Cardiovascular outcome studies with incretin-based therapies: Comparison between DPP-4 inhibitors and GLP-1 receptor agonists.

Scheen, André

doi:10.1016/j.diabres.2017.03.009

Article (Scientific journals)

Cardiovascular outcome studies with incretin-based therapies: Comparison between DPP-4 inhibitors and GLP-1 receptor agonists.

Scheen, André

2017 • In Diabetes Research and Clinical Practice, 127, p. 224-237

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https://hdl.handle.net/2268/210421

DOI
10.1016/j.diabres.2017.03.009

PubMed
28402902

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Keywords :

Cardiovascular disease; Clinical trial; DPP-4 inhibitors; GLP-1 receptor agonists; Mortality; Type 2 diabetes

Abstract :

[en] Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced. However, LEADER showed a significant reduction in major cardiovascular events, myocardial infarction, cardiovascular and all-cause mortality in patients treated by liraglutide compared to placebo. These positive results contrasted with the non-inferiority results with lixisenatide in ELIXA. They were partially confirmed with semaglutide in SUSTAIN 6 despite the absence of reduction in cardiovascular mortality. Hospitalisation for heart failure was not increased except with saxagliptin in SAVOR-TIMI 53. The reasons for different outcomes between trials remain largely unknown as well as the precise underlying mechanisms explaining the cardiovascular protection by liraglutide. The clinical relevance of results with DPP-4is and GLP-1RAs is discussed. Ongoing trials with linagliptin and several once-weekly GLP-1RAs should provide new insights into remaining fundamental questions.

Disciplines :

Cardiovascular & respiratory systems
Pharmacy, pharmacology & toxicology
Endocrinology, metabolism & nutrition

Author, co-author :

Scheen, André ; Université de Liège > Département des sciences cliniques > Département des sciences cliniques

Language :

English

Title :

Cardiovascular outcome studies with incretin-based therapies: Comparison between DPP-4 inhibitors and GLP-1 receptor agonists.

Publication date :

2017

Journal title :

Diabetes Research and Clinical Practice

ISSN :

0168-8227

eISSN :

1872-8227

Publisher :

Elsevier, Amsterdam, Netherlands

Volume :

127

Pages :

224-237

Peer reviewed :

Peer Reviewed verified by ORBi

Commentary :

Available on ORBi :

since 11 May 2017

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