NCT00790205

Brief Summary

This is a clinical trial designed to assess the cardiovascular outcome of long-term treatment with sitagliptin used as part of usual care compared to usual care without sitagliptin in participants with type 2 diabetes mellitus (T2DM) having a history of cardiovascular (CV) disease and a hemoglobin A1c (HbA1c) of 6.5% to 8.0%. Primary hypothesis A is that sitagliptin, when used as part of usual care, is non-inferior to usual care without sitagliptin with regard to the risk of developing a confirmed event in the primary CV composite endpoint of Major Adverse Cardiovascular Event (MACE) plus. If hypothesis A is satisfied: hypothesis B is that sitagliptin, when used as part of usual care, is superior to usual care without sitagliptin with regard to the risk of developing a confirmed event in the primary CV composite endpoint.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14,671

participants targeted

Target at P75+ for phase_3 type-2-diabetes-mellitus

Timeline
Completed

Started Dec 2008

Longer than P75 for phase_3 type-2-diabetes-mellitus

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 11, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 13, 2008

Completed
27 days until next milestone

Study Start

First participant enrolled

December 10, 2008

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 30, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 30, 2015

Completed
1 year until next milestone

Results Posted

Study results publicly available

April 15, 2016

Completed
Last Updated

November 23, 2021

Status Verified

October 1, 2021

Enrollment Period

6.3 years

First QC Date

November 11, 2008

Results QC Date

March 15, 2016

Last Update Submit

October 27, 2021

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (2)

  • Percentage of Participants With First Confirmed Cardiovascular (CV) Event of Major Adverse Cardiovascular Event (MACE) Plus (Per Protocol Population)

    Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

    Up to 5 years

  • Percentage of Participants With First Confirmed CV Event of Major Adverse Cardiovascular Event (MACE) Plus (Intent to Treat Population)

    Primary composite CV endpoint of MACE plus which includes CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization.

    Up to 5 years

Secondary Outcomes (16)

  • Percentage of Participants With First Confirmed CV Event of MACE (Per Protocol Population)

    Up to 5 years

  • Percentage of Participants With First Confirmed CV Event of MACE (Intent to Treat Population)

    Up to 5 years

  • Percent Incidence of All-cause Mortality (Per Protocol Population)

    Up to 5 years

  • Percent Incidence of All-cause Mortality (Intent to Treat Population)

    Up to 5 years

  • Percent Incidence of Congestive Heart Failure (CHF) Requiring Hospitalization (Per Protocol Population)

    Up to 5 years

  • +11 more secondary outcomes

Study Arms (2)

Sitagliptin

EXPERIMENTAL

Sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years.

Drug: Sitagliptin

Placebo

PLACEBO COMPARATOR

Placebo to sitagliptin tablet taken orally once daily in the morning for up to approximately 5 years.

Drug: Placebo

Interventions

SitagliptinDRUG

Sitagliptin, one 50 mg or one 100 mg tablet (dose dependant on renal function) orally, once daily.

Also known as: MK-0431, Januvia®
Sitagliptin
PlaceboDRUG

Placebo tablet matching the 50 mg or 100 mg sitagliptin tablet, orally, once daily.

Placebo

Eligibility Criteria

Age50 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Has T2DM
  • Has HbA1c between 6.5% (48 mmol/mol) and 8.0% (64 mmol/mol) on stable dose(s) of antihyperglycemic agent(s), including insulin
  • Has pre-existing cardiovascular disease

You may not qualify if:

  • Has a history of type 1 diabetes mellitus or ketoacidosis.
  • Is not able to take sitagliptin

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (19)

  • Green JB, Bethel MA, Paul SK, Ring A, Kaufman KD, Shapiro DR, Califf RM, Holman RR. Rationale, design, and organization of a randomized, controlled Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in patients with type 2 diabetes and established cardiovascular disease. Am Heart J. 2013 Dec;166(6):983-989.e7. doi: 10.1016/j.ahj.2013.09.003. Epub 2013 Oct 23.

    PMID: 24268212RESULT

  • Bethel MA, Green JB, Milton J, Tajar A, Engel SS, Califf RM, Holman RR; TECOS Executive Committee. Regional, age and sex differences in baseline characteristics of patients enrolled in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Diabetes Obes Metab. 2015 Apr;17(4):395-402. doi: 10.1111/dom.12441. Epub 2015 Feb 13.

    PMID: 25600421RESULT

  • Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, Josse R, Kaufman KD, Koglin J, Korn S, Lachin JM, McGuire DK, Pencina MJ, Standl E, Stein PP, Suryawanshi S, Van de Werf F, Peterson ED, Holman RR; TECOS Study Group. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2015 Jul 16;373(3):232-42. doi: 10.1056/NEJMoa1501352. Epub 2015 Jun 8.

    PMID: 26052984RESULT

  • Gao N, Dakin HA, Holman RR, Lim LL, Leal J, Clarke P. Estimating Risk Factor Time Paths Among People with Type 2 Diabetes and QALY Gains from Risk Factor Management. Pharmacoeconomics. 2024 Sep;42(9):1017-1028. doi: 10.1007/s40273-024-01398-4. Epub 2024 Jun 26.

    PMID: 38922488DERIVED

  • Bethel MA, Sourij H, Stevens SR, Hannan K, Lokhnygina Y, Adler AI, Peterson ED, Holman RR, Lopes RD. Time-dependent event accumulation in a cardiovascular outcome trial of patients with type 2 diabetes and established atherosclerotic cardiovascular disease. Cardiovasc Diabetol. 2023 Mar 28;22(1):72. doi: 10.1186/s12933-023-01802-x.

    PMID: 36978066DERIVED

  • Sharma A, Zheng Y, Ezekowitz JA, Westerhout CM, Udell JA, Goodman SG, Armstrong PW, Buse JB, Green JB, Josse RG, Kaufman KD, McGuire DK, Ambrosio G, Chuang LM, Lopes RD, Peterson ED, Holman RR. Cluster Analysis of Cardiovascular Phenotypes in Patients With Type 2 Diabetes and Established Atherosclerotic Cardiovascular Disease: A Potential Approach to Precision Medicine. Diabetes Care. 2022 Jan 1;45(1):204-212. doi: 10.2337/dc20-2806.

    PMID: 34716214DERIVED

  • McAlister FA, Zheng Y, Westerhout CM, Buse JB, Standl E, McGuire DK, Van de Werf F, Green JB, Armstrong PW, Holman RR; TECOS Study Group. Association between glycated haemoglobin levels and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease: a secondary analysis of the TECOS randomized clinical trial. Eur J Heart Fail. 2020 Nov;22(11):2026-2034. doi: 10.1002/ejhf.1958. Epub 2020 Jul 28.

    PMID: 32621557DERIVED

  • De Ferrari GM, Stevens SR, Ambrosio G, Leonardi S, Armstrong PW, Green JB, Wamil M, Holman RR, Peterson ED; TECOS Study Group. Low-density lipoprotein cholesterol treatment and outcomes in patients with type 2 diabetes and established cardiovascular disease: Insights from TECOS. Am Heart J. 2020 Feb;220:82-88. doi: 10.1016/j.ahj.2019.11.005. Epub 2019 Nov 13.

    PMID: 31790905DERIVED

  • Shavadia JS, Zheng Y, Green JB, Armstrong PW, Westerhout CM, McGuire DK, Cornel JH, Holman RR, Peterson ED. Associations between beta-blocker therapy and cardiovascular outcomes in patients with diabetes and established cardiovascular disease. Am Heart J. 2019 Dec;218:92-99. doi: 10.1016/j.ahj.2019.09.013. Epub 2019 Oct 20.

    PMID: 31715435DERIVED

  • Nauck MA, McGuire DK, Pieper KS, Lokhnygina Y, Strandberg TE, Riefflin A, Delibasi T, Peterson ED, White HD, Scott R, Holman RR. Sitagliptin does not reduce the risk of cardiovascular death or hospitalization for heart failure following myocardial infarction in patients with diabetes: observations from TECOS. Cardiovasc Diabetol. 2019 Sep 3;18(1):116. doi: 10.1186/s12933-019-0921-2.

    PMID: 31481069DERIVED

  • Guimaraes PO, Peterson ED, Stevens SR, Lokhnygina Y, Green JB, McGuire DK, Holman RR, Lopes RD. Antithrombotic treatment gap among patients with atrial fibrillation and type 2 diabetes. Int J Cardiol. 2019 Aug 15;289:58-62. doi: 10.1016/j.ijcard.2019.04.085. Epub 2019 Apr 30.

    PMID: 31079973DERIVED

  • Reed SD, Li Y, Leal J, Radican L, Adler AI, Alfredsson J, Buse JB, Green JB, Kaufman KD, Riefflin A, Van de Werf F, Peterson ED, Gray AM, Holman RR; TECOS Study Group. Longitudinal medical resources and costs among type 2 diabetes patients participating in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Diabetes Obes Metab. 2018 Jul;20(7):1732-1739. doi: 10.1111/dom.13292. Epub 2018 Apr 20.

    PMID: 29573215DERIVED

  • Standl E, Stevens SR, Armstrong PW, Buse JB, Chan JCN, Green JB, Lachin JM, Scheen A, Travert F, Van de Werf F, Peterson ED, Holman RR; TECOS Study Group. Increased Risk of Severe Hypoglycemic Events Before and After Cardiovascular Outcomes in TECOS Suggests an At-Risk Type 2 Diabetes Frail Patient Phenotype. Diabetes Care. 2018 Mar;41(3):596-603. doi: 10.2337/dc17-1778. Epub 2018 Jan 8.

    PMID: 29311155DERIVED

  • Sharma A, Green JB, Dunning A, Lokhnygina Y, Al-Khatib SM, Lopes RD, Buse JB, Lachin JM, Van de Werf F, Armstrong PW, Kaufman KD, Standl E, Chan JCN, Distiller LA, Scott R, Peterson ED, Holman RR; TECOS Study Group. Causes of Death in a Contemporary Cohort of Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: Insights From the TECOS Trial. Diabetes Care. 2017 Dec;40(12):1763-1770. doi: 10.2337/dc17-1091. Epub 2017 Oct 6.

    PMID: 28986504DERIVED

  • Pagidipati NJ, Navar AM, Pieper KS, Green JB, Bethel MA, Armstrong PW, Josse RG, McGuire DK, Lokhnygina Y, Cornel JH, Halvorsen S, Strandberg TE, Delibasi T, Holman RR, Peterson ED; TECOS Study Group. Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus: International Insights From the TECOS Trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Circulation. 2017 Sep 26;136(13):1193-1203. doi: 10.1161/CIRCULATIONAHA.117.027252. Epub 2017 Jun 16.

    PMID: 28626088DERIVED

  • Bethel MA, Engel SS, Green JB, Huang Z, Josse RG, Kaufman KD, Standl E, Suryawanshi S, Van de Werf F, McGuire DK, Peterson ED, Holman RR; TECOS Study Group. Assessing the Safety of Sitagliptin in Older Participants in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Diabetes Care. 2017 Apr;40(4):494-501. doi: 10.2337/dc16-1135. Epub 2017 Jan 5.

    PMID: 28057693DERIVED

  • Cornel JH, Bakris GL, Stevens SR, Alvarsson M, Bax WA, Chuang LM, Engel SS, Lopes RD, McGuire DK, Riefflin A, Rodbard HW, Sinay I, Tankova T, Wainstein J, Peterson ED, Holman RR; TECOS Study Group. Effect of Sitagliptin on Kidney Function and Respective Cardiovascular Outcomes in Type 2 Diabetes: Outcomes From TECOS. Diabetes Care. 2016 Dec;39(12):2304-2310. doi: 10.2337/dc16-1415. Epub 2016 Oct 14.

    PMID: 27742728DERIVED

  • Buse JB, Bethel MA, Green JB, Stevens SR, Lokhnygina Y, Aschner P, Grado CR, Tankova T, Wainstein J, Josse R, Lachin JM, Engel SS, Patel K, Peterson ED, Holman RR; TECOS Study Group. Pancreatic Safety of Sitagliptin in the TECOS Study. Diabetes Care. 2017 Feb;40(2):164-170. doi: 10.2337/dc15-2780. Epub 2016 Sep 14.

    PMID: 27630212DERIVED

  • McGuire DK, Van de Werf F, Armstrong PW, Standl E, Koglin J, Green JB, Bethel MA, Cornel JH, Lopes RD, Halvorsen S, Ambrosio G, Buse JB, Josse RG, Lachin JM, Pencina MJ, Garg J, Lokhnygina Y, Holman RR, Peterson ED; Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS) Study Group. Association Between Sitagliptin Use and Heart Failure Hospitalization and Related Outcomes in Type 2 Diabetes Mellitus: Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2016 May 1;1(2):126-35. doi: 10.1001/jamacardio.2016.0103.

    PMID: 27437883DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

TriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrazines

Results Point of Contact

Title
Senior Vice President, Global Clinical Development
Organization
Merck Sharp & Dohme Corp.
ClinicalTrialsDisclosure@merck.com
1-800-672-6372

Study Officials

  • Medical Director

    Merck Sharp & Dohme LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 11, 2008

First Posted

November 13, 2008

Study Start

December 10, 2008

Primary Completion

March 30, 2015

Study Completion

March 30, 2015

Last Updated

November 23, 2021

Results First Posted

April 15, 2016

Record last verified: 2021-10

Data Sharing

IPD Sharing
Will share

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

More information