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 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 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 Canagliflozin and the CANVAS Program, dapagliflozin and DECLARE-TIMI 58, ertugliflozin and VERTIS CV

2021 ◽  
Author(s):  
Miles Fisher
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Death ◽  
Cardiovascular Outcome ◽  
Integrated Analysis ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cardiovascular Outcome Trials ◽  
Significant Difference

EMPA-REG OUTCOME was a landmark trial with the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, which demonstrated significant reductions in major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) driven by reductions in cardiovascular deaths and accompanied by an early reduction in hospitalisation for heart failure. This was followed by cardiovascular outcome trials with canagliflozin, dapagliflozin and ertugliflozin. The CANVAS Program was an integrated analysis of the CANVAS and CANVAS-R trials with canagliflozin. It demonstrated a significant reduction in MACE, but not in any of the components, and there was an unexpected increase in amputations and fractures with canagliflozin. The DECLARE-TIMI 58 trial with dapagliflozin had two co-primary endpoints. A composite endpoint of cardiovascular death or hospitalisation for heart failure was significantly reduced, but there was no significant difference in MACE comparing dapagliflozin with placebo. Analysis of patients with a prior myocardial infarction, however, demonstrated significant reductions in MACE. The VERTIS CV trial with ertugliflozin was disappointing as there was no difference in MACE comparing ertugliflozin and placebo. In all four trials a reduction in hospitalisation for heart failure was observed in patients with type 2 diabetes, regardless of whether they had existing atherosclerotic cardiovascular disease or increased cardiovascular risk. Pre-specified renal outcomes were reduced with empagliflozin, canagliflozin and dapagliflozin, and these drugs are now commonly used in the management of people with type 2 diabetes. It is hard to envisage an ongoing role for ertugliflozin in routine clinical management as the evidence for its cardiovascular benefit is not convincing.

scholarly journals Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA®)

2015 ◽  
Vol 12 (3) ◽  
pp. 164-174 ◽  
Author(s):  
Nikolaus Marx ◽  
Julio Rosenstock ◽  
Steven E Kahn ◽  
Bernard Zinman ◽  
John J Kastelein ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Outcome ◽  
Cardiovascular Outcome Trial ◽  
Outcome Trial ◽  
Baseline Characteristics

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.

scholarly journals Prevalent and Incident Heart Failure in Cardiovascular Outcome Trials of Patients With Type 2 Diabetes

2018 ◽  
Vol 71 (12) ◽  
pp. 1379-1390 ◽  
Author(s):  
Stephen J. Greene ◽  
Muthiah Vaduganathan ◽  
Muhammad Shahzeb Khan ◽  
George L. Bakris ◽  
Matthew R. Weir ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Outcome ◽  
Cardiovascular Outcome Trials ◽  
Incident Heart Failure
Sign in / Sign up

Export Citation Format

Share Document