VERIFY:A Study to Compare Combination Regimen With Vildagliptin & Metformin Versus Metformin in Treatment-naïve Patients With Type 2 Diabetes Mellitus

NCT ID: NCT01528254

Last Updated: 2020-09-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

2004 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-03-30

Study Completion Date

2019-04-04

Brief Summary

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The purpose of this study was to determine whether the initiation of a vildagliptin plus metformin combination regimen would result in more durable glycemic control than metformin monotherapy in treatment-naïve patients with type-2 diabetes mellitus (T2DM).

Detailed Description

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This was a multi-center, double-blind, placebo-controlled, 2-arm, parallel group study with a run-in period and up to 5 years treatment period. Following a screening visit (Visit 1) and a screening period of up to 2 weeks, treatment-naïve patients, meeting all eligibility criteria entered the run-in period at Visit 2.

* Run-in period: At Visit 2, in all eligible patients, metformin treatment was initiated and/or up-titrated. At the end of the 3-week run-in period, patients who were able to tolerate a total dose of at least 1000 mg and up to 2000 mg daily proceeded to randomization and started in Period 1.
* Period 1 (vildagliptin/metformin combination versus metformin): At Visit 3, patients were randomized 1:1 to one of the following study regimens:

* Metformin up to 1000 mg bid plus vildagliptin 50mg bid or
* Metformin up to 1000 mg bid plus matching placebo bid

The duration of Period 1 could differ between patients depending on the time when the second of two HbA1c measurements taken at two consecutive visits after randomisation confirmed HbA1c ≥ 7.0%.

• Period 2 (vildagliptin/metformin combination versus vildagliptin add-on to metformin): In the case of two consecutive HbA1c measurements ≥7.0% from two consecutive study visits during Period 1, patients who were randomised to the placebo arm in Period 1 received vildagliptin 50 mg bid. Patients who were randomised to the active vildagliptin 50 mg bid arm in Period 1 continued to receive vildagliptin 50 mg bid. All patients continued to take their metformin dose unchanged. Period 2 remained masked to the patient and both patients and investigators remained masked to the treatment allocation in Period 1.

If, during Period 2, therapy intensification was required in accordance with the local guidelines, the patient entered Period 3. The duration of Period 2 could differ between patients. End of Period 2 was considered when insulin treatment was initiated, or alternatively when the patient was discontinued because insulin treatment was not initiated in Period 3.

• Period 3 (insulin initiation): In Period 3, patients were to be initiated on open-label insulin. The study drug regimen continued unchanged and remained masked to the patient in Period 3 and both patients and investigators remained masked to the treatment allocation in Period 1.

Conditions

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Type 2 Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Vilda 50mg bid + metformin

Metformin + vildagliptin

Group Type ACTIVE_COMPARATOR

vildagliptin

Intervention Type DRUG

One tablet (50 mg oral) of vildagliptin in the morning and one tablet in the evening with or without food.

Metformin

Intervention Type DRUG

Twice daily (bid) regimen during or after meals at the same time as vildagliptin.

Placebo + metformin

Metformin + Placebo of vildagliptin

Group Type EXPERIMENTAL

Placebo of vildagliptin

Intervention Type DRUG

Metformin

Intervention Type DRUG

Twice daily (bid) regimen during or after meals at the same time as vildagliptin.

Interventions

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Placebo of vildagliptin

Intervention Type DRUG

vildagliptin

One tablet (50 mg oral) of vildagliptin in the morning and one tablet in the evening with or without food.

Intervention Type DRUG

Metformin

Twice daily (bid) regimen during or after meals at the same time as vildagliptin.

Intervention Type DRUG

Other Intervention Names

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Placebo LAF237

Eligibility Criteria

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Inclusion Criteria

* Type 2 Diabetes Mellitus (T2DM) diagnosed ≤ 24 months ago
* glycosylated hemoglobin (HbA1c) ≥6.5% and ≤7.5% at Visit 1
* Treatment-naïve.
* Body mass index (BMI) ≥22 and ≤40 kg/m2 at Visit 1

Exclusion Criteria

* Pregnant or nursing (lactating) women
* Fasting plasma glucose (FPG) ≥ 270 mg/dL (≥ 15.0 mmol/L)
* Previous or current participation in any vildagliptin clinical study.
* History of hypersensitivity to dipeptidyl peptidase-4 (DPP-4) inhibitors.
* Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study.
* Donation of blood or significant blood loss equaling to at least one unit of blood within the past 2 weeks of start of study or a blood transfusion within the past 12 weeks or planned regular transfusions during the study period.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

CABA, Buenos Aires, Argentina

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CABA, Buenos Aires, Argentina

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San Isidro, Buenos Aires, Argentina

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CABA, Buenos Aires F.D., Argentina

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Buenos Aires, , Argentina

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Corrientes, , Argentina

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Córdoba, , Argentina

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Brookvale, New South Wales, Australia

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Woy Woy, New South Wales, Australia

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Morayfield, Queensland, Australia

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Vienna, , Austria

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Fortaleza, Ceará, Brazil

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Fortaleza, Ceará, Brazil

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Brasília, Federal District, Brazil

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Goiânia, Goiás, Brazil

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Curitiba, Paraná, Brazil

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Belém, Pará, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Mogi das Cruzes, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Smolyan, Bulgaria, Bulgaria

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Gabrovo, , Bulgaria

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Kazanlak, , Bulgaria

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Plovdiv, , Bulgaria

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Razgrad, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Bogota, Cundinamarca, Colombia

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Cartagena, Departamento de Bolívar, Colombia

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Baranquilla, , Colombia

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Bogotá, , Colombia

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Písek, Czech Republic, Czechia

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Prague, Czech Republic, Czechia

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Brandýs nad Labem, , Czechia

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Prague, , Czechia

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Santo Domingo, Republica Dominicana, Dominican Republic

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Santo Domingo, , Dominican Republic

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Saku, , Estonia

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Tallinn, , Estonia

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Tallinn, , Estonia

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Tallinn, , Estonia

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Tallinn, , Estonia

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Lahti, Suomi, Finland

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Kerava, , Finland

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Kouvola, , Finland

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Tampere, , Finland

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Hainstadt, Hainburg, Germany

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Aschaffenburg, , Germany

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Cologne, , Germany

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Ludwigshafen, , Germany

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Neuwied, , Germany

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Saint Ingbert - Oberwuerzbach, , Germany

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Wangen, , Germany

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Clinica, Departamento de Guatemala, Guatemala

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Csongrád, , Hungary

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Eger, , Hungary

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Kalocsa, , Hungary

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Szeged, , Hungary

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Bangalore, Karnataka, India

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New Delhi, National Capital Territory of Delhi, India

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Chennai, Tamil Nadu, India

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Chandigarh, , India

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Haifa, Israel, Israel

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Jerusalem, , Israel

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Kfar Saba, , Israel

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Rehovot, , Israel

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Sefad, , Israel

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Tel Aviv, , Israel

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Tel Giborim, Holon, , Israel

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Montichiari, BS, Italy

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Campobasso, CB, Italy

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Arenzano, GE, Italy

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Milan, MI, Italy

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Milan, MI, Italy

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Casorate Primo, PV, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Jelgava, LV, Latvia

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Liepāja, LV, Latvia

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Talsi, LV, Latvia

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Kaunas, LTU, Lithuania

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Vilnius, LT, Lithuania

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Kaunas, , Lithuania

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Kota Bharu, Kelantan, Malaysia

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Kuala Lumpur, , Malaysia

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Kuala Lumpur, , Malaysia

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Mexico City, Mexico City, Mexico

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Mexico City, Mexico City, Mexico

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Mexico City, Mexico City, Mexico

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Cuautla, Morelos, Mexico

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Cuernavaca, Morelos, Mexico

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Aguascalientes, , Mexico

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Distrito Federal, , Mexico

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Durango, , Mexico

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Querétaro, , Mexico

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Enebakk, , Norway

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Fetsund, , Norway

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Hønefoss, , Norway

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Oslo, , Norway

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Spikkestad, , Norway

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Panama City, , Panama

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Panama City, , Panama

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Trujillo, La Libertad, Peru

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Chorrillos, Lima region, Peru

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Lima Cercado, Lima region, Peru

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Magdalena, Lima region, Peru

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San Isidro, Lima region, Peru

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San Martín de Porres, Lima region, Peru

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Arequipa, , Peru

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Marikina City, National Capital Region, Philippines

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Quezon City, National Capital Region, Philippines

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Pasay, Philippines, Philippines

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Marikina City, , Philippines

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Pasig, , Philippines

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San Juan City, , Philippines

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Poznan, , Poland

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Poznan, , Poland

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Poznan, , Poland

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Wroclaw, , Poland

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Zabrze, , Poland

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Oradea, Bihor County, Romania

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Oradea, Jud. Bihor, Romania

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Ploieşti, Jud. Prahova, Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Bucharest, , Romania

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Timișoara, , Romania

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Moscow, , Russia

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N.Novgorod, , Russia

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Penza, , Russia

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Petrozavodsk, , Russia

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Ryazan, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saratov, , Russia

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Smolensk, , Russia

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Bratislava, Slovak Republic, Slovakia

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Košice, Slovak Republic, Slovakia

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Lučenec, Slovak Republic, Slovakia

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Námestovo, Slovak Republic, Slovakia

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Rožňava, Slovak Republic, Slovakia

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Šaľa, Slovak Republic, Slovakia

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Trebišov, Slovak Republic, Slovakia

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Žilina, Slovak Republic, Slovakia

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Banská Bystrica, , Slovakia

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Košice, , Slovakia

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Košice, , Slovakia

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Levice, , Slovakia

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Nové Zámky, , Slovakia

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Prešov, , Slovakia

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Sabinov, , Slovakia

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Sereď, , Slovakia

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Štúrovo, , Slovakia

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Žilina, , Slovakia

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Alberton, , South Africa

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Cape Town, , South Africa

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Durban, , South Africa

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Durban, , South Africa

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Gauteng, , South Africa

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Johannesburg, , South Africa

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Johannesburg, , South Africa

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Pretoria, , South Africa

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Pretoria, , South Africa

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Incheon, Gyeonggi-do, South Korea

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Suwon, Gyeonggi-do, South Korea

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Uijeongbu-si, Gyeonggi-do, South Korea

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Seoul, Korea, South Korea

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Seoul, Seocho Gu, South Korea

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Daejeon, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Sant Adria Del Besos, Barcelona, Spain

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Santa Coloma de Gramanet, Barcelona, Spain

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Barcelona, Catalonia, Spain

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Barcelona, , Spain

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taoyuan District, , Taiwan

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Xindian District, , Taiwan

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Diskapi / Ankara, Turkey, Turkey (Türkiye)

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Adana, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Denizli, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kahramanmaraş, , Turkey (Türkiye)

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Countries

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Argentina Australia Austria Brazil Bulgaria Colombia Czechia Dominican Republic Estonia Finland Germany Guatemala Hong Kong Hungary India Israel Italy Latvia Lithuania Malaysia Mexico Norway Panama Peru Philippines Poland Romania Russia Slovakia South Africa South Korea Spain Taiwan Turkey (Türkiye)

References

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Tsotra F, Kappel M, Peristeris P, Bader G, Levi E, Lister N, Malhotra A, Ostwald DA. The societal impact of early intensified treatment in patients with type 2 diabetes mellitus. J Comp Eff Res. 2022 Nov;11(16):1185-1199. doi: 10.2217/cer-2022-0110. Epub 2022 Sep 28.

Reference Type DERIVED
PMID: 36170017 (View on PubMed)

Vencio S, Manosalva JP, Mathieu C, Proot P, Lozno HY, Paldanius PM. Exploring early combination strategy in Latin American patients with newly diagnosed type 2 diabetes: a sub-analysis of the VERIFY study. Diabetol Metab Syndr. 2021 Jun 15;13(1):68. doi: 10.1186/s13098-021-00686-9.

Reference Type DERIVED
PMID: 34130731 (View on PubMed)

Matthews D, Del Prato S, Mohan V, Mathieu C, Vencio S, Chan JCN, Stumvoll M, Paldanius PM. Insights from VERIFY: Early Combination Therapy Provides Better Glycaemic Durability Than a Stepwise Approach in Newly Diagnosed Type 2 Diabetes. Diabetes Ther. 2020 Nov;11(11):2465-2476. doi: 10.1007/s13300-020-00926-7. Epub 2020 Sep 25.

Reference Type DERIVED
PMID: 32975711 (View on PubMed)

Matthews DR, Paldanius PM, Proot P, Chiang Y, Stumvoll M, Del Prato S; VERIFY study group. Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year, multicentre, randomised, double-blind trial. Lancet. 2019 Oct 26;394(10208):1519-1529. doi: 10.1016/S0140-6736(19)32131-2. Epub 2019 Sep 18.

Reference Type DERIVED
PMID: 31542292 (View on PubMed)

Matthews DR, Paldanius PM, Proot P, Foley JE, Stumvoll M, Del Prato S. Baseline characteristics in the VERIFY study: a randomized trial assessing the durability of glycaemic control with early vildagliptin-metformin combination in newly diagnosed Type 2 diabetes. Diabet Med. 2019 Apr;36(4):505-513. doi: 10.1111/dme.13886. Epub 2019 Feb 12.

Reference Type DERIVED
PMID: 30576013 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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2011-003712-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLAF237A23156

Identifier Type: -

Identifier Source: org_study_id

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