Health Condition 1: null- Type 2 Diabetes Mellitus with pre existing documented vascular disease in the coronary, cerebral or peripheral arteries. Health Condition 2: E119- Type 2 diabetes mellitus without complications
Conditions
Interventions
Intervention1: The recommended dose of Sitagliptin is 100 mg once daily as monotherapy or as combination therapy with metformin, a sulfonylurea, a PPARy agonist (i.e., thiazolidinediones), or metformi
80 mL/min/1.73 m2). For patients with moderately decreased renal filtration (i.e., estimated GFR of 30 to 50 mL/min/1.73 m2), the plasma levels of sitagliptin are approximately 2-fold higher than tho
see Section 5.1)
if the eGFR drops to 30 mL/min/1.73 m2, the sitagliptin dose will be reduced to 25 mg q.d. As this is a placebo controlled trial there is no comparator agent.
Control Intervention1: placebo: Matching
Sponsors
Duke Clinical Research Institute
Merck Co Inc
Eligibility
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria to participate in the study: a) Patient has T2DM and has not previously required insulin other than for a short term, reversible illness (less than three consecutive months of insulin use), or during pregnancy. b) Patient is able to see a usual care provider at least twice a year c) Patient is receiving metformin, pioglitazone, or a sulfonylurea as monotherapy or any dual combination of metformin, pioglitazone, or a sulfonylurea continuously for at least 3 months without dose alterations, and has an HbA1c of ≥ 6.5% and ≤ 8.0% (HbA1c must be documented within 3 months prior to study enrollment). Patients whose HbA1c is 8.0% may, at the discretion of the investigator, have their oral AHA therapy adjusted and be re-screened for randomization eligibility (HbA1c of ≥ 6.5% and ≤ 8.0%) following a 3-month period on a stable AHA dose. d) Patient is ≥ 50 years of age with preexisting vascular disease, defined as having any one of the following: i) History of a major clinical manifestation of coronary artery disease (i.e., myocardial infarction, surgical or percutaneous [balloon and/or stent] coronary revascularization procedure, or coronary angiography showing at least one stenosis ≥ 50% in a major epicardial artery or branch vessel); ii) Ischemic cerebrovascular disease, including: ? History of ischemic stroke. Strokes not known to be hemorrhagic will be allowed as part of this criterion; ? History of carotid arterial disease as documented by ≥ 50 % stenosis documented by carotid ultrasound, magnetic resonance imaging (MRI), or angiography, with or without symptoms of neurologic deficit. ? Atherosclerotic peripheral arterial disease, as documented by objective evidence such as amputation due to vascular disease, current symptoms of intermittent claudication confirmed by an ankle-brachial pressure index or toe brachial pressure index less than 0.9 or history of surgical or percutaneous revascularization procedure. e) Female patients agree to use an effective method of contraception or must not otherwise be at risk of becoming pregnant. f) Patient understands the study procedures, alternative treatments available, and the risks involved with the study, and voluntarily agrees to participate by providing written informed consent. g) Patient agrees to provide permission to obtain all medical records necessary for complete data ascertainment during the follow-up period.
Exclusion criteria
Exclusion criteria: Patient has a history of type 1 diabetes mellitus, a history of ketoacidosis, or is currently taking insulin. b) Patient has taken an approved or investigational DPP-4 inhibitor agent (e.g., sitagliptin, alogliptin, saxagliptin, or vildagliptin), GLP-1 analogues (e.g., exenatide, exenatide LAR, or liraglutide), or a thiazolidinedione other than pioglitazone within the past three months. c) Patient has cirrhosis of the liver, as assessed by medical history. d) Patient is enrolled in another experimental protocol which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial. e) Patient has a planned or anticipated revascularization procedure. f) Pregnancy or planned pregnancy during the trial period. g) Patient has medical history that indicates a life expectancy of < 2 years or might limit the individual?s ability to take trial treatments for the duration of the study. h) Patient has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose a risk to the patient, make participation not in the patient?s best interest, confound the results of the study (e.g., if patient cannot comply with requirements of the study), or interfere with the patient?s participation for the full duration of the study. i) Patient has an estimated GFR (calculated based on serum creatinine via the MDRD formula [10]) of < 30 mL/min/1.73 m2. j) Patient has a known allergy or intolerance to sitagliptin. k) Patient has previously been enrolled in this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to first confirmed CV event in the primary composite CV endpointTimepoint: Defined as the time from randomization to first confirmed event in the primary composite CV endpoint (CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization). | — |
Secondary
| Measure | Time frame |
|---|---|
| ? Time to first confirmed CV event in the secondary composite CV endpointTimepoint: defined as time from randomization to first confirmed event in the secondary composite CV endpoint (CV-related death, nonfatal MI, or nonfatal stroke).;Change from baseline in eGFR over timeTimepoint: Defined as change over time compared to baseline in the Estimated Glomerular Filteration Rate (eGFR) ;Change from baseline in HbA1c over timeTimepoint: Defined as change over time compared to baseline in the Hemoglobin A1c (HbA1c) ;Change from baseline in urinary albumin to creatinine ratio over timeTimepoint: Defined as change over time compared to baseline in the albumin to creatinine ratio ;Count of hospitalizations for any reasonTimepoint: Defined as number of hospitalization of the patients for any reason;Time to all-cause mortalityTimepoint: defined as time from randomization to death due to any cause.;Time to congestive heart failureTimepoint: defined as time from randomization to hospital admission for congestive heart failure and treatment with intravenous diuretics or inotropes.;Time to first confirmed CV event in the components of the primary composite endpointTimepoint: Defined as time from randomization to each of the components of the primary composite endpoint (CV-related death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization).;Time to initiation of chronic insulin therapyTimepoint: Defined as continuous use longer than three months;Time to initiation of first co-interventional agent (i.e., next oral AHA or chronic insulin therapyTimepoint: Defined as time required from baseline to initiate first co-interventional agent (i.e. next oral AHA or chronic insulin therapy) | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czech Republic, Estonia, Finland, France, Germany, Hungary, India, Israel, Italy, Latvia, Lithuania, Malaysia, Netherlands, New Zealand, Norway, Poland, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactDr Monisha Sharma
MSD Pharmaceuticals Pvt Ltd
Outcome results
None listed