pretoria, South Africa, 0083
    • Dr. M. Seeber
  • Somerset West, South Africa, 7130
    • Vergelegen Medi-Clinic
• Spain
  • Barcelona, Spain, 08025
    • C.A.P. Sardenya
  • Barcelona, Spain, 08028
    • CAP Les Corts
  • Barcelona, Spain, 08036
    • CAP Casanova
  • Burjassot, Spain, 46100
    • CAP Burjassot 1
  • Gijon, Spain, 33212
    • C.S. Natahoyo
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Doctor Josep Trueta
  • L'Hospitalet de Llobregat, Spain, 08907
    • Hospital de Bellvitge
  • L'Hospitalet de Llobregat, Spain, 08905
    • CAP Florida
  • La Roca Del Vallés (Barcelona), Spain, 08430
    • CAP La Roca
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Oviedo, Spain, 33006
    • C.S. El Cristo
  • Oviedo, Spain, 33010
    • C.S. Colloto
  • Oviedo, Spain, 33012
    • C.S. Vallobin-La Florida
  • Pineda de Mar, Spain, 08397
    • ABS Pineda de Mar
  • Santa Coloma De Gramanet, Spain, 08923
    • Hospital de l'Esperit Sant
  • Tàrrega, Spain, 25300
    • CAP Tàrrega
  • Valencia, Spain, 46010
    • Hospital Clinico de Valencia
  • Valencia, Spain, 46006
    • CS Ingeniero Joaquin Benlloch
• Sweden
  • Göteborg, Sweden, 413 45
    • CTC Sahlgrenska Universitetssjukhuset
  • Härnösand, Sweden, 87182
    • Sjukhuset, Härnösand
  • Järfälla, Sweden, 177 30
    • Avonova Hälsa AB
  • Malmö, Sweden, 20502
    • Skånes Universitetssjukhus, Malmo
  • Rättvik, Sweden, 795 30
    • Dalecarlia Clinical Research Center
  • Rättvik, Sweden, 79530
    • Södra Dalarnas vårdcentral, Hedemora
  • Skanör, Sweden, 239 33
    • Näsets Läkargrupp
  • Uddevalla, Sweden, 451 50
    • Vårdcentralen Silentzvägen
  • Vällingby, Sweden, 162 68
    • S3 Clinical Research Centers
• Switzerland
  • Basel, Switzerland, 4057
    • Allgemeine Medizin
  • Bellinzona, Switzerland, 6500
    • FMH endocrinologia diabetologia
  • Bern, Switzerland, 3010
    • Inselspital Bern
  • Lugano, Switzerland, 6900
    • Dr. Pietro Gerber
• Taiwan
  • Changhua, Taiwan, 500
    • Chang-Hua Christian Hospital
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung, Taiwan, 824
    • E-Da Hospital
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taichung,, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • NCKUH
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taipei, Taiwan, 114
    • Tri-Service General Hospital
  • Taipei, Taiwan, 112
    • Cheng Hsin General Hospital
  • Taipei, Taiwan, 25160
    • Mackay Memorial Hospital
  • Taipei, Taiwan, 11217
    • Taipe Veterans General Hospital
  • Taipei, Taiwan, 111
    • Shih-Kong Wu Ho-Shu Memorial Hospital
  • Taipei, Taiwan, 23137
    • Cardinal Tien Hospital
  • Taipei, Taiwan, 235
    • Taipei Medical University-Shuang Ho Hospital
• Tunisia
  • Monastir, Tunisia, 5000
    • HOP Fattouma Bourguiba, Mint, Monastir
  • Sfax, Tunisia, 3029
    • HOP Hédi Chaker, Endo, Sfax
  • Sousse, Tunisia, 4000
    • HOP Farhat Hached, Mint, Sousse
  • Tunis, Tunisia, 1008
    • HOP Habib Thameur, Mint, Tunis
• Ukraine
  • Donetsk, Ukraine, 83003
    • Donetsk Regional Clinical Hosp, Therapy Department
  • Ivano-Frankivsk, Ukraine, 76000
    • Ivano-Frankivsk City Central Clinical Hospital
  • Kharkiv, Ukraine, 61037
    • City Clinical Hospital No. 17, Kharkov
  • Kharkov, Ukraine, 61002
    • City Clinical Hospital No. 27, Kharkiv
  • Kiev, Ukraine, 01032
    • Clinic for Cardiology "Sertse i sudyny", Kiev
  • Kiev, Ukraine, 02091
    • City Clinical Hospital No. 1, Kiev
  • Kyiv, Ukraine, 02002
    • Poliklinika #2, Kyiv
  • Lvov, Ukraine, 73013
    • City Hospital No. 5, Lvov
  • Odesa, Ukraine, 65039
    • Odeska zaliznichna likarnya, Odessa
  • Vinnitsa, Ukraine, 21010
    • Vinnitsia Regional Endocrinology Dispensary
• United Kingdom
  • Addlestone, United Kingdom, KT15 2BH
    • Crouch Oak Family Practice
  • Ash Vale, Aldershot, United Kingdom, GU12 5BA
    • Ash Vale Health Centre, Aldershot
  • Birmingham, United Kingdom, B9 5SS
    • Birmingham Heartlands Hospital
  • Chippenham, United Kingdom, SN14 6GT
    • Hathaway Medical Centre
  • Durham, United Kingdom, DH1 5TW
    • University Hospital of North Durham
  • Ely, United Kingdom, CB7 4HF
    • St Mary's Surgery
  • Gloucester, United Kingdom, GL1 3NN
    • Gloucestershire Royal Hospital
  • Great Yarmouth, United Kingdom, NR31 6LA
    • James Paget University Hospital
  • Swansea, United Kingdom, SA6 6NL
    • Morriston Hospital
  • Truro, United Kingdom, TR1 3LJ
    • Royal Cornwall Hospital
• United States
  • Alabama
    • Athens, Alabama, United States, 35611
      • North Alabama Research Center, LLC
    • Birmingham, Alabama, United States, 35235
      • Alabama Internal Medicine, PC
    • Birmingham, Alabama, United States, 35242
      • Cahaba Research, Inc.
    • Mobile, Alabama, United States, 36608
      • Internal Medicine Center, LLC
    • Mobile, Alabama, United States, 36695
      • Diagnostic and Medical Clinic
    • Montgomery, Alabama, United States, 36106
      • Extended Arm Physicians, Inc.
    • Tuscumbia, Alabama, United States, 35674
      • Office of Dr. Terence T. Hart MD
  • Alaska
    • Pell City, Alaska, United States, 35128
      • Advanced Clinical Research
  • Arizona
    • Mesa, Arizona, United States, 85203
      • Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC
    • Mesa, Arizona, United States, 85213
      • Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC
    • Tucson, Arizona, United States, 85712
      • Quality of Life Medical & Research Center
    • Tucson, Arizona, United States, 85704
      • Genova Clinical Research
  • Arkansas
    • Jonesboro, Arkansas, United States, 72404
      • Northeast Arkansas Baptist Clinic
    • Little Rock, Arkansas, United States, 72205
      • Medical Investigations, Inc
    • Little Rock, Arkansas, United States, 72211
      • Aureus Research, Inc
  • California
    • Bermuda Dunes, California, United States, 92203
      • Desert Oasis Healthcare
    • Fountain Valley, California, United States, 92708
      • Edinger Medical Group and Research Center
    • Fullerton, California, United States, 92835
      • Clinical Trials of St. Jude Heritage Med. Group
    • Long Beach, California, United States, 90807
      • Long Beach Center For Clinical Research
    • Los Gatos, California, United States, 95032
      • Office of Dr. Richard S. Cherlin
    • North Hollywood, California, United States, 91606
      • Providence Clinical Research
    • Pomona, California, United States, 91767
      • Chaparral Medical Group, Inc
    • Redondo Beach, California, United States, 90277
      • ARI Clinical Trials, Inc
    • San Diego, California, United States, 92120
      • San Diego Sports Medicine and Family Health Center
    • San Ramon, California, United States, 94582
      • West Coast Research, LLC
    • Sylmar, California, United States, 91342
      • University of California Los Angeles
    • Tarzana, California, United States, 91356
      • Metabolic Institute of America
    • Tustin, California, United States, 92780
      • Orange County Research Center
    • Tustin, California, United States, 92780
      • Matrix Research Institute
    • Westlake Village, California, United States, 91361
      • Westlake Medical Research
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC
    • Colorado Springs, Colorado, United States, 80920
      • Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC
  • Florida
    • Boca Raton, Florida, United States, 33433
      • East Coast Medical Associates
    • Davie, Florida, United States, 33314
      • Todd Kazdan, DO Family Practice
    • Daytona Beach, Florida, United States, 32117
      • Century Clinical Research, Inc
    • Doral, Florida, United States, 33172
      • Doral Research Center
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research
    • Fort Lauderdale, Florida, United States, 33316
      • M & O Clinical Research, LLC
    • Fort Lauderdale, Florida, United States, 33309
      • Alan Graff, MD, PA
    • Hialeah, Florida, United States, 33013
      • Eastern Research
    • Hialeah, Florida, United States, 33013
      • Research in Miami Inc
    • Jacksonville, Florida, United States, 32223
      • Jacksonville Impotence Treatment Center
    • Jacksonville, Florida, United States, 32258
      • East Coast Institute for Research, LLC
    • Jacksonville, Florida, United States, 32277
      • Care Partners Clinical Research LLC
    • Lauderdale Lakes, Florida, United States, 33319
      • Precision Clinical Research, LLC
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33155
      • AppleMed Research Group, LLC
    • Miami, Florida, United States, 33147
      • Advanced Pharma Cr, Llc
    • Miami, Florida, United States, 33143
      • Well Pharma Medical Research
    • Miami, Florida, United States, 33134
      • APF Research, LLC
    • Miami, Florida, United States, 33185
      • Kendall South Medical Center, Inc
    • Miami, Florida, United States, 33126
      • Veritas Research Corporation
    • Miami, Florida, United States, 33135
      • Swiss Medical Research
    • Miami, Florida, United States, 33143
      • South Miami Clinical Research
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute, Inc
    • Opa-locka, Florida, United States, 33054
      • Sunshine Research Center
    • Orlando, Florida, United States, 32803
      • Diabetes and Endocrine Center of Orlando
    • Palm Harbor, Florida, United States, 34684
      • Suncoast Clinical Research
    • Panama City, Florida, United States, 32401
      • Misal Khan, MD FRCS, ED, PA
    • Pembroke Pines, Florida, United States, 33024
      • Iconic Clinical Trials
    • Pensacola, Florida, United States, 32514
      • Gulf Region Clinical Research Institute
    • Ponte Vedra Beach, Florida, United States, 32081
      • St. John's Center for Clinical Research
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates
    • Atlanta, Georgia, United States, 30312
      • PMI Health Research Group
    • Dunwoody, Georgia, United States, 30338
      • Albert F. Johary MD, PC
    • Snellville, Georgia, United States, 30078
      • Georgia Clinical Research, LLC
  • Idaho
    • Hayden Lake, Idaho, United States, 83835
      • Hayden Lake Family Physicians
    • Meridian, Idaho, United States, 83642
      • Boise Kidney and Hypertension Institute
  • Illinois
    • Bolingbrook, Illinois, United States, 60490
      • Suburban Clinical Research
    • Chicago, Illinois, United States, 60616
      • Apex Medical Research
    • Chicago, Illinois, United States, 60607
      • Cedar-Crosse Research Center
    • Chicago, Illinois, United States, 60612
      • John H. Stroger Jr. Hospital of Cook Country
    • Evergreen Park, Illinois, United States, 60805
      • Pharmakon Inc
  • Indiana
    • Avon, Indiana, United States, 46123
      • American Health Network
    • Brownsburg, Indiana, United States, 46112
      • Investigators Research Group, LLC
    • Franklin, Indiana, United States, 46131
      • American Health Network of Indiana, LLC
    • Indianapolis, Indiana, United States, 46205
      • Mapleton Medical Center
    • Indianapolis, Indiana, United States, 46254
      • American Health Network, LLC
    • Mishawaka, Indiana, United States, 46545
      • McKinley Research, LLC
    • Muncie, Indiana, United States, 47304
      • American Health Network of Indiana, LLC
  • Kentucky
    • Florence, Kentucky, United States, 41042
      • MCM Clinical Research, LLC
    • Lexington, Kentucky, United States, 40503
      • Kentucky Diabetes Endocrinology Center
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Inc
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Crescent City Clinical Research
  • Maine
    • Bangor, Maine, United States, 04401
      • Acadia Clinical Research, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21234
      • Office of Dr. Stephen R. Smith, MD
    • Rockville, Maryland, United States, 20852
      • Endocrine and Metabolic Consultants
  • Massachusetts
    • North Attleboro, Massachusetts, United States, 02760
      • Tristan Medical Enterprises, PC dba Regeneris
  • Michigan
    • Canton, Michigan, United States, 48187
      • ClinSite, LLC
    • Flint, Michigan, United States, 48504
      • Apex Medical Research, AMR Inc
    • Kalamazoo, Michigan, United States, 49009
      • Westside Family Medical Center, Pc
    • Livonia, Michigan, United States, 48152
      • Tri City Medical Centers, PC
    • Saint Clair Shores, Michigan, United States, 48081
      • KMED Research
    • Sterling Heights, Michigan, United States, 48310
      • Tri-County Research, Inc
    • Traverse City, Michigan, United States, 49684
      • Medical Research Associates
    • Troy, Michigan, United States, 48085
      • Oakland Medical Research Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Park Nicollet Institute
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • The Center for Clinical Trials, Inc.
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC
    • Las Vegas, Nevada, United States, 89121
      • Clinical Research of South Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Medical Research Center
  • New Jersey
    • Atco, New Jersey, United States, 08004
      • Atco Medical Associates, PC
    • Clifton, New Jersey, United States, 07012
      • Summit Medical Group
    • Elizabeth, New Jersey, United States, 07201
      • USMA Clinical Research
    • Elizabeth, New Jersey, United States, 07202
      • Central Jersey Medical Research
  • New York
    • Albany, New York, United States, 12206
      • Albany Medical Center / Albany Medical College
    • Smithtown, New York, United States, 11787
      • Endocrine Associates of Long Island, PC
    • West Seneca, New York, United States, 14224
      • Southgate Medical Group/ Southgate Medical Park
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • OnSite Clinical Solutions, LLC
    • Burlington, North Carolina, United States, 27215
      • Kernodle Clinic West
    • Chapel Hill, North Carolina, United States, 27517
      • The University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28205
      • Gaffney Health Services
    • Charlotte, North Carolina, United States, 28204
      • Internal Medicine Research
    • Durham, North Carolina, United States, 27704
      • Durham Internal Medicine Associates
    • Elizabeth City, North Carolina, United States, 27909
      • Sentara Family Medicine
    • Raleigh, North Carolina, United States, 27609
      • PMG Research of Raleigh, LLC
    • Shelby, North Carolina, United States, 28150
      • Carolina Research Center, Inc
    • Statesville, North Carolina, United States, 28625
      • Piedmont Healthcare
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
  • Ohio
    • Akron, Ohio, United States, 44319
      • Community Health Care Of Manchester
    • Austintown, Ohio, United States, 44515
      • Community Medical Associates, LLC
    • Cadiz, Ohio, United States, 43907
      • Harrison Community Research Center
    • Carlisle, Ohio, United States, 45005
      • Medical Frontiers, LLC
    • Genoa, Ohio, United States, 43430
      • Genoa Medical Center
    • Marion, Ohio, United States, 43302
      • Office of Dr. Craig S. Thompson, MD, LLC
    • Marion, Ohio, United States, 43302
      • RAS Health Limited
    • Maumee, Ohio, United States, 43537
      • Advanced Medical Research, LLC
    • Zanesville, Ohio, United States, 43701
      • Pharmacotherapy Research Associates, Inc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Infinity Research Group, LLC
    • Tulsa, Oklahoma, United States, 74136
      • Castlerock Clinical Research Consultants, Llc
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oregon Medical Group
  • Pennsylvania
    • Harleysville, Pennsylvania, United States, 19438
      • Harleysville Medical Associates
    • Lansdale, Pennsylvania, United States, 19446
      • Detweiler Family Medicine & Associates, PC
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University School of Medicine
    • Warminster, Pennsylvania, United States, 18974
      • Warminster Medical Associates, PC
  • Rhode Island
    • Cranston, Rhode Island, United States, 02920
      • New England Center for Clinical Research, Inc
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Hartwell Research Group, LLC
    • Greenville, South Carolina, United States, 29601
      • Paris View Family Practice
    • Greer, South Carolina, United States, 29651
      • Mountain View Clinical Research
    • Orangeburg, South Carolina, United States, 29118
      • South Carolina Nephrology and Hypertension Center, Inc
    • Sumter, South Carolina, United States, 29150
      • Carolina Diabetes & Kidney Center
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • PMG Research of Bristol
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes and Endocrine Consultants
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee
    • Tullahoma, Tennessee, United States, 37388
      • Trinity Clinical Research, LLC
  • Texas
    • Arlington, Texas, United States, 76012
      • KRK Medical Research
    • Austin, Texas, United States, 78758
      • Austin Center for Clinical Research
    • Carrollton, Texas, United States, 75006
      • Punzi Medical Center
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes and Endocrine Center
    • Dallas, Texas, United States, 75246
      • Baylor Endocrine Center
    • Dallas, Texas, United States, 75390-8858
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions, Inc.
    • Houston, Texas, United States, 77040
      • JVC Family Medicine
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77030
      • Jacon Medical Research Associates, LLC
    • Houston, Texas, United States, 77095
      • Endocrine and Psychiastry Center
    • Midland, Texas, United States, 79707
      • Midland Clinical Research Center
    • New Braunfels, Texas, United States, 78130
      • Hill Country Medical Associates
    • Odessa, Texas, United States, 79761
      • Naidu Clinic
    • Pearland, Texas, United States, 77584
      • The Methodist Hospital d/b/a HMRI CCAT at Pearland
    • Plano, Texas, United States, 75024
      • Village Health Partners
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
    • Schertz, Texas, United States, 78154
      • Northeast Clinical Research of San Antonio, LLC
    • Sugar Land, Texas, United States, 77478
      • Kenneth Otah and Associates
  • Utah
    • Midvale, Utah, United States, 84047
      • PHS Clinical Trials
    • Salt Lake City, Utah, United States, 84124
      • Highland Clinical Research
  • Virginia
    • Burke, Virginia, United States, 22015
      • Burke Internal Medicine and Research
    • Ettrick, Virginia, United States, 23803
      • Ettrick Health Center
    • Manassas, Virginia, United States, 20110
      • Manassas Clinical Research Center
    • Richmond, Virginia, United States, 23220
      • Clinical Research Partners, LLC
    • Richmond, Virginia, United States, 23220
      • Richmond Family Practice
  • Washington
    • Federal Way, Washington, United States, 98003
      • Larry D Stonesifer, MD Inc., PS
    • Spokane, Washington, United States, 99204
      • Premier Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Type 2 diabetes
2. Elevated glycosylated haemoglobin (HbA1c): 6.5 - 8.5%, inclusive, if treatment naïve or mono-/dual therapy with metformin and/or an alpha-glucosidase inhibitor; 6.5 - 7.5%, inclusive, if treatment with sulphonylurea/glinide in mono- or dual (with metformin OR an alpha-glucosidase inhibitor) therapy)
3. Pre-existing cardiovascular disease OR specified diabetes end-organ damage OR age => 70 years OR two or more specified cardiovascular risk factor
4. BMI =< 45kg/m²
5. age between >= 40 and =< 85 years
6. signed and dated written International Conference of Harmonisation( ICF)
7. stable anti-diabetic background for at least 8 wks before study start

Exclusion criteria:

1. Type 1 diabetes
2. Treatment with other antidiabetic drugs (e.g. rosiglitazone, pioglitazone, Glucagon-like peptide 1 (GLP-1) analogue/agonists, Dipeptidyl-peptidase IV (DPP-IV) inhibitors or any insulin) prior to informed consent (previous short term use of insulin (up to two weeks) is allowed if taken at least 8 weeks prior informed consent)
3. treatment with any anti-obesity drug less than 3 months before ICF
4. uncontrolled hyperglycemia
5. previous or planned bariatric surgery or intervention
6. current or planned system corticoid treatment
7. change in thyroid hormones treatment
8. acute liver disease or impaired hepatic function
9. pre-planned coronary artery revascularization within 6 months of ICF
10. known hypersensitivity to any of the components
11. Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information
12. congestive heart failure class III or IV
13. acute or chronic metabolic acidosis
14. hereditary galactose intolerance
15. alcohol or drug abuse
16. participation in another trail with IMP given 2 months before Investigational Medicinal/Medical Product (IMP) start
17. pre-menopausal women who are nursing or pregnant or of child-bearing potential and not willing to use acceptable method of birth control
18. patients considered reliable by the investigator
19. acute coronary syndrome =< 6 wks before ICF
20. stroke or Transient Ischemic Attack (TIA) =< 3 months prior to ICF

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: linagliptin; patient to receive linagliptin or glimepiride placebo over encapsulated tablet Quaque die (QD)	Drug: linagliptin; linagliptin tablets 5mg QD; Drug: glimepiride placebo; glimepiride placebo
Active Comparator: glimepiride 1-4 mg QD; patient to receive glimepiride 1-4 mg or linagliptin placebo tablet Quaque die (QD)	Drug: glimepiride; glimepiride over-encapsulated tablet 1-4 mg QD; Drug: linagliptin placebo; linagliptin placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The First 3-point Major Adverse Cardiovascular Events (3P-MACE)	The first occurrence of any of the following Clinical Event Committee (CEC) confirmed adjudicated components of the primary composite endpoint: CV death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI (excluding silent MI), or nonfatal stroke is presented.	From randomization until individual day of trial completion, up to 432 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The First 4-point (4P)- MACE	The first key secondary endpoint was time to first occurrence of any of the following adjudicated components of the composite endpoint: CV death (including fatal stroke and fatal MI), non-fatal stroke, non-fatal MI (excluding silent MI), or hospitalisation for unstable angina pectoris.	From randomization until individual day of trial completion, up to 432 weeks
Percentage of Participants Taking Trial Medication at Trial End, Maintained Glycaemic Control (HbA1c ≤7.0%) Without Need for Rescue Medication, Without >2% Weight Gain, and Without Moderate/Severe Hypoglycaemic Episodes During Maintenance Phase	The second key secondary endpoint was a composite endpoint of treatment sustainability, defined as the percentage of patients taking trial medication at trial end, maintained glycaemic control (HbA1c ≤7.0%) without need for rescue medication, without >2% weight gain, and without moderate/severe hypoglycaemic episodes during maintenance phase.	From Visit 6 (Week 16) to Final visit (Week 432) (Maintenance Phase)
Percentage of Participants Who Were on Trial Medication at Trial End, Maintained Glycaemic Control (HbA1c ≤7.0%) Without Need for Rescue Medication, and Without >2% Weight Gain During Maintenance Phase	The third key secondary endpoint was a composite endpoint of treatment sustainability, defined as percentage of patients who were on trial medication at trial end, maintained glycaemic control (HbA1c ≤7.0%) without need for rescue medication, and without >2% weight gain during maintenance phase.	From Visit 6 (Week 16) to Final visit (Week 432) (Maintenance Phase)
Percentage of Participants With the Occurrence of at Least One Event of 3P-MACE	Percentage of participants occurrence of at least one of the following adjudicated components of CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI) and non-fatal stroke is presented as secondary CV endpoint.	From randomization until individual day of trial completion, up to 432 weeks
Percentage of Participants With the Occurrence of at Least One Event of 4P -MACE	Percentage of participants occurrence of at least one of the following adjudicated components of CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI), non-fatal stroke, and hospitalisation for unstable angina pectoris is presented as secondary CV endpoint.	From randomization until individual day of trial completion, up to 432 weeks
Percentage of Participants With Occurrence of Any of the Components of the Composite Endpoint of All Adjudication-confirmed Events	Percentage of participants with occurrence of any of the following components of the composite endpoint of all adjudication-confirmed events of: CV death (including fatal stroke and fatal MI); non-fatal MI; non-fatal stroke; hospitalisation for unstable angina pectoris; TIA; hospitalisation for heart failure; hospitalisation for coronary revascularisation procedures (CABG, PCI)	From start of the treatment until 7 days after the end of treatment, up to 433 weeks
Time to First Occurrence of Any of the Components of the Composite Endpoint of All Adjudication-confirmed Events	Time to first occurrence of any of the following components of the composite endpoint of all adjudication-confirmed events of: CV death (including fatal stroke and fatal MI); non-fatal MI; non-fatal stroke; hospitalisation for unstable angina pectoris; Transient ischaemic attack (TIA); hospitalisation for heart failure; hospitalisation for coronary revascularisation procedures (CABG, PCI)	From start of the treatment until 7 days after the end of treatment, up to 433 weeks
Change From Baseline to Final Visit in Hemoglobin A1c (HbA1c)	Change from baseline to final visit in HbA1c is presented as secondary diabetes-related endpoint. Least square mean is adjusted mean. The Final Visit value referred to the last value obtained on-treatment.	Baseline and week 432
Change From Baseline to Final Visit in Fasting Plasma Glucose (FPG)	Change from baseline to final visit in fasting plasma glucose (FPG) is presented as secondary diabetes-related endpoint. Least square mean is adjusted mean. The Final Visit value referred to the last value obtained on-treatment.	Baseline and week 432
Change From Baseline to Final Visit Fasting Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and High-density Lipoprotein (HDL) Cholesterol	Change from baseline to final visit in total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol is presented as secondary diabetes-related endpoint. Least square mean is adjusted mean. The Final Visit value referred to the last value obtained on-treatment.	Baseline and week 432
Change From Baseline to Final Visit in Triglycerides	Change from baseline to final visit in triglycerides is presented as secondary diabetes-related endpoint. Least square mean is adjusted mean. The Final Visit value referred to the last value obtained on-treatment.	Baseline and week 432
Change From Baseline to Final Visit in Creatinine	Change from baseline to final visit in creatinine is presented as secondary diabetes-related endpoint. Least square mean is adjusted mean. The Final Visit value referred to the last value obtained on-treatment.	Baseline and week 432
Change From Baseline to Final Visit in Estimated Glomerular Filtration Rate (eGFR)	Change from baseline to final visit in eGFR is presented as secondary diabetes-related endpoint. Least square mean is adjusted mean. The Final Visit value referred to the last value obtained on-treatment.	Baseline and week 432
Change From Baseline to Final Visit in Urine Albumin Creatinine Ratio (UACR)	Change from baseline to final visit in UACR is presented as secondary diabetes-related endpoint. Least square mean is adjusted geometric mean (gMean) ratio. The Final Visit value referred to the last value obtained on-treatment.	Baseline and week 432
Percentage of Participants With Transition in Albuminuria Classes	Percentage of patients with transition in albuminuria classes is presented as secondary endpoint. Data for last value on treatment (LVOT) to baseline (base) is presented.	Baseline and week 432
Change From Baseline of Insulin Secretion Rate (ISR) at Fixed Glucose Concentration at 208 Weeks	The endpoint change from baseline of ISR at fixed glucose concentration at 208 weeks as derived from a 3-hour meal tolerance test is Beta-cell function sub-study endpoint.	Baseline and week 208
Percentage of Participants With Occurrence of Accelerated Cognitive Decline at End of Follow-up	Occurrence of accelerated cognitive decline based on regression based index (RBI) score at end of follow-up (a dichotomous outcome measure; presence or absence of accelerated cognitive decline) is Cognition sub-study endpoint.	433 weeks
Continuous Glucose Monitoring (CGM) Sub-study: Change From Baseline in the Inter-quartile Range of Diurnal Glucose Variability (Milligrams/ Deciliter) to End of Study	Baseline data for the continuous glucose monitoring sub-study was collected and analyzed. However, the participant number was far less than original planned. The study was stopped early around week 64 (V9) due to recruitment issues and data were not pre-specified to be analyzed and reported at week 64 time point as target was with an estimated time point of 432 weeks for primary or secondary end points. Thus this endpoint was not analysed and only the baseline data collected were analysed and the results are reported in this CGM substudy endpoint.	Baseline
CGM Sub-study : Change From Baseline in the Inter-quartile Range of Diurnal Glucose Variability (Millimoles/ Litre) to End of Study	Baseline data for the continuous glucose monitoring sub-study was collected and analyzed. However, the participant number was far less than original planned. The study was stopped early around week 64 (V9) due to recruitment issues and data were not pre-specified to be analyzed and reported at week 64 time point as target was with an estimated time point of 432 weeks for primary or secondary end points. Thus this endpoint was not analysed and only the baseline data collected were analysed and the results are reported in this CGM substudy endpoint.	Baseline

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• Verhagen C, Janssen J, Minderhoud CA, van den Berg E, Wanner C, Passera A, Johansen OE, Biessels GJ. Chronic kidney disease and cognitive decline in patients with type 2 diabetes at elevated cardiovascular risk. J Diabetes Complications. 2022 Oct;36(10):108303. doi: 10.1016/j.jdiacomp.2022.108303. Epub 2022 Aug 31.
• Verhagen C, Janssen J, Biessels GJ, Johansen OE, Exalto LG. Females with type 2 diabetes are at higher risk for accelerated cognitive decline than males: CAROLINA-COGNITION study. Nutr Metab Cardiovasc Dis. 2022 Feb;32(2):355-364. doi: 10.1016/j.numecd.2021.10.013. Epub 2021 Oct 27.
• Biessels GJ, Verhagen C, Janssen J, van den Berg E, Wallenstein G, Zinman B, Espeland MA, Johansen OE. Effects of linagliptin vs glimepiride on cognitive performance in type 2 diabetes: results of the randomised double-blind, active-controlled CAROLINA-COGNITION study. Diabetologia. 2021 Jun;64(6):1235-1245. doi: 10.1007/s00125-021-05393-8. Epub 2021 Feb 9.
• Rosenstock J, Kahn SE, Johansen OE, Zinman B, Espeland MA, Woerle HJ, Pfarr E, Keller A, Mattheus M, Baanstra D, Meinicke T, George JT, von Eynatten M, McGuire DK, Marx N; CAROLINA Investigators. Effect of Linagliptin vs Glimepiride on Major Adverse Cardiovascular Outcomes in Patients With Type 2 Diabetes: The CAROLINA Randomized Clinical Trial. JAMA. 2019 Sep 24;322(12):1155-1166. doi: 10.1001/jama.2019.13772. Erratum In: JAMA. 2019 Dec 3;322(21):2138.
• Janssen J, van den Berg E, Zinman B, Espeland MA, Geijselaers SLC, Mattheus M, Johansen OE, Biessels GJ. HbA1c, Insulin Resistance, and beta-Cell Function in Relation to Cognitive Function in Type 2 Diabetes: The CAROLINA Cognition Substudy. Diabetes Care. 2019 Jan;42(1):e1-e3. doi: 10.2337/DC18-0914. No abstract available.
• Biessels GJ, Janssen J, van den Berg E, Zinman B, Espeland MA, Mattheus M, Johansen OE; CAROLINA(R) investigators. Rationale and design of the CAROLINA(R) - cognition substudy: a randomised controlled trial on cognitive outcomes of linagliptin versus glimepiride in patients with type 2 diabetes mellitus. BMC Neurol. 2018 Jan 15;18(1):7. doi: 10.1186/s12883-018-1014-7.
• Marx N, Rosenstock J, Kahn SE, Zinman B, Kastelein JJ, Lachin JM, Espeland MA, Bluhmki E, Mattheus M, Ryckaert B, Patel S, Johansen OE, Woerle HJ. Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA(R)). Diab Vasc Dis Res. 2015 May;12(3):164-74. doi: 10.1177/1479164115570301. Epub 2015 Mar 15.
• Chilton R. Linagliptin versus glimepiride add-on for the long-term treatment of Type 2 diabetes mellitus. Expert Rev Endocrinol Metab. 2013 Jul;8(4):345-349. doi: 10.1586/17446651.2013.811849.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2010
• Primary Completion (Actual): August 21, 2018
• Study Completion (Actual): August 21, 2018

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 17, 2010
• First Posted (Estimate): November 18, 2010

Study Record Updates

• Last Update Posted (Actual): January 7, 2020
• Last Update Submitted That Met QC Criteria: December 19, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin; Glimepiride
• Other Study ID Numbers: 1218.74; 2009-013157-15 (EudraCT Number)