The sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin significantly reduced HbA1c, systolic and diastolic blood pressure levels in patients with type 2 diabetes and hypertension compared with placebo, according to the results of a study published recently in Diabetes Care.
The FDA recently approved empagliflozin as an addition to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2DM). Although clinical trials have shown that the drug is associated with decreases in systolic blood pressure, it is not approved as an antihypertensive agent.
Researchers led by Ilkka Tikkanen, MD, of the department of medicine at Helsinki University Central Hospital and Minerva Institute for Medical Research, Finland, conducted the EMPA-REG BP trial to assess the effects of 12 weeks of 10-mg and 25-mg empagliflozin on blood pressure and glycemic control in patients with T2DM and hypertension.
Researchers defined hypertension as a mean seated office systolic pressure of 130 to 159 mm Hg and diastolic pressure of 80 to 99 mm Hg. All patients were aged 18 years or older, had a body mass index of 45 kg/m2 or less, and had uncontrolled T2DM with an HbA1c of 7% to 10%. In addition, patients had to be on as many as two antihypertensive medications at the time of screening and during a 2-week, placebo run-in period.
The study included 825 patients who were randomly assigned to receive either 10-mg empagliflozin, 25-mg empagliflozin, or placebo once daily for 12 weeks.
At 12 weeks, patients in both the 10- and 25-mg empagliflozin groups had significant reductions in 24-hour ambulatory blood pressure monitoring (ABPM) levels compared with placebo. According to the researchers, they used ABPM to avoid any “white coat” effect seen with taking blood pressure measurements while in a physician’s office.
Patients assigned the empagliflozin 10-mg dose had an adjusted mean difference in 24-hour systolic blood pressure versus placebo of –3.44 mm Hg, and patients assigned the 25-mg dose, a difference of –4.16 mm Hg (P<.001 for both). Similarly, the adjusted mean difference versus placebo at 12 weeks for diastolic pressure was a decrease of 1.36 mm Hg for 10-mg empagliflozin and a decrease of 1.72 mm Hg for 25-mg empagliflozin (P<.001 for both).
Those patients with an ABPM level greater than 130/80 mm Hg at baseline had greater reduction in blood pressure compared with patients with a baseline ABPM of less than 130/80 mm Hg.
As seen in previous trials that have looked at glycemic control associated with empagliflozin, patients assigned the study drug also had significant reductions in HbA1c at 12 weeks. Compared with placebo, patients assigned the 10-mg dose had a mean 0.62% reduction in HbA1c, and those assigned the 25-mg dose had a mean 0.65% reduction (P<.001 for both).
In their discussion of the results, the researchers noted that it is not yet fully known the mechanism by which empagliflozin reduces blood pressure.
As part of its approval, the FDA required that cardiovascular outcomes associated with empagliflozin be examined further. The ongoing EMPA-REG OUTCOME trial is expected to provide physicians with more information about the safety of empagliflozin on cardiovascular and microvascular outcomes in patients with T2DM who are at high cardiovascular risk.
Tikkanen I, Narko K, Zeller C, et al on behalf of the EMPA-REG BP Investigators. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2014;doi:10.2337/dc14-1096.