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

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01243424
• Other study ID #: 1218.74
• Secondary ID: 2009-013157-15
• Status: Completed
• Phase: Phase 3
• Start date: November 11, 2010
• Est. completion date: August 21, 2018

Study information

• Verified date: December 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6103
• Est. completion date: August 21, 2018
• Est. primary completion date: August 21, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• linagliptin
linagliptin tablets 5mg QD
• glimepiride
glimepiride over-encapsulated tablet 1-4 mg QD
• linagliptin placebo
linagliptin placebo
• glimepiride placebo
glimepiride placebo

Locations

Country	Name	City	State
Argentina	Instituto de Investigaciones Clínicas de Bahía Blanca	Bahía Blanca
Argentina	CENUDIAB	Caba
Argentina	CIPREC	Caba
Argentina	Consultorios Asociados de Endocrinología e Invest Clínica	Capital Federal
Argentina	Instituto Médico Especializado	Capital Federal
Argentina	IPAC - Clínica Privada Caraffa SRL	Cordoba
Argentina	Ilaim-Ceom	Córdoba
Argentina	Instituto Cardiovascular de Corrientes Juana Francisca Cabra	Corrientes
Argentina	Hospital Italiano de La Plata	La Plata
Argentina	CIPADI	Mendoza
Argentina	Instituto de Hematología y Medicina Clínica Dr. Rubén Davoli	Rosario
Argentina	Instituto de Investigaciones Clinicas de Rosario	Rosario
Argentina	Hospital San Bernardo	Salta
Argentina	Investigaciones Clinicas Tucuman	San Miguel de Tucumán
Argentina	Centro de Investigaciones Clínicas del Litoral	Santa Fe
Argentina	Instituto de Investigaciones Biomédicas	Santa Fe
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Eastern Clinical Research Unit	East Ringwood	Victoria
Australia	Royal Brisbane & Women's Hospital-Endocrinology	Herston	Queensland
Australia	Logan Hospital	Meadowbrook	Queensland
Australia	Royal Melbourne Hospital	Parkville	Victoria
Belgium	Blankenberge - PRAC Vileyn, Geert	Blankenberge
Belgium	Bonheiden - HOSP Imelda	Bonheiden
Belgium	De Pinte - PRAC Hollanders, Geert	De Pinte
Belgium	Retie - PRAC De Vos, Axel	Dessel
Belgium	Deurne - PRAC Heyvaert, Frank	Deurne
Belgium	Deurne - PRAC Verelst, Joost	Deurne
Belgium	Genk - PRAC Vernijns, J.	Genk
Belgium	Gozée - PRAC De Meulemeester, Marc	Gozée
Belgium	Hasselt - PRAC Vantroyen, Daniel	Hasselt
Belgium	Herent - PRAC Denolf, Bart	Herent
Belgium	Linkebeek - PRAC Maury, Olivier	Linkebeek
Belgium	Moorsel - PRAC Van Mulders, N.	Moorsel
Belgium	Natoye - PRAC Balthazar, Y.	Natoye
Belgium	Tremelo - PRAC Vermeersch, Lode	Tremelo
Brazil	Hospital Universitário João de Barros Barreto	Belém
Brazil	Universidade Federal do Paraná	Curitiba
Brazil	Hospital Geral de Goiânia Alberto Rassi	Goiânia
Brazil	Centro de Pesquisas Clínicas Ltda	Higienópolis
Brazil	Centro de Estudos em Diabetes e Hipertensão	Joaquim Távora
Brazil	Centro de Pesquisas em Diabetes	Porto Alegre
Brazil	Irmandade Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Instituto Estadual de Diabetes e Endocrinologia	Río de Janeiro
Brazil	Irmandade da Santa Casa de Misericórdia de São Paulo - IPEC - Instituto de Pesquisa Clínica	Santa Cecília
Brazil	Instituto de Molestias Cardiovasculares - IMC	São José do Rio Preto
Brazil	Hospital das Clinicas da FMUSP	São Paulo
Brazil	Hospital do Rim e Hipertensão - UNIFESP	Vila Clementino
Bulgaria	Univ.Multiprofile Hospital "Dr. Georgy Stranski" EAD, Pleven	Pleven
Bulgaria	Military Medical Academy, Clin. Endocrinology & Metab. Dis.	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment	Sofia
Bulgaria	Multiprofile Hospital for Active Treatment "Zaritza Johanna"	Sofia
Bulgaria	MHAT Prof Stoyan Kirkovich AD	Stara Zagora
Canada	Cambridge Cardiac Care Inc.	Cambridge	Ontario
Canada	Hamilton Medical Research Group	Hamilton	Ontario
Canada	Kings County Medical Centre	Montague	Prince Edward Island
Canada	SKDS Research Incorporated	Newmarket	Ontario
Canada	Dynamik Research	Pointe Claire	Quebec
Canada	IUCPQ (Laval University)	Quebec	Migration Data
Canada	First Line Medical Services Ltd.	St. John's	Newfoundland and Labrador
Canada	Topsail Road Medical Clinic	St. John's	Newfoundland and Labrador
Canada	Wilderman Medical Clinic	Thornhill	Ontario
Canada	Albion Finch Medical Centre	Toronto	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Chile	Consulta Privada Maria Loreto Aguirre Coveña	Providencia
Chile	Hospital de Servicios Médicos Godoy Ltda	Providencia
Chile	Centro Medico Antulawen	Temuco
Chile	Hospital Naval Almirante Nef	Viña del Mar
Colombia	BioMelab	Barranquilla
Colombia	Centro Cientifico Asistencial Jose Luis Accini	Barranquilla
Colombia	Fundacion del Caribe de Investigacion Biomedica	Barranquilla
Colombia	Endocare Research Institute	Bogota
Colombia	Dexa Diabetes Servicios Médicos Ltda	Bogotá
Colombia	UNIENDO Unidad Integral de Endocrinologia	Bogotá
Colombia	Centro cardiovascular Aristides	Cartagena
Colombia	centro de Diagnostico Cardiologico para la Investigacion Bio	Cartagena
Colombia	Fundacion Cardiovascular de Colombia	El Bosque
Colombia	Fundación Oftalmologica de Santander	El Bosque
Colombia	Fundación Centro de Investigaciones Biomédicas Riescard	Tolima
Czechia	Internal & Diabetology Ambulance, Jablonec nad Nisou	Jablonec nad Nisou
Czechia	Diabetology & Internal Ambulance	Olomouc-Lazce
Czechia	Internal & Diabetology Ambulance Dr. Vrkoc, Ostrava	Ostrava
Czechia	Cardiology ambulance, Plzen	Plzen
Czechia	Diebetology internal Ambulance	Praha
Czechia	ResTrial s.r.o.	Praha 8
Czechia	Internal & Diabetology Ambulance, Prostejov	Prostejov
Czechia	Hospital Strakonice, Internal Department	Strakonice
Finland	Diabetesklinikka, Mehiläinen Töölö	Helsinki
Finland	Lääkärikeskus Ite	Joensuu
Finland	Lääkärikeskus Aava Kerava	Kerava
Finland	Kokkolan Lääkärikeskus	Kokkola
Finland	IteLasaretti	Kuopio
Finland	Terveystalo Oulu, Diapolis	Oulu
Finland	TYKS	Turku
France	CAB Hell M, MG, Behren Les Forbach	Behren Les Forbach
France	CAB Breton Dr Nicolas	Béziers
France	HOP Haut Levèque, Diabéto, Pessac	Bordeaux
France	CAB Lemarie B, MG, Bourg des Cptes	Bourg des Comptes
France	CAB Cadinot Dr D, Broglie	Broglie
France	CAB Ferrier R, MG, Cannes	Cannes
France	CAB Jordan E, MG, Carbonne	Carbonne
France	CAB Merlin P, MG Castets	Castets
France	CAB Fonteny R, MG, Chartres	Chartres
France	CAB Fournier P, MG, Chartres	Chartres
France	CAB Martocq G, MG, Cournonterral	Cournonterral
France	HOP, Fort de France, Fort de France	Fort De France
France	CAB Le Mouel S, MG, Hinx	Hinx
France	CAB Pholsena, MG, La Réunion	La Reunion
France	CAB Bismuth M	Labarthe sur Leze
France	CAB Zimmermann D	Louvigne De Bie
France	CAB Mainetti P, MG, Maintenon	Maintenon
France	CAB Barucq F, MG, Orthez	Orthez
France	CAB Mostephai M	Orthez
France	CAB Cassagnes JL, MG, Palau Del Vidre	Palau Del Vidre
France	CAB Mercey Y, MG, St Genies des Fontaines	Saint Genies Des Fontaines
France	Hop St Dié des Vosges, Diabéto, St Dié des Vosges	St Dié des Vosges Cedex
France	CAB Bonneau D, MG, Thouars	Thouars
France	CAB Morel H, MG, Tilly sur Seulles	Tilly sur Seulles
Georgia	Unimed Ajara LLC, Private Practice	Batumi
Georgia	Central Hospital LTD 'Gormedi', Gori	Gori
Georgia	L&J Clinic, Kutaisi	Kutaisi
Georgia	Chemotherapy & Immunotherapy Clinic 'Medulla', Tbilisi	Tbilisi
Georgia	EC Cardiology Clinic,Tbilisi	Tbilisi
Georgia	Medical Centre Medelite Ltd., Tbilisi	Tbilisi
Georgia	National Center for Diabetes Research Ltd., Tbilisi	Tbilisi
Georgia	National Institute of Endocrinology, Tbilisi	Tbilisi
Georgia	Zhordania Institute of Human Reproduction, Tbilisi	Tbilisi
Georgia	JSC 'Curatio'	Zugdidi
Germany	Universitätsklinikum Aachen, AöR	Aachen
Germany	Studienzentrum Klausmann	Aschaffenburg
Germany	Gemeinschaftspraxis, Asslar	Asslar
Germany	Diabetes Schwerpunktpraxis	Bad Nauheim
Germany	emovis GmbH	Berlin
Germany	IFG Institut für Gesundheitsförderung GmbH	Berlin
Germany	Praxis Dr. Naumburger, Berlin	Berlin
Germany	Praxis Dr. Rieker, Berlin	Berlin
Germany	MVZ DaVita Dormagen GmbH	Dormagen- Hackenbroich
Germany	Praxis Dr. Busch, Dortmund	Dortmund
Germany	GWT-TUD GmbH	Dresden
Germany	Praxis Dr. Schlecht, Eisenach	Eisenach
Germany	ZKS Südbrandenburg GmbH	Elsterwerda
Germany	Praxis Dr. Huptas, Essen	Essen
Germany	Praxis Dr. Schmidt, Flörsheim	Flörsheim
Germany	Institut für Stoffwechselforschung, Frankfurt	Frankfurt
Germany	Praxis Dr. Groeneveld, Furth im Wald	Furth im Wald
Germany	Praxis Dr. Kohlhas, Gebhardshain	Gebhardshain
Germany	Praxis Dr. Samer, Haag	Haag
Germany	Diabeteszentrum Alstertal, Hamburg	Hamburg
Germany	Diabetologische Schwerpunktpraxis	Hamburg
Germany	Klinische Forschung Management & Services GmbH	Hamburg
Germany	Praxis Dr. Burkhardt, Hamburg	Hamburg
Germany	Praxis Dr. Herrmann, Hatten	Kirchhatten
Germany	Dünnwaldpraxis, Köln	Köln
Germany	Praxis Dr. Klein, Künzing	Künzing
Germany	Praxis Dr. Nischik, Leipzig	Leipzig
Germany	Praxis Dr. Kropp, Lübeck	Lübeck
Germany	PFÜTZNER Science & Health Institute GmbH	Mainz
Germany	Diabetologische Schwerpunktpraxis	Münster
Germany	Praxis Dr. Böckmann	Neumünster
Germany	Praxis Dr. Hilgenberg	Rehburg-Loccum
Germany	Praxis Dr. Naudts, Rodgau	Rodgau/Dudenhofen
Germany	Praxis Dr. Hirschhäuser	Saarbrücken
Germany	Praxis Dr. Segner, St. Ingberg	Saint Ingbert / Oberwürzbach
Germany	Praxis Dr. Herrmann	Schwabenheim
Germany	Praxis Dr. Dietlein	Stadtbergen
Germany	Praxis Dr. Sauter	Wangen
Germany	Schwerpunktpraxis Diabetologie	Zwenkau
Greece	General Hospital of Athens Evangelismos	Athens
Greece	General University Hospital "Attikon"	Haidari, Athens
Greece	Univ. Gen. Hosp. of Ioannina	Ioannina
Greece	General Hospital "Amalia Fleming"	Melissia, Athens
Greece	General Hospital of Nikaia	Nikaia
Greece	General Hopsital of Thessaloniki "Ippokrateio"	Thessaloniki
Greece	Kliniki Thermi	Thessaloniki
Greece	University General Hospital of Thessaloniki AHEPA	Thessaloniki
Hong Kong	Alice Ho Miu Ling Nethersole Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hungary	Imre Magyar Hospital, Ajka	Ajka
Hungary	Lausmed Kft. Outpatient Unit of Internal Medicine	Baja
Hungary	Karolyi Sandor Hospital, Budapest	Budapest
Hungary	Bekes County Pandy Kalman Hospital	Gyula
Hungary	Erzsebet Hospital, Hodmezövasarhely	Hódmezövásárhely
Hungary	Dr. Samuel Diosszilagyi Hospital and Outpatient Clinic, Mako	Mako
Hungary	TaNa Med Kft.	Mosonmagyarovar
Hungary	Grof Esterhazy Hospital and Outpatient Clinic	Papa
Hungary	Tolna County Balassa Janos Hospital	Szekszard
India	Shree Krishna Hospital and Heart Care Centre, Ahmedabad	Ahmedabad
India	CIIGMA Institute of Medical Sciences Pvt Ltd	Aurangabad
India	Bangalore Diabetes Centre (BDC)- Medisys Clinical Research	Bangalore
India	Diabetes care and research centre	Bangalore
India	Manipal Hospital	Bangalore
India	MS Ramaiah Memorial Hospital,	Bangalore, Karnataka
India	Belgaum Diabetes Centre, Belgaum	Belgaum
India	Apollo Hospitals	Chennai
India	Dr. Mohans Diabetes Speciality Centre	Chennai
India	M V Hospital For Diabetes and Diabetes Research Centre	Chennai
India	Swamy Diabetes Centre	Chennai
India	Kovai Diabetes Speciality Centre & Hospital	Coimbatore
India	TOTALL Diabetes Hormone Institute	Indore
India	Diabetes Thyroid and Endocrine Centre	Jaipur
India	Diamed Clinical Research Services Pvt. Ltd.	Jaipur
India	Grant Medical Foundation, Ruby Hall Clinic	Maharashtra
India	Global Hospital- Superspeciality & Transplant Centre	Mumbai
India	RHIDEM	Mumbai
India	K.G.N. Diabetes and Endocrine Centre	Mumbai, Maharastra
India	Sunil's Diabetes care and Research Centre	Nagpur
India	Deshmukh Clinic	Pune
India	Jahingir Clinical Development Centre	Pune
India	Diabetes Care Center	Thiruvananthapuram
India	Yalamanchi Hospitals & Research Centres Pvt Ltd.	Vijayawada
Ireland	The Red House Family Practice	Co. Cork
Ireland	Connolly Hospital Blanchardstown	Dublin
Ireland	The Palms GP Surgery	Gorey
Ireland	Fethard-on-Sea Medical Practice	Wexford
Israel	Barzilai Medical Center	Ashkelon
Israel	Rambam Medical Center	Haifa
Israel	Edith Wolfson Medical Center, Diabetic Unit, Holon	Holon
Israel	Hadassah Medical Center, Ein-Karem	Jerusalem
Israel	Western Galilee Hospital	Nahariya
Israel	The Chaim Sheba Medical Center Tel Hashomer	Tel Hashomer
Israel	Sourasky Medical Center	Tel-Aviv
Italy	Ospedale "SS. Trinità"	Cagliari
Italy	Policlinico Universitario Mater Domini, Universita di Catanzaro	Catanzaro
Italy	Policlinico San Martino	Genova
Italy	Ospedale di Guastalla	Guastalla (RE)
Italy	A.O.U.Policlinico G.Martino	Messina
Italy	Fondazione Centro San Raffaele del Monte Tabor	Milano
Italy	Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza	Roma
Italy	Ospedale S. Pertini	Roma
Italy	IRCCS Gruppo Multimedica	Sesto San Giovanni (MI)
Japan	Daishinkai Medical Corporation Ookuma Hospital	Aichi, Nagoya
Japan	Chibanishi General Hospital	Chiba, Matsudo
Japan	New Tokyo Heart Clinic	Chiba, Matsudo
Japan	Kashinoki I.M. Clinic, Fukushima, I.M.	Fukushima, Date
Japan	Japan Community Health care Organization Nihonmatsu Hospital	Fukushima, Nihonmatsu
Japan	Iwase General Hospital	Fukushima, Sukagawa
Japan	Iryohojinshadan Sasaki Clinic	Hyogo, Amagasaki
Japan	Takasagoseibu Hospital	Hyogo, Takasago
Japan	Kanagawa Cardiovascular and Respiratory Center	Kanagawa, Yokohama
Japan	Jinnouchi Clinic Diabetes Care Center	Kumamoto, Kumamoto
Japan	Kumamoto Rosai Hospital	Kumamoto, Yatsushiro
Japan	Koga General Hospital	Miyazaki, Miyazaki
Japan	Saitama Medical Cooperative Association Hanyu General Hospital	Saitama, Hanyu
Japan	Nihon University Itabashi Hospital	Tokyo, Itabashi-ku
Korea, Republic of	Korea University Ansan Hospital	Ansan
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Dongguk University Ilsan Hospital	Goyang
Korea, Republic of	Inje University Ilsan Paik Hospital	Goyang
Korea, Republic of	National Health Insurance Service Ilsan Hospital	Goyang
Korea, Republic of	Chonbuk National University Hospital	Jeonju
Korea, Republic of	Pusan National Univ. Hosp	Pusan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Kangdong Sacred Heart Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon
Korea, Republic of	Wonju Severance Christian Hosp	Wonju
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan
Malaysia	Monash University	Johor Bahru, Johor
Malaysia	Hospital University Sains Malaysia	Kota Bharu
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Tengku Ampuan Afzan	Kuantan
Malaysia	Hospital Melaka	Melaka
Malaysia	Penang Medical College	Penang
Malaysia	Hospital Taiping	Taiping
Mexico	Hospital General de Acapulco	Acapulco
Mexico	Centro de Investigacion Cardiometabolica de Aguascalientes	Aguascalientes
Mexico	Instituto Nacional de Cardiologia Ignacio Chavez	Distrito Federal
Mexico	Unidad de Investigacion Clinica Cardiometabolica de Occident	Guadalajara
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez	Monterrey
Netherlands	Huisartspraktijk Emmers	's-hertogenbosch
Netherlands	FlevoResearch	Almere
Netherlands	Academisch Medisch Centrum (AMC)	Amsterdam
Netherlands	Rode Kruis Ziekenhuis Beverwijk	Beverwijk
Netherlands	Andromed Breda	Breda
Netherlands	Noordwest Ziekenhuisgroep, location Den Helder	Den Helder
Netherlands	Andromed Eindhoven	Eindhoven
Netherlands	Andromed Noord	Groningen
Netherlands	Vasculair Onderzoek Centrum	Hoorn
Netherlands	Maastricht Universitair Medisch Centrum	Maastricht
Netherlands	Andromed Rotterdam	Rotterdam
Netherlands	Ikazia Ziekenhuis	Rotterdam
Netherlands	Rotterdam Research Institute	Rotterdam
Netherlands	Antonius Ziekenhuis	Sneek
Netherlands	Andromed Oost	Velp
Netherlands	Andromed Leiden-Zoetermeer	Zoetermeer
New Zealand	Christchurch Hospital	Christchurch
New Zealand	RMC Medical Research Ltd	Dunedin
New Zealand	P3 Research, Wellington	Newtown Wellington NZ
New Zealand	P3 Research, Promed House	Tauranga
Norway	Medi 3 AS	Ålesund
Norway	Bodø Legesenter AS, avd. for med. studier	Bodø
Norway	Medi 3 Innlandet AS, avd Elverum	Elverum
Norway	Vestre Viken HF, Bærum sykehus	Gjettum
Norway	M3 Helse AS	Hamar
Norway	Bylegene SA	Jessheim
Norway	Heiaklinikken	Lierskogen
Norway	Rådhuset Spesialistsenter	Oslo
Norway	Sandvika Spesialistsenter	Sandvika
Norway	Grålum Legesenter	Sarpsborg
Norway	Forusakutten - Kolibri Medical, Avd. Stavanger	Stavanger
Peru	Instituto Delgado de Investigacion Medica	Arequipa
Peru	Clinica San Pedro	Huacho
Peru	Centro de Investigaciones Médicas METABOLICARE SAC	Lima
Peru	Clinica Internacional	Lima
Peru	Clinica San Gabriel	Lima
Peru	Hospital Nacional Dos de Mayo	Lima
Peru	Centro De Especialidades Medicas Santa Maria S.A.C	Piura
Peru	Clinica San Judas Tadeo	San Miguel
Philippines	Center for Diabetes Care	Iloilo
Philippines	Mary Mediatrix Medical Center	Lipa City, Batangas
Philippines	Manila Doctors Hospital	Manila
Philippines	Philippine General Hospital	Manila
Philippines	University of Santo Tomas Hospital	Manila
Philippines	Asian Hospital & Medical Center	Muntinlupa
Philippines	Quirino Memorial Medical Center	Quezon City
Philippines	St. Luke's Medical Center	Quezon City
Philippines	Cardinal Santos Medical Center	San Juan
Philippines	Surigao Health Specialists	Surigao
Portugal	Hospital Fernando Fonseca, EPE	Amadora
Portugal	CHLO, EPE - Hospital de Santa Cruz	Carnaxide
Portugal	CHUC - Centro Hospitalar e Universitário de Coimbra, EPE	Coimbra
Portugal	Centro Hospitalar da Cova da Beira Hospital Pêro da Covilhã	Covilhã
Portugal	Hospital Distrital Figueira da Foz, EPE	Figueira da Foz
Portugal	Hospital da Luz	Lisboa
Portugal	Centro Hospitalar São João,EPE	Porto
Portugal	Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião	Santa Maria da Feira
Romania	SC Diabol SRL, Brasov	Brasov
Romania	Nicodiab SRL, Bucharest	Bucharest
Romania	SC Medical Centre "Sanatatea Ta" SRL, Bucharest	Bucharest
Romania	Consultmed SRL, Iasi	Iasi
Romania	Emergency County Clinical Hospital, Sibiu	Sibiu
Romania	Private Practice Dr. Remus Gagiu	Tirgoviste
Russian Federation	LLC Clinic of new technologies of medicine	Dzerzhinsky
Russian Federation	City Clinical Hospital No. 6 of MoH of Udmurt Republic	Izhevsk
Russian Federation	City Clinical Hospital No. 13, Moscow	Moscow
Russian Federation	City Clinical Hospital No. 4, Moscow	Moscow
Russian Federation	City Clinical Hospital No. 61, Moscow	Moscow
Russian Federation	State Institution "Central Clinical Hospital of RAS", Moscow	Moscow
Russian Federation	State Healthcare Institution, Regional hospital #2	Rostov-na-Donu
Russian Federation	Limited Liability Company "CENTER DIABET", Samara	Samara
Russian Federation	MMU City Outpatient Clinic no. 20, Saratov	Saratov
Serbia	Clinical Medical Center Zvezdara, Belgrade	Belgrade
Serbia	Clinical Centre Nis	Nis
Serbia	General Hospital Pancevo	Pancevo
Serbia	General Hospital Subotica, Internal Medicine	Subotica
Serbia	Clinical Hospital Center Zemun	Zemun
Slovakia	DIASTYLE s.r.o., Diabetology Outpatient Department	Banska Bystrica
Slovakia	ENDIAMED s.r.o., Dolny Kubin	Dolny Kubin
Slovakia	CELL B s.r.o.	Levice
Slovakia	DIA-KONTROL s.r.o.	Levice
Slovakia	Funkystuff s.r.o., Nove Zamky	Nove Zamky
Slovakia	Diabetologicka ambulancia MUDr. Lucia Gajdosikova s.r.o.	Povazska Bystrica
Slovakia	MEDIVASA s.r.o., Outpatient Clinic, Zilina	Zilina
South Africa	Dr. E. L. Janari	Cape Town
South Africa	Dr. P. Patel	Cape Town
South Africa	Dr. Vawda	Durban
South Africa	Parklands Medical Centre	Durban
South Africa	Dr. Jurgens	Krugersdorp
South Africa	Dr. D. R. Lakha, Johannesburg	Lenasia
South Africa	Dr. H. Makan	Lenasia
South Africa	Greenacres Hospital	Port Elizabeth
South Africa	Dr. M. Seeber	Pretoria
South Africa	Vergelegen Medi-Clinic	Somerset West
Spain	C.A.P. Sardenya	Barcelona
Spain	CAP Casanova	Barcelona
Spain	CAP Les Corts	Barcelona
Spain	CAP Burjassot 1	Burjassot
Spain	C.S. Natahoyo	Gijon
Spain	Hospital Universitari de Girona Doctor Josep Trueta	Girona
Spain	CAP Florida	L'Hospitalet de Llobregat
Spain	Hospital de Bellvitge	L'Hospitalet de Llobregat
Spain	CAP La Roca	La Roca Del Vallés (Barcelona)
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	C.S. Colloto	Oviedo
Spain	C.S. El Cristo	Oviedo
Spain	C.S. Vallobin-La Florida	Oviedo
Spain	ABS Pineda de Mar	Pineda de Mar
Spain	Hospital de l'Esperit Sant	Santa Coloma De Gramanet
Spain	CAP Tàrrega	Tàrrega
Spain	CS Ingeniero Joaquin Benlloch	Valencia
Spain	Hospital Clínico de Valencia	Valencia
Sweden	CTC Sahlgrenska Universitetssjukhuset	Göteborg
Sweden	Sjukhuset, Härnösand	Härnösand
Sweden	Avonova Hälsa AB	Järfälla
Sweden	Skånes universitetssjukhus, Malmö	Malmö
Sweden	Dalecarlia Clinical Research Center	Rättvik
Sweden	Södra Dalarnas vårdcentral, Hedemora	Rättvik
Sweden	Näsets Läkargrupp	Skanör
Sweden	Vårdcentralen Silentzvägen	Uddevalla
Sweden	S3 Clinical Research Centers	Vällingby
Switzerland	Allgemeine Medizin	Basel
Switzerland	FMH endocrinologia diabetologia	Bellinzona
Switzerland	Inselspital Bern	Bern
Switzerland	Dr. Pietro Gerber	Lugano
Taiwan	Chang-Hua Christian Hospital	Changhua
Taiwan	E-Da Hospital	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Far Eastern Memorial Hospital	New Taipei City
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung,
Taiwan	NCKUH	Tainan
Taiwan	Cardinal Tien Hospital	Taipei
Taiwan	Cheng Hsin General Hospital	Taipei
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Shih-Kong Wu Ho-Shu Memorial Hospital	Taipei
Taiwan	Taipe Veterans General Hospital	Taipei
Taiwan	Taipei Medical University-Shuang Ho Hospital	Taipei
Taiwan	Tri-Service General Hospital	Taipei
Tunisia	HOP Fattouma Bourguiba, Mint, Monastir	Monastir
Tunisia	HOP Hédi Chaker, Endo, Sfax	Sfax
Tunisia	HOP Farhat Hached, Mint, Sousse	Sousse
Tunisia	HOP Habib Thameur, Mint, Tunis	Tunis
Ukraine	Donetsk Regional Clinical Hosp, Therapy Department	Donetsk
Ukraine	Ivano-Frankivsk City Central Clinical Hospital	Ivano-Frankivsk
Ukraine	City Clinical Hospital No. 17, Kharkov	Kharkiv
Ukraine	City Clinical Hospital No. 27, Kharkiv	Kharkov
Ukraine	City Clinical Hospital No. 1, Kiev	Kiev
Ukraine	Clinic for Cardiology "Sertse i sudyny", Kiev	Kiev
Ukraine	Poliklinika #2, Kyiv	Kyiv
Ukraine	City Hospital No. 5, Lvov	Lvov
Ukraine	Odeska zaliznichna likarnya, Odessa	Odesa
Ukraine	Vinnitsia Regional Endocrinology Dispensary	Vinnitsa
United Kingdom	Crouch Oak Family Practice	Addlestone
United Kingdom	Ash Vale Health Centre, Aldershot	Ash Vale, Aldershot
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Hathaway Medical Centre	Chippenham
United Kingdom	University Hospital of North Durham	Durham
United Kingdom	St Mary's Surgery	Ely
United Kingdom	Gloucestershire Royal Hospital	Gloucester
United Kingdom	James Paget University Hospital	Great Yarmouth
United Kingdom	Morriston Hospital	Swansea
United Kingdom	Royal Cornwall Hospital	Truro
United States	Community Health Care of Manchester	Akron	Ohio
United States	Albany Medical Center / Albany Medical College	Albany	New York
United States	Hartwell Research Group, LLC	Anderson	South Carolina
United States	KRK Medical Research	Arlington	Texas
United States	OnSite Clinical Solutions, LLC	Asheville	North Carolina
United States	Atco Medical Associates, PC	Atco	New Jersey
United States	North Alabama Research Center, LLC	Athens	Alabama
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	PMI Health Research Group	Atlanta	Georgia
United States	Austin Center for Clinical Research	Austin	Texas
United States	Community Medical Associates, LLC	Austintown	Ohio
United States	American Health Network	Avon	Indiana
United States	Office of Dr. Stephen R. Smith, MD	Baltimore	Maryland
United States	Acadia Clinical Research, LLC	Bangor	Maine
United States	Desert Oasis Healthcare	Bermuda Dunes	California
United States	The Center for Clinical Trials, Inc.	Biloxi	Mississippi
United States	Alabama Internal Medicine, PC	Birmingham	Alabama
United States	Cahaba Research, Inc.	Birmingham	Alabama
United States	East Coast Medical Associates	Boca Raton	Florida
United States	Suburban Clinical Research	Bolingbrook	Illinois
United States	PMG Research of Bristol	Bristol	Tennessee
United States	Investigators Research Group, LLC	Brownsburg	Indiana
United States	Burke Internal Medicine and Research	Burke	Virginia
United States	Kernodle Clinic West	Burlington	North Carolina
United States	Harrison Community Research Center	Cadiz	Ohio
United States	ClinSite, LLC	Canton	Michigan
United States	Medical Frontiers, LLC	Carlisle	Ohio
United States	Punzi Medical Center	Carrollton	Texas
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Gaffney Health Services	Charlotte	North Carolina
United States	Internal Medicine Research	Charlotte	North Carolina
United States	University Diabetes and Endocrine Consultants	Chattanooga	Tennessee
United States	Apex Medical Research	Chicago	Illinois
United States	Cedar-Crosse Research Center	Chicago	Illinois
United States	John H. Stroger Jr. Hospital of Cook Country	Chicago	Illinois
United States	Summit Medical Group	Clifton	New Jersey
United States	Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC	Colorado Springs	Colorado
United States	Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC	Colorado Springs	Colorado
United States	New England Center for Clinical Research, Inc	Cranston	Rhode Island
United States	Baylor Endocrine Center	Dallas	Texas
United States	Dallas Diabetes and Endocrine Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Todd Kazdan, DO Family Practice	Davie	Florida
United States	Century Clinical Research, Inc	Daytona Beach	Florida
United States	Doral Research Center	Doral	Florida
United States	Albert F. Johary MD, PC	Dunwoody	Georgia
United States	Durham Internal Medicine Associates	Durham	North Carolina
United States	Riverside Clinical Research	Edgewater	Florida
United States	Central Jersey Medical Research	Elizabeth	New Jersey
United States	USMA Clinical Research	Elizabeth	New Jersey
United States	Sentara Family Medicine	Elizabeth City	North Carolina
United States	Ettrick Health Center	Ettrick	Virginia
United States	Oregon Medical Group	Eugene	Oregon
United States	Pharmakon Inc	Evergreen Park	Illinois
United States	Larry D Stonesifer, MD Inc., PS	Federal Way	Washington
United States	Apex Medical Research, AMR Inc	Flint	Michigan
United States	MCM Clinical Research, LLC	Florence	Kentucky
United States	Alan Graff, MD, PA	Fort Lauderdale	Florida
United States	M & O Clinical Research, LLC	Fort Lauderdale	Florida
United States	Edinger Medical Group and Research Center	Fountain Valley	California
United States	American Health Network of Indiana, LLC	Franklin	Indiana
United States	Clinical Trials of St. Jude Heritage Med. Group	Fullerton	California
United States	Genoa Medical Center	Genoa	Ohio
United States	Paris View Family Practice	Greenville	South Carolina
United States	Mountain View Clinical Research	Greer	South Carolina
United States	Harleysville Medical Associates	Harleysville	Pennsylvania
United States	Hayden Lake Family Physicians	Hayden Lake	Idaho
United States	Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC	Henderson	Nevada
United States	Eastern Research	Hialeah	Florida
United States	Research in Miami Inc	Hialeah	Florida
United States	Clinical Trial Network	Houston	Texas
United States	Endocrine and Psychiastry Center	Houston	Texas
United States	Jacon Medical Research Associates, LLC	Houston	Texas
United States	JVC Family Medicine	Houston	Texas
United States	Pioneer Research Solutions, Inc.	Houston	Texas
United States	American Health Network, LLC	Indianapolis	Indiana
United States	Mapleton Medical Center	Indianapolis	Indiana
United States	Care Partners Clinical Research LLC	Jacksonville	Florida
United States	East Coast Institute for Research, LLC	Jacksonville	Florida
United States	Jacksonville Impotence Treatment Center	Jacksonville	Florida
United States	Northeast Arkansas Baptist Clinic	Jonesboro	Arkansas
United States	Westside Family Medical Center, PC	Kalamazoo	Michigan
United States	Detweiler Family Medicine & Associates, PC	Lansdale	Pennsylvania
United States	Clinical Research of South Nevada	Las Vegas	Nevada
United States	Palm Medical Research Center	Las Vegas	Nevada
United States	Precision Clinical Research, LLC	Lauderdale Lakes	Florida
United States	Kentucky Diabetes Endocrinology Center	Lexington	Kentucky
United States	Aureus Research, Inc	Little Rock	Arkansas
United States	Medical Investigations, Inc	Little Rock	Arkansas
United States	Tri City Medical Centers, PC	Livonia	Michigan
United States	Long Beach Center for Clinical Research	Long Beach	California
United States	Office of Dr. Richard S. Cherlin	Los Gatos	California
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Office of Dr. Craig S. Thompson, MD, LLC	Marion	Ohio
United States	RAS Health Limited	Marion	Ohio
United States	Advanced Medical Research, LLC	Maumee	Ohio
United States	University of Tennessee	Memphis	Tennessee
United States	Boise Kidney and Hypertension Institute	Meridian	Idaho
United States	Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC	Mesa	Arizona
United States	Clinical Research Advantage, Inc./Rita B. Chuang, MD, LLC	Mesa	Arizona
United States	Crescent City Clinical Research	Metairie	Louisiana
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	APF Research, LLC	Miami	Florida
United States	AppleMed Research Group, LLC	Miami	Florida
United States	Kendall South Medical Center, Inc	Miami	Florida
United States	South Miami Clinical Research	Miami	Florida
United States	Swiss Medical Research	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Veritas Research Corporation	Miami	Florida
United States	Well Pharma Medical Research	Miami	Florida
United States	Midland Clinical Research Center	Midland	Texas
United States	PHS Clinical Trials	Midvale	Utah
United States	Park Nicollet Institute	Minneapolis	Minnesota
United States	McKinley Research, LLC	Mishawaka	Indiana
United States	Diagnostic and Medical Clinic	Mobile	Alabama
United States	Internal Medicine Center, LLC	Mobile	Alabama
United States	Extended Arm Physicians, Inc.	Montgomery	Alabama
United States	American Health Network of Indiana, LLC	Muncie	Indiana
United States	Hill Country Medical Associates	New Braunfels	Texas
United States	Advanced Research Institute, Inc	New Port Richey	Florida
United States	Suncoast Clinical Research, Inc.	New Port Richey	Florida
United States	Tristan Medical Enterprises, PC dba Regeneris	North Attleboro	Massachusetts
United States	Providence Clinical Research	North Hollywood	California
United States	Naidu Clinic	Odessa	Texas
United States	Infinity Research Group, LLC	Oklahoma City	Oklahoma
United States	Quality Clinical Research	Omaha	Nebraska
United States	Sunshine Research Center	Opa-locka	Florida
United States	South Carolina Nephrology and Hypertension Center, Inc	Orangeburg	South Carolina
United States	Diabetes and Endocrine Center of Orlando	Orlando	Florida
United States	Four Rivers Clinical Research, Inc	Paducah	Kentucky
United States	Suncoast Clinical Research	Palm Harbor	Florida
United States	Misal Khan, MD FRCS, ED, PA	Panama City	Florida
United States	The Methodist Hospital d/b/a HMRI CCAT at Pearland	Pearland	Texas
United States	Advanced Clinical Research	Pell City	Alaska
United States	Iconic Clinical Trials	Pembroke Pines	Florida
United States	Gulf Region Clinical Research Institute	Pensacola	Florida
United States	Temple University School of Medicine	Philadelphia	Pennsylvania
United States	Village Health Partners	Plano	Texas
United States	Chaparral Medical Group, Inc	Pomona	California
United States	St. John's Center for Clinical Research	Ponte Vedra Beach	Florida
United States	PMG Research of Raleigh, LLC	Raleigh	North Carolina
United States	ARI Clinical Trials, Inc	Redondo Beach	California
United States	Clinical Research Partners, LLC	Richmond	Virginia
United States	Richmond Family Practice	Richmond	Virginia
United States	Endocrine and Metabolic Consultants	Rockville	Maryland
United States	KMED Research	Saint Clair Shores	Michigan
United States	Mercy Health Research	Saint Louis	Missouri
United States	Highland Clinical Research	Salt Lake City	Utah
United States	Sun Research Institute	San Antonio	Texas
United States	San Diego Sports Medicine and Family Health Center	San Diego	California
United States	West Coast Research, LLC	San Ramon	California
United States	Northeast Clinical Research of San Antonio, LLC	Schertz	Texas
United States	Carolina Research Center, Inc	Shelby	North Carolina
United States	Endocrine Associates of Long Island, PC	Smithtown	New York
United States	Georgia Clinical Research, LLC	Snellville	Georgia
United States	Premier Clinical Research	Spokane	Washington
United States	Piedmont Healthcare	Statesville	North Carolina
United States	Tri-County Research, Inc	Sterling Heights	Michigan
United States	Kenneth Otah and Associates	Sugar Land	Texas
United States	Carolina Diabetes & Kidney Center	Sumter	South Carolina
United States	University of California Los Angeles	Sylmar	California
United States	Metabolic Institute of America	Tarzana	California
United States	Medical Research Associates	Traverse City	Michigan
United States	Oakland Medical Research Center	Troy	Michigan
United States	Genova Clinical Research	Tucson	Arizona
United States	Quality of Life Medical & Research Center	Tucson	Arizona
United States	Trinity Clinical Research, LLC	Tullahoma	Tennessee
United States	Castlerock Clinical Research Consultants, LLC	Tulsa	Oklahoma
United States	Office of Dr. Terence T. Hart MD	Tuscumbia	Alabama
United States	Matrix Research Institute	Tustin	California
United States	Orange County Research Center	Tustin	California
United States	Warminster Medical Associates, PC	Warminster	Pennsylvania
United States	Metabolic Research Institute	West Palm Beach	Florida
United States	Southgate Medical Group/ Southgate Medical Park	West Seneca	New York
United States	Westlake Medical Research	Westlake Village	California
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina
United States	Pharmacotherapy Research Associates, Inc	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Czechia,  Finland,  France,  Georgia,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Norway,  Peru,  Philippines,  Portugal,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Tunisia,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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