J Lipid Atheroscler.  2018 Jun;7(1):32-41. 10.12997/jla.2018.7.1.32.

Cardiovascular Outcome Trials of Incretin Therapy (Dipeptidyl Peptidase-4 Inhibitors/Glucagon-Like Peptide-1 Receptor Agonist)

• Jeong IK

• KMID: 2416256
• DOI: http://doi.org/10.12997/jla.2018.7.1.32

Abstract

In 2008, the United States Food and Drug Administration issued guidance which mandated long-term cardiovascular outcome trials (CVOTs) to assess the safety of new antidiabetic drugs for type 2 diabetes. Since 2008, three CVOTs that have studied dipeptidyl peptidase-4 (DPP-4) inhibitors and four CVOTs of a glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) have been reported. Each of the completed CVOTs showed the noninferiority of respective drugs to placebo for primary CV composite endpoint. Among them, liraglutide and semaglutide showed a reduction of major adverse cardiovascular events. However, the mechanisms for the observed cardiovascular differences between DPP-4 inhibitors and GLP-1RA, and across individual GLP-1RA are not clearly understood. Therefore, this review will summarize the CVOTs of the DPP-4 inhibitors and GLP-1RA, interpretation of cardioprotective results of incretin-based therapy and the possible mechanism of action.

Keyword

Cardiovascular outcome trials; Diabetes mellitus, Type 2; Dipeptidyl-peptidase IV inhibitors; Glucagon-like peptide-1 receptor agonist

MeSH Terms

Diabetes Mellitus, Type 2
Dipeptidyl-Peptidase IV Inhibitors
Glucagon-Like Peptide 1
Hypoglycemic Agents
Incretins*
Liraglutide
United States Food and Drug Administration
Dipeptidyl-Peptidase IV Inhibitors
Glucagon-Like Peptide 1
Hypoglycemic Agents
Incretins
Liraglutide

Figure

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  Fig. 1 Completed and ongoing CVOTs of DPP-4 inhibitors and GLP-1RAs. Solid line means completed clinical trials. Dotted line means ongoing clinical trials. CVOT; cardiovascular outcome trial, DPP-4; dipeptidyl peptidase-4, GLP-1RA; glucagon-like peptide-1 receptor agonist, 3-P; 3-point, 4-P; 4-point, MACE; major adverse cardiovascular event.

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  Fig. 2 HR (95% CI) for the MACEs versus placebo/comparator treatment from CVOTs using DPP-4 inhibitors and GLP-1RA. HR; hazard ratio, CI; confidence interval, MACE; major adverse cardiovascular event, CV; cardiovascular, CVOT; cardiovascular outcome trial, DPP-4; dipeptidyl peptidase-4, GLP-1RA; glucagon-like peptide-1 receptor agonist.

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