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Review
. 2016 Aug 11;15(1):111.
doi: 10.1186/s12933-016-0431-4.

Continued efforts to translate diabetes cardiovascular outcome trials into clinical practice

Angelo Avogaro  1 , Gian Paolo Fadini  2 , Giorgio Sesti  3 , Enzo Bonora  4 , Stefano Del Prato  5
Affiliations
Review

Continued efforts to translate diabetes cardiovascular outcome trials into clinical practice

Angelo Avogaro et al. Cardiovasc Diabetol. .

Abstract

Diabetic patients suffer from a high rate of cardiovascular events and such risk increases with HbA1c. However, lowering HbA1c does not appear to yield the same benefit on macrovascular endpoints, as observed for microvascular endpoints. As the number of glucose-lowering medications increases, clinicians have to consider several open questions in the management of type 2 diabetes, one of which is the cardiovascular risk profile of each regimen. Recent placebo-controlled cardiovascular outcome trials (CVOTs) have responded to some of these questions, but careful interpretation is needed. After general disappointment around CVOTs assessing safety of DPP-4 inhibitors (SAVOR, TECOS, EXAMINE) and the GLP-1 receptor agonist lixisenatide (ELIXA), the EMPA-REG Outcome trial and the LEADER trial have shown superiority of the SGLT2-I empagliflozin and the GLP-1RA liraglutide, respectively, on the 3-point MACE outcome (cardiovascular death, non-fatal myocardial infarction or stroke) and cardiovascular, as well as all-cause mortality. While available mechanistic studies largely support a cardioprotective effect of GLP-1, the ability of SGLT2 inhibitor(s) to prevent cardiovascular death was unexpected and deserves future investigation. We herein review the results of completed CVOTs of glucose-lowering medications and suggest a possible treatment algorithm based on cardiac and renal co-morbidities to translate CVOT findings into clinical practice.

Keywords: Cardiovascular disease; Cardiovascular outcome trials; Complications; Diabetes; Treatment.

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Figures

Fig. 1
Fig. 1
A treatment algorithm based on cardiac and renal co-morbidities and CVOTs. 1To be used with caution because of the risk of hypoglycemia; 2consider dose reduction (except for linagliptin) and monitor eGFR frequently; 3preferred in the presence of marked insulin resistance; 4initiation of therapy currently not recommended. aUKPDS; bPROACTIVE trial; cSAVOR; dTECOS, eEXAMINE; fLEADER trial; gEMPA-REG Outcome trial; hORIGIN trial; kADVANCE; jELIXA; mDIGAMI 1
Fig. 2
Fig. 2
The interplay between data derived from CVOTs and real world evidence for assessing the cardiovascular effects of glucose-lowering agents. RSG rosiglitazone, CVOTs cardiovascular outcome trials, RWE real world evidence, RR risk ratio
See this image and copyright information in PMC

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