The possible mechanisms are “multidimensional,” according to investigators, and might involve changes in arterial stiffness, cardiac function, and cardiac oxygen demand, as well as cardiorenal effects and reductions in albuminuria and uric acid. The drug is also believed to have modest effects on weight, blood pressure, and belly fat, along with lowering blood sugar.
For the double-blind trial, Bernard Zinman, MD, of Mount Sinai Hospital in Toronto, and colleagues randomly assigned 7,020 type 2 diabetes patients with cardiovascular disease (CVD) to receive empagliflozin (10 or 25 mg) or placebo once daily. The drug, an inhibitor of sodium-glucose cotransporter 2, reduces renal reabsorption of glucose and may be given alone or as add-on therapy.
After a median 2.6 years of treatment, 10.5% of patients in the empagliflozin groups experienced the composite outcome of cardiovascular death, heart attack, or stroke compared with 12.1% in the placebo group, according to results published in the New England Journal of Medicine. These results were driven by a 38% reduction in the relative risk of cardiovascular death (3.7% vs. 5.9% for placebo). Patients also had lower risks of hospitalization for heart failure and premature death from any cause. The dose of empagliflozin mattered little.
Patients receiving empagliflozin had an increased rate of genital infection, but experienced no increase in other adverse events compared with placebo (e.g., diabetic ketoacidosis, volume depletion, etc.).
“These benefits were observed in a population with established cardiovascular disease in whom cardiovascular risk factors, including blood pressure and dyslipidemia, were well treated with the use of renin-angiotensin-aldosterone system inhibitors, statins, and acetylsalicylic acid,” the researchers noted. Empagliflozin may increase both low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol. Many patients did not reach glucose targets.
The study was funded by Boehringer Ingelheim and Eli Lilly, the manufacturers of empagliflozin (Jardiance). The medication may decrease estimated glomerular filtration rate (eGFR), so patients needed to have an eGFR of at least 30 mL/min/1.73m2 to participate. Renal function was maintained during the study. The safety and efficacy of empagliflozin has not been established in patients with severe renal impairment or end-stage renal disease, or those receiving dialysis.
- Zinman, B; Wanner, C; Lachin, JM; et al. NEJM; doi: 10.1056/NEJMoa1504720.