On behalf of the savortimi 53 steering committee and investigators. Frequency of cancer events with saxagliptin in the savor. Pdf saxagliptin and cardiovascular outcomes in patients with. Saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus savor timi 53. The saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus thrombolysis in myocardial infarction 53 savortimi 53 trial randomized 16,492 patients with type 2 diabetes t2d with high cv risk and varying degrees of renal function and albuminuria to treatment with the dpp4 inhibitor saxagliptin or placebo. Associations between metformin exposure and outcomes were estimated with. The saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus savor thrombolysis in myocardial infarction timi 53 trial randomized 16,492 patients with t2dm who were at risk for cv events to receive saxagliptin or placebo for a median period of 2 years. Cebrian cuenca and others published saxagliptin and heart failure in the savor timi 53 trial. Savor timi 53 saxagliptin and cardiovascular outcomes in. Efficacy and safety of saxagliptin in older participants. Objective to examine the safety and cardiovascular cv effects of saxagliptin in the predefined elderly. Pdf heart failure, saxagliptin, and diabetes mellitus. Savortimi 53 finds no increase or decrease in ischemic.
Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus savor timi 53 trial 1. Publications home of jama and the specialty journals of the. The saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus savor thrombolysis in myocardial infarction timi 53 savor timi 53 trial, reported by scirica et. The saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitusthrombolysis in myocardial infarction 53 savor timi 53 trial randomized 16,492 patients with type 2 diabetes t2d with high cv risk and varying degrees of renal function and albuminuria to treatment with the dpp4 inhibitor saxagliptin or placebo. The warnings are based on the fdas evaluation of two large clinical trials of these agents in patients with heart disease. It compared saxagliptin and placebo in 16,492 patients with type 2 diabetes. Cardiovascular outcomes trials in patients with diabetes. Hypoglycaemic events were a prespecified outcome in the study and were defined as a symptomatic episode that recovered with carbohydrates or any recorded blood glucose saxagliptin, and diabetes mellitus. Savortimi 53 evaluated drug intervention saxagliptin onglyza vs. A therapy based on the incretins, which represents a significant qualitative progress, is close to an ideal. Saxagliptin cardiovascularoutcomes saxagliptin cardiovascularoutcomes in patients with type 2 diabetes mellitus.
However, few diabetes mellitus trials have prospectively evaluated and adjudicated heart failure as an end point. The design and rationale of the saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitusthrombolysis in myocardial infarction savor timi 53 study. Cardiovascular outcomes of patients in savortimi 53 by baseline. In the cdm, the risk equations re to predict the risk of macrovascular complications are informed by risk factor progression values. On behalf of the savor timi 53 steering committee and investigators. Cardiovascular outcomes of patients in savortimi 53 by. Research design and methods savor timi 53 was a multicenter, ran. Saxagliptin, alogliptin, and cardiovascular outcomes nejm. Neither the reason why only saxagliptin among several dipeptidyl peptidase4 dpp4 inhibitors increased the risk, nor the clinical implication of the result has been explained. The type 2 diabetes mellitus treatment is currently effective but still not ideal. Savortimi 53 raises bar for cv outcome trials in diabetes. Saxagliptin and heart failure in the savortimi 53 trial. Bhatt, md, mphon behalf of the savortimi 53 steering committee and investigators.
Impact of treatment with saxagliptin on glycaemic stability. Pdf saxagliptin and cardiovascular outcomes in patients. However, saxagliptin increased the risk of hypoglycaemia and may also have increased the risk of admission to hospital because of heart failure n16492, median follow up 2. Effect of saxagliptin on renal outcomes in the savortimi.
Reductions in blood glucose were also greater with saxagliptin, with mean reductions in hba1c of 0. Saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus savor timi 53 deepak l. Regardless, the savor timi 53 trial met the primary safety objective demonstrating no increased risk of cardiovascular death, myocardial infarction, or ischemic stroke with saxagliptin. Saxagliptin and heart failure in the savor timi 53 trial. Savor timi 53 demonstrated noninferiority for major cardiovascular events cardiovascular death, myocardial infarction, stroke but not superiority. Results of savortimi 53 interview with benjamin scirica, md, mph, assistant professor of medicine, harvard medical school, boston, ma a large trial of the dipeptidyl peptidase4 dpp4 inhibitor saxagliptin examined cardiovascular safety. Reflections on the bradford hill criteria find, read and cite all the. Savor timi 53 was a multicenter, randomized, doubleblind, placebocontrolled, phase 4 trial. Astrazeneca and bristolmyers squibb announce top line. Oct 28, 2014 heart failure, saxagliptin, and diabetes mellitus. Timi 53 saxagliptin, examine alogliptin, tecos sitagliptin, carmelina linagliptin, carolina linagliptin, elixa lixisenatide, leader liraglutide, exscel exenatide once. Saxagliptin is a dipeptidyl peptidase4 dpp4 inhibitor approved in the us, canada, europe, and. United kingdom prospective diabetes study ukpds 68 15, ukpds 82 20, advance 21, swedish.
In the saxaglipitin assessment of vascular outcomes recorded in patients with diabetes mellitusthrombolysis in myocardial infarction 53 savor timi 53 trial, noninferiority to placebo in terms of cardiovascular safety among highrisk patients was demonstrated. The saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus savor thrombolysis in myocardial infarction timi 53 trial randomized trial of 16 492 patients placebo, n 8212. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes and moderate or severe renal impairment. Clinical effectiveness, cost and safety comparisons not to. Saxagliptin hydrochloride monograph for professionals. Savor timi 53 study reported that adding saxagliptin to other bloodglucoselowering medication did not reduce the risk of cv events or some renal outcomes. Use of sodiumglucose cotransporter 2 inhibitors and risk. Savortimi 53 sets new standard for cardiovascular outcome.
Saxagliptin and cardiovascular outcomes in patients with type. Savor timi 53 was a doubleblind, placebocontrolled trial that randomized patients with type 2 diabetes to either saxagliptin or placebo while all other diet and lifestyle modifications, background antihyperglycemic therapies except incretinbased therapies, and cardiovascular therapies were left to the discretion of the treating provider. Savor timi 53 was the first fdamandated cardiovascular outcome trial to be presented and published. Savor timi 53 saxagliptin 16,492 pts w cv disease or mult risk factors. In this study of adult patients with type 2 diabetes with either a. Rxfiles trial summary oct 20 kellie towriss bsp, hosp pharm resident. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. Savor timi 53 steering committee and investigators, scirica b. Cardiovascular outcomes according to urinary albumin and. Methods we randomized 16 492 patients with type 2 diabetes t2d to saxagliptin or placebo, added to current antidiabetic medications, and followed them for a median of 2. Diabetes mellitus and heart failure frequently coexist.
Effect of saxagliptin on renal outcomes in the savor timi 53. Top line results of a large phase 4 study with saxagliptin onglyza, bristolmyers squibb and astrazeneca demonstrate that the drug is safe but has no. Effect of saxagliptin on renal outcome request pdf. Since 2008, the data from various cardiovascular outcome trials have been reported, including savor. The saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus thrombolysis in myocardial infarction 53 savor timi 53 trial randomized 16,492 patients with type 2 diabetes t2d with high cv risk and varying degrees of renal function and albuminuria to treatment with the dpp4 inhibitor saxagliptin or placebo. Saxagliptin is a selective dipeptidyl peptidase4 dpp4 inhibitor. The saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitusthrombolysis in myocardial infarction 53 savortimi 53 trial randomized 16,492 patients with type 2 diabetes t2d with high cv risk and varying degrees of renal function and albuminuria to treatment with the dpp4 inhibitor saxagliptin or placebo.
Number and % of patients at the saxagliptin and placebo arms, according to egfr and on treatment acr groups at baseline, 1 year, and eot n % from acr by treatment arm egfr50 mlminbsa acr 300 mgg mgg saxagliptin. Metformin use and clinical outcomes among patients with. Savor timi 53 steering committee and investigators. In the trial as a whole, saxagliptin had no detectable. Comparison of new glucoselowering drugs on risk of heart. In the saxaglipitin assessment of vascular outcomes recorded in patients with diabetes mellitusthrombolysis in myocardial infarction 53 savortimi 53 trial, noninferiority to placebo in terms of cardiovascular safety among highrisk patients was demonstrated.
Pdf saxagliptin and heart failure in the savortimi 53. The savor timi 53 trial was randomized and placebocontrolled, and looked at 16,492 patients for a median of 2. We thank drs muskiet, tonneijck, and van raalte for calling attention to the potentially detrimental consequences of simultaneous inhibition of dipeptidyl peptidase 4 and angiotensinconverting enzyme ace. The savor timi 53 trial supports the overall cv safety of saxagliptin in a robust number of elderly and very elderly participants, although the risk of heart failure hospitalization was increased. Saxagliptin, alogliptin show cardiovascular safety in. A total of 16 492 patients with type 2 diabetes mellitus and a history of, or at. Costeffectiveness analysis of empagliflozin in comparison to. Sitagliptin use was not associated with increased weight in tecos efigure 1d in the supplement, with similar neutral weight effects of saxagliptin and alogliptin in the savor timi 53 and examine trials, respectively. We randomized 16 492 patients with type 2 diabetes t2d to saxagliptin or placebo, added to current antidiabetic medications, and followed them for. Assessment of the risk of hospitalization for heart. Bhatt, md, mph on behalf of the savortimi 53 steering committee and investigators european society of cardiology, amsterdam september 2, 20. Saxagliptin and cardiovascular cv outcomes in patients with type 2 diabetes mellitus. Saxagliptin and cardiovascular outcomes in patients with.
To study the effects of saxagliptin, a dipeptidyl peptidase. European society of cardiology,amsterdam september 2, 20. Savor timi 53 saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitusthrombolysis in myocardial infarction 53 randomized 16,492 patients with type 2 diabetes and a history of established cardiovascular disease or multiple risk factors for vascular disease to either saxagliptin, doses ranging from 2. The results of the savor timi 53 trial indicate that saxagliptin, a dpp4 inhibitor, is not associated with an excess of cv events as compared with placebo in patients with dm2 and either established cv disease or risk factors. Saxagliptin statistically significantly increased the risk of hospitalization for heart failure compared with placebo in the clinical trial of savor timi 53. The design, baseline patient characteristics, and primary results of the savor timi 53 trial nct01107886 have been reported previously. Scirica bm1, braunwald e2, raz i2, cavender ma2, morrow da2, jarolim p2, udell ja2, mosenzon o2, im k2, umezeronini aa2, pollack ps2, hirshberg b2, frederich r2, lewis bs2, mcguire dk2, davidson j2, steg pg2. The saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus savor timi 53 trial was a large international clinical trial that randomized patients to the diabetes drug saxagliptin onglyza, a selective dipeptidyl peptidase 4 dpp4 inhibitor, or to placebo in order to determine the effect on heart attack risk. Saxagliptin assessment of vascular outcomes recorded in. Timi 53 cv outcomes trial summary saxagliptin and cardiovascular cv outcomes in patients with type 2 diabetes mellitus. Effect of saxagliptin on renal outcomes in the savor timi 53 study appendixes. These data provide additional information when considering newer antihyperglycemic agents in patients at high risk of cardiovascular events.
Savor timi 53 saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. The saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus savorthrombolysis in myocardial infarction timi 53 trial randomized trial of 16 492 patients placebo, n 8212. In this post hoc analysis, patients in savor timi 53 saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus with baseline biomarker samples n12 156 were classified as ever versus never taking metformin during the trial period. No cancer signal with saxagliptin at 2 years in savortimi 53. Thrombolysis in myocardial infarction 53 savor timi 53 trial randomized 16,492 type 2 diabetic patients with high cv risk and varying degrees of renal function and albuminuria to treatment with the dpp4 inhibitor saxagliptin or placebo and followed them prospectively for a median of 2. Savortimi 53 is a randomized, doubleblind, placebocontrolled trial to assess the cardiovascular efficacy and safety of saxaglipitin, a dpp4 inhibitor, when added to standard of care in patients with type 2 diabetes mellitus. European society of cardiology, amsterdam september 2, 20. Observations from the savortimi 53 randomized trial. Savor timi 53 saxagliptin and cardiovascular outcomes. Effect of saxagliptin on renal outcomes in the savor timi53 study appendixes.
Response to letter regarding article, heart failure. Saxagliptin and cancer in the savortimi 53 trial request pdf. Assessment of the risk of hospitalization for heart failure. No cancer signal with saxagliptin at 2 years in savortimi 53 medscape jun 06, 2015. Savor timi 53 is part of an esc hotline session dedicated to risk factors and diabetes. Thrombolysis in myocardial infarction timi 53 trial. Effect of saxagliptin on renal outcomes in the savor timi. Effect of saxagliptin on renal outcomes in the savortimi 53. The savor timi 53 trial supports the overall cv safety of saxagliptin in a robust number of elderly and very elderly participants, although the risk of heart failure hospitalization was increased irrespective of age category. Saxagliptin and cardiovascular outcomes in patients with type 2.
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