Elsevier

The Lancet

Volume 385, Issue 9982, 23–29 May 2015, Pages 2022-2024
The Lancet

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DPP-4 inhibitors and risk of heart failure EXAMINEd

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  • Treatment paradigm shifting implications of recent cardiovascular outcome trials: Core insights on the brink of the 2020ies

    2020, Diabetes Research and Clinical Practice
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    Also a meta-analysis of the effects of DPP-4is on the single components of MACE did not show any beneficial signals with regard to MI, stroke, CV death, or the composite of MI and stroke [42]. Unexpectedly, heterogeneity was found regarding a till to date unexplained differential risk of hHF [1–4,43–47], with sitagliptin and linagliptin clearly not being associated with an increased rate of hHF [46–48]. As a clinical implication of these results, the latter two drugs have been named preferred treatment options in patients at increased risk for HF in current guidelines [22,23,48,49].

  • Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes

    2017, American Journal of Cardiology
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    By contrast in the EXAMINE trial, which randomized 5380 T2DM patients with an acute coronary syndrome to receive alogliptin or placebo, the incidence of HF was comparable among the treatment arms (3.1% and 2.9%, respectively).54 However, post hoc analyses showed that alogliptin increased HF incidence in patients who had signs of HF at the time of randomization (HR 1.76; 95% CI, 1.07-2.90).57 Hence, data from SAVOR-TIMI 53 and EXAMINE confirmed that DPP-4 inhibitors may increase HF hospitalization in patients with pre-existing HF and high brain natriuretic peptide (BNP) levels at baseline (Table 3).

  • Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes

    2017, American Journal of Medicine
    Citation Excerpt :

    By contrast in the EXAMINE trial, which randomized 5380 T2DM patients with an acute coronary syndrome to receive alogliptin or placebo, the incidence of HF was comparable among the treatment arms (3.1% and 2.9%, respectively).54 However, post hoc analyses showed that alogliptin increased HF incidence in patients who had signs of HF at the time of randomization (HR 1.76; 95% CI, 1.07-2.90).57 Hence, data from SAVOR-TIMI 53 and EXAMINE confirmed that DPP-4 inhibitors may increase HF hospitalization in patients with pre-existing HF and high brain natriuretic peptide (BNP) levels at baseline (Table 3).

  • Cardiovascular outcome trials for anti-diabetes medication: A holy grail of drug development?

    2016, Indian Heart Journal
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    Further, for certain findings of a trial, a potential mechanistic explanation may not be available and it may even conflict the current knowledge on the subject. E.g. the increased risk of heart failure in the Saxagliptin arm of SAVOR-TIMI despite a positive effect of GLP-1 on heart failure in animal models.43 Rapid reduction of CV mortality starting within the first year in subjects using empagliflozin in the EMPAREG OUTCOME trial, which conflicts with the known potential glycemic benefits and the known potential CV risk benefits of the drug.13

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