AstraZeneca presented new data at the American Diabetes Association’s (ADA) 77th Scientific Sessions underpinning the safety profile of Farxiga (dapagliflozin) with an analysis of data pooled from dapagliflozin clinical trials, as well as three new cardiovascular (CV) outcomes analyses from the ongoing CVD-REAL study, the first large real-world evidence study of its kind evaluating treatment with SGLT-2 inhibitors (SGLT-2i), including dapagliflozin.

In an updated safety analysis, data pooled from 30 Phase IIb/III clinical trials for dapagliflozin showed no new safety signals and the incidence of adverse events was generally similar to that in the control groups. Importantly, there was no imbalance in lower-limb amputations, with eight (0.1%) patients and seven (0.2%) patients identified in the dapagliflozin and control groups, respectively.

Following the primary publication of the CVD-REAL study in May 2017, three new analyses presented at ADA add to the ongoing evaluation of earlier treatment with SGLT-2is and in broader patient populations with type-2 diabetes (T2D). The analyses evaluated effects in additional real-world patient populations, including CV endpoints specific to dapagliflozin:

A two-country analysis of more than 30,000 patients with T2D showed a significant reduction in the rates of hospitalisation for kidney disease by 62% (p<0.001), hospitalisation for heart failure (HF) by 37% (p<0.001) and death from any cause by 27% (p=0.003) for patients using dapagliflozin versus DPP-4 inhibitors (DPP-4is).

A three-country analysis of nearly 100,000 patients with T2D showed a significant reduction in rates of CV death by 47% (p<0.001) and hospitalisation for HF by 30% (p<0.001), for patients new to SGLT-2is versus other T2D medicines.

A late-breaking oral presentation analysing data from more than 300,000 patients across five countries will explore the rates of HF and death in patients with T2D, both with and without CV disease, receiving treatment with SGLT-2is versus other T2D medicines (Oral 377-OR, Tuesday June 13, 10:45am PDT).

Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, said: “SGLT-2 inhibitors are being prescribed with greater frequency for patients with type-2 diabetes, so it is vital that we have a clear understanding of the safety profile of these medicines and examine their effectiveness in a real-world setting. The data we are presenting at ADA underpins the safety of Farxiga and highlights the potential for earlier use of the SGLT-2 inhibitor class, and in broader patient populations than originally understood.”

The CVD-REAL study is ongoing and future analyses will be conducted using this dataset as well as data from additional countries. The data for the study were obtained from anonymised real-world sources including medical records, claims databases and national registries, and were not independently adjudicated or verified against source documents. The analysis was validated by the independent academic statistical group at St. Luke’s Mid America Heart Institute, Kansas City, USA. While CVD-REAL was a large study with a robust propensity-matching technique, given its observational nature the possibility of residual, unmeasured confounding factors cannot be definitively excluded.

Dapagliflozin is indicated as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Dapagliflozin is not indicated to reduce the risk of CV events, death or hospitalisation for heart failure. The dapagliflozin cardiovascular outcomes trial, DECLARE, is ongoing and expected to provide data in 2019 at the latest.