2015
DOI: 10.4093/dmj.2015.39.5.373
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Dipeptidyl Peptidase 4 Inhibitors and the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: A Tale of Three Studies

Abstract: Dipeptidyl peptidase 4 (DPP4) inhibitors have been touted as promising antihyperglycemic agents due to their beneficial effects on glycemia without inducing hypoglycemia or body weight gain and their good tolerability. Beyond their glucose-lowering effects, numerous clinical trials and experimental studies have suggested that DPP4 inhibitors may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms or involving other substrates. Since 2008, regulatory… Show more

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Cited by 35 publications
(24 citation statements)
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“…However, three large randomized clinical trials failed to show that DPP4 inhibitors can decrease cardiovascular events, and one of them indicated an unexpected increase in the risk of heart failure in T2DM patients15. Moreover, a meta-analysis showed that DPP4 inhibitors do not decrease the risk of all-cause and cardiovascular mortality16.…”
Section: Discussionmentioning
confidence: 99%
“…However, three large randomized clinical trials failed to show that DPP4 inhibitors can decrease cardiovascular events, and one of them indicated an unexpected increase in the risk of heart failure in T2DM patients15. Moreover, a meta-analysis showed that DPP4 inhibitors do not decrease the risk of all-cause and cardiovascular mortality16.…”
Section: Discussionmentioning
confidence: 99%
“…These findings led to the requirement by regulatory agencies for cardiovascular safety studies for all new antihyperglycemic agents. The dipeptidyl-peptidase 4 inhibitors (DPP-4i), saxagliptin and alogliptin but not sitagliptin, have also been associated with increased risk for hospitalization of HF by the Food and Drug Administration (FDA) and European Medicines Agency (EMA); responsible mechanisms are, however, not currently known 13, 14 .…”
Section: Anti-hyperglycemic Agents and Cardiovascular Safety Trialsmentioning
confidence: 99%
“…This could potentially explain the difference in the rates of heart failure exacerbations seen with saxagliptin but not alogliptin. [36] Although a few meta-analyses have also shown an increase in the rates of heart failure exacerbation with the use of DPP4 inhibitors, these results may be skewed by the sample size of the SAVOR-TIMI trial that were taken into consideration when analyzing the results because the SAVOR-TIMI population represented the largest cohort in these meta-analyses. [50] However, if truly saxagliptin is associated with heart failure exacerbations, a few authors have postulated that this could be secondary to elevated end-diastolic volumes and worsening endothelial dysfunction caused by the DPP4 inhibitors.…”
Section: Discussionmentioning
confidence: 99%
“…[2] Within these tissues, the enzyme acts on multiple substrates of which the most widely studied ones are GLP-1and glucose-dependent insulinotropic polypeptide (GIP). [36] GLP-1 and GIP proteins act by means of a feedback loop that is based on levels of serum glucose. Hyperglycemia serves as a stimulus for GLP-1 secretion which then acts upon the pancreatic β-cells to release insulin and also simultaneously inhibit hepatic glucagon secretion.…”
Section: Dpp4 Inhibitorsmentioning
confidence: 99%