Empagliflozin improves clinical outcomes in T2D patients with CVD, CKD
Empagliflozin appears to be beneficial to type 2 diabetes (T2D) patients with established cardiovascular disease (CVD) and chronic kidney disease (CKD), yielding reductions in CV and all-cause mortality, as well as in heart failure and all-cause hospitalization compared with placebo, according to a study.
The findings are good news to the vulnerable population of patients with T2D, CKD and established CVD, with those having kidney disease being at increased risk of CV morbidity and mortality despite current standard of care, according to the authors.
In the study, the authors analysed data from 2,250 patients with T2D, established CVD and prevalent kidney disease at baseline who were enrolled in the EMPA-REG OUTCOME trial. These patients had been randomized to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo once daily in addition to standard of care. Overall, 67 percent had T2D for >10 years, 58 percent were receiving insulin, and 84 percent were treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
Compared with placebo, empagliflozin produced reductions in the following outcomes of interest: CV death (hazard ratio [HR], 0.71; 95 percent CI, 0.52–0.98), all-cause mortality (HR, 0.76; 0.59–0.99), hospitalization for heart failure (HR, 0.61; 0.42–0.87) and all-cause hospitalization (HR, 0.81; 0.72–0.92). [Circulation 2018;137:119-129]
The effect of empagliflozin on the said outcomes was consistent across the two doses studied, as well as across subgroups of patients by baseline renal function (estimated glomerular filtration rate [eGFR] <45, 45–<60, 60–<90, ≥90 mL·min−1·1.73 m−2) or albuminuria status (urine albumin-creatinine ratio >300, 30–≤300, <30 mg/g).
In terms of safety, empagliflozin had an adverse event (AE) profile that was similar across subgroups by renal function at baseline. AEs of particular concern in the present population, including urinary tract infection, acute renal failure, hyperkalaemia, fractures, lower limb amputations and hypoglycaemia, occurred at lower or similar rates with the drug vs placebo.
“Another clinically relevant finding was that, despite diminishing glucose-lowering efficacy with declining renal function, other clinical parameters, including blood pressure, were improved with empagliflozin regardless of renal status at baseline,” the authors noted.
“Hence, these hypothesis-generating data suggest that empagliflozin could address a significant unmet need in patients with chronic kidney disease,” they said, adding that “further outcome research is underway to assess whether empagliflozin could represent a treatment option to mitigate the risk of premature death and to reduce CV and healthcare burden in patients with CKD.”
In a linked commentary, Dr Jorge Plutzky from the Brigham and Women’s Hospital and Dr George Bakris from the University of Chicago Medicine noted that the present data open new clinical opportunities and compel more immediate, pressing clinical application of what clinicians now know. [Circulation 2018;137:130-133]
“Aggressive CV risk reduction may be easier for the physician to pursue when the clinical situation is obvious: Q waves on an ECG, a history of coronary stenting, or a chest scar from coronary bypass,” they wrote. “More challenging is recognizing the CV risk lurking when CKD and diabetes mellitus are present together, even without these more glaring CVD signals.”
While the positive findings from the EMPA-REG OUTCOME trial highlight the value of considering sodium/glucose cotransporter 2 (SGLT2) inhibitors as an intervention to improve CV outcomes in high-risk patients with diabetes and CKD, they raise the question of whether SGLT2 inhibitors may benefit other patients groups, whether the agents’ beneficial effects may be retained in the presence of significant CKD, and whether they can protect the kidney from further decline in settings of high CVD risk, Plutzky and Bakris said.