New data including real-world CV outcomes with SGLT2 inhibitor support its safety profileNews - June 13, 2017
New data underpinning the safety profile of the SGLT-2 inhibitor (SGLT-2i) dapagliflozin were presented at the American Diabetes Association’s 77th Scientific Sessions. Both an analysis of data pooled from dapagliflozin clinical trials, and three new cardiovascular (CV) outcomes analyses from the ongoing CVD-REAL study were shared. CVD-REAL is the first large real-world evidence study of its kind evaluating treatment with 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 hospitalization for kidney disease by 62% (P<0.001), hospitalization for heart failure (HHF) 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 HHF by 30% (p<0.001), for patients new to SGLT-2is versus other T2D medicines
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 anonymized 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 glycemic control in adults with T2D. Dapagliflozin is not indicated to reduce the risk of CV events, death or HHF. The dapagliflozin CV outcomes trial, DECLARE, is ongoing and expected to provide data in 2019 at the latest.