Observational data hint at additional dapagliflozin benefits
medwireNews: A real-world study based on DECLARE-TIMI 58 inclusion and outcome criteria shows that dapagliflozin not only reduces cardiovascular (CV) risk among patients with type 2 diabetes, in line with the original trial results, but may also lower all-cause mortality risk.
The DECLARE-like population included 7102 Swedish patients initiating treatment with the sodium-glucose cotransporter (SGLT)2 inhibitor dapagliflozin between 2013 and 2016 and 21,306 initiating other glucose-lowering drugs (GLDs) with the exception of SGLT2 inhibitors. The two groups were matched by propensity scoring.
All of the patients met the main DECLARE-TIMI 58 inclusion criteria, being age 40 years and older (mean age 66 years) with established CV disease (35%) or aged 55 years and older for men and 60 years and older for women with CV risk factors (hypertension or dyslipidemia).
As reported in Diabetes, Obesity and Metabolism, DECLARE-like patients receiving dapagliflozin had a significant 21% lower risk for hospitalization for heart failure or CV mortality than those receiving other GLDs, with incidence rates of 20.6 versus 26.0 events per 1000 patient–years, respectively.
By contrast, there was no significant reduction in rates of major adverse CV events, defined as CV mortality, myocardial infarction, or stroke, at 26.1 versus 28.9 events per 1000 person–years.
When analysed separately, the risks for HHF and CV mortality were a significant 21% and 25% lower, respectively, with dapagliflozin than with other GLDs, but there were no significant differences between the two groups in the risk for myocardial infarction or stroke.
Of note, and in contrast to DECLARE-TIMI 58, DECLARE-like patients who received dapagliflozin had a significant 37% lower risk for all-cause mortality than those who received other GLDs, with rates of 16.1 and 25.8 events per 1000 person–years, respectively.
Johan Bodegård (AstraZeneca Nordic-Baltic, Oslo, Norway) and co-researchers say that this discordance, as well as that for CV mortality, which was also not significantly reduced with dapagliflozin in DECLARE-TIMI 58 study, “may be explained by the large difference in population frailty observed between the two studies.”
They point out that all-cause mortality was 70% higher in the DECLARE-like population than in DECLARE-TIMI 58, suggesting that the observational cohort was “substantially more frail.”
“Hence, due to the lower population frailty in DECLARE-TIMI 58 it is likely that the beneficial effects of dapagliflozin on CV mortality risk is underestimated, both when compared with other [CV outcome trials] and with patient populations in a real-world setting,” the researchers remark.
They add that the effect of dapagliflozin could potentially be greater in the general type 2 diabetes population, which is even frailer, with all-cause mortality rates as high as 36 events per 1000 patient–years, compared with 25.6 events per 1000 patient–years in the DECLARE-like population.
Bodegård and co-authors say they have “shown that assessment of drug treatments in a real-world setting could add valuable insights if carried out correctly and that results could be an important complement to randomized controlled studies.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group