Article

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

Division of Endocrinology, Duke University Medical Center, Durham NC.
American heart journal (Impact Factor: 4.56). 12/2013; 166(6):983-989.e7. DOI: 10.1016/j.ahj.2013.09.003
Source: PubMed

ABSTRACT Sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, lowers blood glucose when administered as monotherapy or in combination with other antihyperglycemic agents. TECOS will evaluate the effects of adding sitagliptin to usual diabetes care on cardiovascular outcomes and clinical safety. TECOS is a pragmatic, academically run, multinational, randomized, double-blind, placebo-controlled, event-driven trial recruiting approximately 14,000 patients in 38 countries who have type 2 diabetes (T2DM), are at least 50 years old, have cardiovascular disease, and have an hemoglobin A1c value between 6.5% and 8.0%. Eligible participants will be receiving stable mono- or dual therapy with metformin, sulfonylurea, or pioglitazone, or insulin alone or in combination with metformin. Randomization is 1:1 to double-blind sitagliptin or matching placebo, in addition to existing therapy in a usual care setting. Follow-up occurs at 4-month intervals in year 1 and then twice yearly until 1300 confirmed primary end points have occurred. Glycemic equipoise between randomized groups is a desired aim. The primary composite cardiovascular endpoint is time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina, with cardiovascular events adjudicated by an independent committee blinded to study therapy. TECOS is a pragmatic-design cardiovascular outcome trial assessing the cardiovascular effects of sitagliptin when added to usual T2DM management.

1 Follower
 · 
209 Views
  • Source
    • "Because of the controversy of cardiovascular effects of sitagliptin and also other DPP-4 inhibitors, further studies are required especially in patients with CKD to stratify the risk–benefit effect. Therefore, the TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin), a randomized , double-blind trial is essential for further evaluation for the safety of this drug [27]. This trial enrolled patients with established cardiovascular diseases; however, the trial excluded patients who had an eGFR of b30 ml/min/1.73 "
  • Source
    • "Because of the controversy of cardiovascular effects of sitagliptin and also other DPP-4 inhibitors, further studies are required especially in patients with CKD to stratify the risk–benefit effect. Therefore, the TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin), a randomized , double-blind trial is essential for further evaluation for the safety of this drug [27]. This trial enrolled patients with established cardiovascular diseases; however, the trial excluded patients who had an eGFR of b30 ml/min/1.73 "
    [Show abstract] [Hide abstract]
    ABSTRACT: The cardiovascular safety and efficacy of sitagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, in type 2 diabetic patients with chronic kidney disease (CKD) after acute myocardial infarction (AMI) are unclear. We analyzed data from the Taiwan National Health Insurance Research Database between March 1st, 2009 and December 31st, 2011. A total of 1025 AMI patients with diabetes with chronic kidney disease were selected as the study cohort. The study evaluated the cardiovascular safety and efficacy of sitagliptin by comparing 205 subjects (20%) who use sitagliptin to 820 matched subjects (80%) who do not. The primary outcomes included myocardial infarction, ischemic stroke or cardiovascular death. Primary composite outcomes occurred in 54 patients in the sitagliptin group (26.3%) and in 164 patients in the comparison group (20.0%) (HR, 1.32; 95% CI, 0.97-1.79; P=0.079) during the mean follow-up of 1.02years (SD=0.71years). The sitagliptin group had similar risks of ischemic stroke, all-cause mortality or hospitalization for heart failure (HF) compared to the non-sitagliptin group (P=0.938, 0.523 and 0.795 respectively). However, sitagliptin use was associated with increased risks of recurrent myocardial infarction (HR, 1.73; 95% CI, 1.15-2.58; P=0.008) and percutaneous coronary revascularization (HR, 1.43; 95% CI, 1.04-1.95; P=0.026). Among type 2 diabetic patients with CKD after AMI, the use of sitagliptin was not associated with an increased risk of cardiovascular death, ischemic stroke or hospitalization for HF but was associated with increased risks of recurrent MI and percutaneous coronary revascularization. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    International Journal of Cardiology 12/2014; 181C:200-206. DOI:10.1016/j.ijcard.2014.12.029 · 6.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to achieve glycemic targets in patients with type 2 diabetes mellitus (T2DM). The addition of DPP-4 inhibitors to ongoing insulin therapy is expected to reduce insulin dosage, leading to a reduction in the frequency of hypoglycaemia and/or weight gain. Recent studies have demonstrated potential anti-atherosclerotic effects for DPP-4 inhibitors. The aim of the present ongoing study is to assess the effects of sitagliptin on the progression of atherosclerosis in patients with insulin-treated T2DM using carotid intima-media thickness (IMT), an established marker of cardiovascular disease.Methods and Design: The Sitagliptin Preventive study of Intima media thickness Evaluation (SPIKE) is a prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study. Between February 2012 and September 2012, 282 participants who failed to achieve glycemic control despite insulin therapy were recruited at 12 clinics and randomly allocated to the sitagliptin group (n = 142) or the control group (n = 140). Primary outcomes are changes in maximum and mean IMT of the common carotid artery after 24-month treatment period measured by carotid arterial echography. Secondary outcomes include changes in glycemic control, parameters related to beta-cell function and diabetic nephropathy, occurrence of cardiovascular events and adverse events such as hypoglycaemia, and biochemical markers of vascular function. The present study is designed to assess the effects of sitagliptin on the progression of carotid IMT. Results will be available in the near future, and the findings are expected to provide new strategy to prevent atherosclerosis in patients with insulin-treated T2DM.Clinical Trial Registration: UMIN000007396.
    Diabetology and Metabolic Syndrome 03/2014; 6(1):35. DOI:10.1186/1758-5996-6-35 · 2.50 Impact Factor