Dapagliflozin and cardiovascular outcomes: anything else to DECLARE?

ABSTRACT

Introduction: Individuals with type 2 diabetes mellitus (T2DM) have increased cardiovascular risk with regulatory agencies requiring cardiovascular outcome trials (CVOTs) for the approval of new antidiabetic drugs.

Areas covered: In this paper, the authors critically discuss the background, trial design, results and implications of a recent CVOT [NCT01730534; DECLARE-TIMI 58 study], which demonstrated that dapagliflozin was non-inferior to placebo in terms of major adverse cardiovascular events, and superior for the occurrence of hospitalization for heart failure (HF) and composite renal endpoints, thus confirming the cardiovascular benefit of sodium-glucose co-transporter-2 (SGLT2) inhibitors. No statistically-significant effects were found for amputations, fractures, and stroke (debated safety issues having emerged in previous CVOTs).

Expert opinion: DECLARE-TIMI 58 is the longest (4.2 years of follow up), largest (>17,000 participants) and most inclusive (only 41% of individuals with established atherosclerotic cardiovascular disease) CVOT raising the debate towards SGLT2 inhibitor therapy in primary prevention and the potential use of these drugs also in patients with HF without T2DM and other subpopulations.

KEYWORDS:

• Dapagliflozin
• sodium-glucose co-transporter-2 inhibitor
• cardiovascular outcome trial
• major adverse cardiovascular events
• heart failure
• type 2 diabetes

Declaration of interest

G Marchesini has been involved in clinical studies funded by Sanofi, Eli Lilly and Company, Novo Nordisk, Janssen Pharmaceuticals, GlaxoSmithKline, Genfit SA and Gilead Sciences. He also has served on advisory boards for Gilead Sciences, Eli Lilly and AstraZeneca. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee is an employee of AstraZeneca. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This manuscript was not funded. Authors are supported by Institutional funds from the University of Bologna.