scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Sitagliptin and TECOS

2020 ◽  
Vol 20 (1) ◽  
pp. 55-57
Author(s):  
Miles Fisher
Keyword(s):  
Unstable Angina ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Cardiovascular Outcome ◽  
Clinical Role ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Major Cardiovascular Events ◽  
Cardiovascular Outcome Trial ◽  
Outcome Trial

TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin) was an investigator-initiated cardiovascular outcome trial with sitagliptin. It compared sitagliptin and placebo in 14,671 subjects with type 2 diabetes and demonstrated non-inferiority for major cardiovascular events plus hospitalisation for unstable angina (cardiovascular death, myocardial infarction, stroke, unstable angina) but not superiority. Rates of hospitalisation for heart failure did not differ between the sitagliptin and placebo groups, and there were no significant between-group differences in rates of acute pancreatitis or pancreatic cancer. The clinical role for dipeptidyl peptidase-4 (DPP-4) inhibitors is diminishing as they have not been demonstrated to reduce cardiovascular events and are not associated with weight reduction, but if a DPP-4 inhibitor is indicated, the results of TECOS show that sitagliptin appears safer than saxagliptin or alogliptin.

scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Liraglutide and LEADER

2020 ◽  
Vol 20 (2) ◽  
pp. 142-144
Author(s):  
Miles Fisher
Keyword(s):  
Heart Failure ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Cardiovascular Outcome ◽  
Secondary Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Outcome Trials ◽  
Major Cardiovascular Events ◽  
Cardiovascular Outcome Trial ◽  
Outcome Trial

LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) was an FDA-mandated cardiovascular outcome trial with liraglutide and was the first trial with a glucagon-like peptide-1 (GLP-1) receptor agonist to demonstrate a significant reduction in cardiovascular events. It compared liraglutide and placebo in 9,340 people with type 2 diabetes and either existing cardiovascular disease or age >60 years with at least one cardiovascular risk factor. LEADER demonstrated superiority for major cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), and cardiovascular deaths were significantly reduced, as was all-cause mortality. Hospitalisation for heart failure, which was a secondary outcome, was not significantly reduced. Compared with the EMPA-REG OUTCOME trial, the curves for major adverse cardiovascular events in LEADER separated later, and the absence of a clear effect on hospitalisation for heart failure or on estimated glomerular filtration rate suggests that the mechanism of cardiovascular benefit for liraglutide was different from that for empagliflozin

scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Alogliptin and EXAMINE

2019 ◽  
Vol 19 (2) ◽  
pp. 133-135
Author(s):  
Miles Fisher
Keyword(s):  
Heart Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcome ◽  
Cardiovascular Outcome Trials ◽  
Coronary Syndrome ◽  
Major Cardiovascular Events ◽  
Cardiovascular Outcome Trial ◽  
Subsequent Publication ◽  
Outcome Trial

EXAMINE was an FDA mandated cardiovascular outcome trial with alogliptin. In contrast to other cardiovascular outcome trials with DPP-4 inhibitors, it was performed in subjects with a recent acute coronary syndrome. EXAMINE compared alogliptin and placebo in 5,380 subjects with type 2 diabetes and demonstrated non-inferiority for major cardiovascular events (cardiovascular death, myocardial infarction, stroke) but not superiority. Data on hospitalisation for heart failure were not included in the principal publication. A subsequent publication showed no overall increase in hospitalisation for heart failure with alogliptin, but when subjects with and without baseline heart failure were separated there was a significant increase in the group without heart failure at baseline. No clear clinical benefit has been established for alogliptin, and there are alternatives such as sitagliptin and linagliptin that are not associated with an increase in hospitalisation for heart failure.

scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Lixisenatide and ELIXA

2020 ◽  
Vol 20 (1) ◽  
pp. 52-54
Author(s):  
Miles Fisher
Keyword(s):  
Myocardial Infarction ◽  
Unstable Angina ◽  
Cardiovascular Events ◽  
Cardiovascular Outcome ◽  
Secondary Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Outcome Trials ◽  
Receptor Agonists ◽  
Coronary Syndrome ◽  
Cardiovascular Outcome Trial

ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) was an FDA mandated cardiovascular outcome trial with lixisenatide. In contrast to later cardiovascular outcome trials with glucagon-like peptide-1 (GLP-1) receptor agonists, it was performed in subjects with a recent myocardial infarction or hospitalisation for unstable angina within the previous 180 days. ELIXA compared lixisenatide and placebo in 6,068 subjects with type 2 diabetes and demonstrated non-inferiority for major cardiovascular events plus unstable angina (cardiovascular death, myocardial infarction, stroke, unstable angina) but not superiority. Similarly, there was no difference in hospitalisation for heart failure which was a secondary outcome. A subsequent exploratory analysis showed that lixisenatide reduced progression of the urinary albumin to creatinine ratio in patients with macroalbuminuria, and was associated with a lower risk of new-onset macroalbuminuria. No clear clinical benefit has been established for lixisenatide, and there are alternative GLP-1 receptor agonists such as liraglutide, semaglutide and dulaglutide that are associated with a reduction in major adverse cardiovascular events.

scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Saxagliptin and SAVOR-TIMI 53

2019 ◽  
Vol 19 (1) ◽  
pp. 34-36
Author(s):  
Miles Fisher
Keyword(s):  
Heart Failure ◽  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Cardiovascular Outcome ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Increased Risk ◽  
Cardiovascular Outcome Trial

SAVOR-TIMI 53 was the first FDA-mandated cardiovascular outcome trial to be presented and published. It compared saxagliptin and placebo in 16,492 patients with type 2 diabetes. SAVOR-TIMI 53 demonstrated non-inferiority for major cardiovascular events (cardiovascular death, myocardial infarction, stroke) but not superiority. An unexpected statistically significant increase in adjudicated hospitalisation for heart failure was seen in the saxagliptin group. Post hoc analysis demonstrated that subjects at greatest risk for hospitalisation for heart failure had previous heart failure, an estimated glomerular filtration rate <60 mL/min, or elevated baseline levels of N-terminal pro-B type natriuretic peptide. As other dipeptidyl peptidase 4 (DPP-4) inhibitors are available which have not been associated with an increased risk of hospitalisation for heart failure, saxagliptin should be avoided in patients with heart failure or a reduced estimated glomerular filtration rate.

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