We update the clinical findings of Glucagon-like peptide-1 receptor agonists, DPP-4 inhibitors and Sodium/glucose cotransporter 2 inhibitors in glycemic control and the risk or progression of cardiovascular disease in diabetic patients.
<b>Context:</b> Increased vascular cell adhesion molecule-1 (VCAM-1) has been reported to be a critical link between obesity and atherosclerotic cardiovascular diseases while dipeptidyl peptidase-4 (DPP-4) has been implicated in the development of disrupted glucose regulation and inflammation.
In the cardiovascular outcome trials (CVOT) EMPA-REG OUTCOME, TECOS and SAVOR-TIMI 53, empagliflozin [sodium/glucose cotransporter 2 (SGLT2) inhibitor], sitagliptin and saxagliptin [both dipeptidyl peptidase 4 (DPP4) inhibitors] + standard of care (SoC) were compared to SoC in patients with type 2 diabetes and established cardiovascular disease (CVD).
In fully adjusted models, use of SGLT2 inhibitors was associated with a decreased risk of developing CVD compared with use of sulfonylureas (HR, 0.50; 95% CI, 0.45, 0.55) and DPP-4 inhibitors (HR, 0.57; 95% CI, 0.52, 0.62), respectively.
Conversely, dipeptidyl peptidase 4 (DPP-4) inhibitors did not significantly affect atherosclerotic CVD end-points and some actually increased the risk of HF hospitalizations.
The large trials evaluating the dipeptidyl peptidase-4 inhibitors sitagliptin, alogliptin and saxagliptin demonstrated safety for cardiovascular disease.
There is lack of solid information on differences in the therapeutic effects of SGLT2 inhibitors and DPP4 inhibitors on multiple risk factors for cardiovascular diseases.
We herein review the available clinical studies in cardiovascular effects played by each DPP-4 inhibitor and discuss the prospective application of DPP-4 inhibitors on cardiovascular diseases.
Dipeptidyl peptidase IV (DPP-4) is well known for its role in glucose homeostasis, and DPP-4 inhibitor (DPP-4i) exhibits multiple actions in cardiovascular diseases.
Thus, we aimed to evaluate whether the heart failure protective effect of SGLT-2i differs depending on the underlying CVD and the prescription period compared with dipeptidyl peptidase-4 inhibitors (DPP-4i).
Among them, the sodium-glucose co-transporter-2 (SGLT-2) inhibitors (gliflozins) and selected agents from the incretin mimetics or enhancers, such as the glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins), appear to confer cardiovascular safety and/or protection in patients with underlying, or at high risk for, cardiovascular disease.
Recently, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin, a major anti-hyperglycaemic agent, has received substantial attention as a therapeutic target for cardiovascular diseases via enhancing the number of circulating endothelial progenitor cells (EPCs).
To examine whether dipeptidyl peptidase 4 inhibitors (DPP-4I) increase acute pancreatitis risk in older patients and whether the association varies by age, sex, and history of cardiovascular disease (CVD).
Combination therapy of metformin plus dipeptidyl peptidase-4 inhibitor versus metformin plus sulfonylurea and their association with a decreased risk of cardiovascular disease in type 2 diabetes mellitus patients.
These results indicate that the DPP4/GLP-1-adiponectin axis is a novel therapeutic target for the treatment of vascular aging and cardiovascular disease under chronic stress conditions.
A decreased risk of hospitalization for CVDs was found among patients with a history of visit for CVDs (aHR, 0.73; 95% CI, 0.56-0.97) or with >2.5 years' duration of type 2 diabetes (aHR, 0.77; 95% CI, 0.66-0.91) in the DPP-4 inhibitors versus glimepiride group.DPP-4 inhibitors did not increase cardiovascular risk compared with glimepiride regardless of CVD history and diabetes duration.
We evaluated the incidence of acute pancreatitis and pancreatic cancer in patients with type 2 diabetes and cardiovascular disease who were treated with sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i).
Cardiovascular effects of dipeptidyl peptidase-4 inhibitor in diabetic patients with and without established cardiovascular disease: a meta-analysis and systematic review.