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 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 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 Empagliflozin and EMPA-REG OUTCOME

2020 ◽  
Vol 20 (2) ◽  
pp. 138-141
Author(s):  
Miles Fisher
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Outcome ◽  
Secondary Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cardiovascular Outcome Trial

EMPA-REG OUTCOME was an FDA-mandated cardiovascular outcome trial with empagliflozin and was the first completed trial with a sodium-glucose co-transporter-2 (SGLT2) inhibitor. EMPA-REG OUTCOME compared empagliflozin and placebo in 7,020 subjects with type 2 diabetes and established atherosclerotic cardiovascular disease. The results were astounding as EMPA-REG OUTCOME demonstrated superiority for major cardiovascular events (cardiovascular death, myocardial infarction, stroke) and cardiovascular deaths were significantly reduced, as was all-cause mortality. Hospitalisation for heart failure, which was a secondary outcome, was also significantly reduced. Later trials with SGLT2 inhibitors have demonstrated reductions in major adverse cardiovascular events (MACE) and hospitalisation for heart failure, and trials with glucagon-like peptide 1 receptor agonists have demonstrated reductions in MACE. Collectively, these trials could transform the management of people with type 2 diabetes.

4113Glucose lowering drugs or strategies, major adverse cardiovascular events and heart failure outcomes, and association with weight loss - meta-analysis of large cardiovascular outcome trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O R Ghosh-Swaby ◽  
S G Goodman ◽  
L A Leiter ◽  
A Cheng ◽  
K Connelly ◽  
...  
Keyword(s):  
Heart Failure ◽  
Weight Loss ◽  
Risk Reduction ◽  
Cardiovascular Events ◽  
Cardiovascular Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Risk Reduction ◽  
Cardiovascular Outcome Trials ◽  
Lower Weight ◽  
Meta Regression

Abstract Background Glucose lowering drugs or strategies (GLDS) have varied effects on major adverse cardiovascular events (MACE) and heart failure (HF) in cardiovascular outcomes trials. Mechanisms driving cardiovascular risk reduction remain elusive. Methods We searched MEDLINE, PubMed, and meeting abstracts up to 11/21/2018 for large GLDS cardiovascular outcome trials (CVOTs) in patients with or at risk for type 2 diabetes. Primary endpoints of MACE and HF were evaluated with random effects risk ratios (RR) and explored by baseline CVD subgroups and meta-regression by weight change across treatment arms. Results In 27 GLDS CVOTs, a total 207,820 patients, median age 63 years, 64% male, 64% CVD and 11% with prior HF were studied over a mean 3.8 years with 20,118 (10%) patients having MACE and 7,212 (4%) a HF event. Compared with standard care, GLDS overall lowered MACE (RR 0.92, P<0.ehz745.01171) but not HF (RR 1.01, P=0.91). Across GLDS, the magnitude and directionality varied modestly for MACE RR (P-int=0.07) but markedly for HF (P-int<0.ehz745.01171). Meta-regression showed a change in HF RR by 6% (95% CI 3%-9%) per 1 kg weight gain/loss between treatment arms (P=0.0006; Figure). In 9 trials of GLDS that achieved marked weight loss (lifestyle, GLP1 agonists, SGLT2 inhibitors), MACE benefit was confined to patients with baseline CVD (RR 0.89 [0.84–0.95] versus without (RR 1.02 [0.91–1.15]; P-int=0.01) with consistent HF effect (RR 0.80 [0.72–0.88] vs RR 0.76 [0.56–1.03]; P-int=0.74). Heart Failure Risk and Changes in Weight Conclusion HF outcomes were improved with GLDS that lower weight. Among diabetes GLDS that lower weight, there was a robust risk reduction in atherothrombotic and heart failure events, with the MACE benefit confined to patients with established CVD. Acknowledgement/Funding Heart and Stroke Foundation

scholarly journals Does type 2 diabetes confer higher relative rates of cardiovascular events in women compared with men?

2019 ◽  
Vol 41 (13) ◽  
pp. 1346-1353 ◽  
Author(s):  
Morten Malmborg ◽  
Michelle D S Schmiegelow ◽  
Caroline H Nørgaard ◽  
Anders Munch ◽  
Thomas Gerds ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Cardiovascular Complications ◽  
Incidence Rates ◽  
Major Adverse Cardiovascular Events ◽  
Men And Women ◽  
Individual Level ◽  
Diabetes Status ◽  
Rate Ratios

Abstract Aims To investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age. Methods and results All Danish residents aged 40–89 years without a history major adverse cardiovascular events, including heart failure, as of 1 January 2012 until 31 December 2016 were categorized by diabetes-status and characterized by individual-level linkage of Danish nationwide administrative registers. We used Poisson regression to calculate overall and age-dependent incidence rates, incidence rate ratios, and women-to-men ratios for myocardial infarction, heart failure, ischaemic stroke, or cardiovascular death (MACE-HF). Among 218 549 (46% women) individuals with diabetes, the absolute rate of MACE-HF was higher in men than in women (24.9 vs. 19.9 per 1000 person-years). Corresponding absolute rates in men and women without diabetes were 10.1 vs. 7.0 per 1000 person-years. Comparing individuals with and without diabetes, women had higher relative rates of MACE-HF than men [2.8 (confidence interval, CI 2.9–2.9) in women vs. 2.5 (CI 2.4–2.5) in men] with a women-to-men ratio of 1.15 (CI 1.11–1.19, P &lt; 0.001). The relative rates of MACE-HF were highest in the youngest and decreased with advancing age for both men and women, but the relative rates were higher in women across all ages, with the highest women-to-men ratio between age 50 and 60 years. Conclusion Although men have higher absolute rates of cardiovascular complications, the relative rates of cardiovascular complications associated with diabetes are higher in women than in men across all ages in the modern era.

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