The design and rationale of the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus–Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 Study

• Published in: The American heart journal Vol. 162; no. 5; pp. 818 - 825.e6
• Main Authors: Scirica, Benjamin M., Bhatt, Deepak L., Braunwald, Eugene, Steg, Ph. Gabriel, Davidson, Jaime, Hirshberg, Boaz, Ohman, Peter, Price, Deborah L., Chen, Roland, Udell, Jacob, Raz, Itamar
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2011; Mosby; Elsevier Limited
• Subjects: Adamantane - administration & dosage; Adamantane - analogs & derivatives; Adamantane - therapeutic use; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular; Clinical trials; Coronary heart disease; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Dipeptides - administration & dosage; Dipeptides - therapeutic use; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Disease; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzymes; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; France; Glucose; Heart; Humans; Israel; Male; Medical sciences; Middle Aged; Mortality; Myocardial Infarction - complications; Myocardial Infarction - mortality; Myocarditis. Cardiomyopathies; Polypeptides; Regulatory approval; Research Design; Risk factors; Studies; Survival Analysis; Treatment Outcome; United States; France; United States; Israel; Endocrinopathy; Human; Myocardial infarction; Prognosis; Diabetes mellitus; Patient; Cardiovascular disease; Coronary heart disease; Myocardial disease; Fibrinolysis; Design; Blood vessel; Circulatory system; Cardiology; Saxagliptin
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2011.08.006

Saxagliptin, a dipeptidyl peptidase 4 inhibitor, improves glycemic control in patients with type 2 diabetes mellitus (T2DM) by increasing endogenous active, intact glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide in response to food, which augments insulin secretion and decreases glucagon release. SAVOR-TIMI 53 is a phase 4, randomized, double-blind, placebo-controlled trial conducted in 25 countries that is designed to evaluate the safety and efficacy of saxagliptin during long-term treatment of approximately 16,500 patients with T2DM. Eligible patients who are either treatment naive or on any background antidiabetic treatment (except incretin therapy) with history of established cardiovascular (CV) disease or multiple risk factors are randomized 1:1 to saxagliptin 5 mg QD (2.5 mg in subjects with moderate/severe renal impairment) or matching placebo, stratified by qualifying disease state. The primary end point is the composite of CV death, nonfatal myocardial infarction, or nonfatal ischemic stroke. The trial will continue until approximately 1,040 primary end points accrue, providing 85% power to identify a 17% relative reduction of the primary end point with saxagliptin versus placebo and 98% power to test for noninferiority of saxagliptin versus placebo (reject the upper limit of 95% CI for a hazard ratio <1.3 at a 1-sided α of .025). SAVOR-TIMI 53 is testing the hypothesis that treatment with saxagliptin is safe and reduces CV events in high-risk patients with T2DM.