Treatment with empagliflozin, an investigational sodium-glucose cotransporter 2 (SGLT2) inhibitor, was associated with benefits for blood pressure as well as glycemic control in a 3-month study of more than 800 patients with type 2 diabetes and hypertension.
The study results were released May 15 at the annual meeting of the American Association of Clinical Endocrinologists, held in Las Vegas, by Dr. Afshin Salsali, an endocrinologist and executive director, diabetes and metabolism, at Boehringer Ingelheim Pharmaceuticals, the manufacturer of the drug.
Since hypertension is common among patients with type 2 diabetes and is associated with diabetes-related complications, a treatment approach that includes control of blood pressure and hyperglycemia might reduce the risk of cardiovascular complications and mortality in these patients, Dr. Salsali said in an interview before the meeting.
In the phase III randomized, controlled study, 823 patients were treated with either 10 mg of empagliflozin (276 patients), 25 mg of empagliflozin (276), or placebo (271), once a day for 12 weeks. At baseline, the patients’ mean seated systolic and diastolic blood pressures were 130-159 mm Hg and 80-99 mm Hg, respectively; their mean age was 60 years; and their mean body mass index was about 33 kg/m2, in the obese category.
The two primary endpoints were changes from baseline in hemoglobin A1c and mean 24-hour systolic blood pressure as measured by ambulatory blood pressure monitoring, at week 12.
At 12 weeks, the mean reductions in HbA1c from baseline over placebo were 0.62% for those on the 10-mg dose and 0.65% among those on the 25-mg dose, both significant differences. The reductions in mean 24-hour systolic blood pressure were also significant, compared with placebo: They were 3.44 mm Hg with the 10-mg dose and 4.16 mm Hg with the 25-mg dose, according to Dr. Salsali.
In addition, the mean reductions from baseline in 24-hour diastolic blood pressure were significant at week 12, compared with placebo, a secondary endpoint. Those reductions were 1.36 mm Hg for patients on the 10-mg dose and 1.72 mm Hg for those on the 25-mg dose.
About half of the patients in each group reported adverse events. "Events consistent with volume depletion" were reported in one patient on the 10-mg dose of empagliflozin and one in the placebo group.
This study is unique because it utilized the gold standard for monitoring blood pressure to evaluate the effects of the drug on blood pressure, Dr. Salsali said.
Currently, empagliflozin is approved only in Australia, and it is under review in the United States and Europe. In March, Boehringer Ingelheim and Eli Lilly announced that the Food and Drug Administration had issued a complete response letter stating that deficiencies at a site where empagliflozin would be manufactured needed to be resolved before approval. But the FDA has not requested that any new clinical trials be completed for approval, according to the statement issued by Boehringer Ingelheim.
In March, the drug was recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency for treating adults with type 2 diabetes.
In January, the FDA approved the SGLT2 inhibitor dapagliflozin for the treatment of type 2 diabetes. The first drug in this class to be approved in the United States was canagliflozin (Invokana), approved in March 2013. These agents, taken orally, work by inhibiting SGLT2 that is expressed in the kidney, reducing renal glucose reabsorption, increasing urinary excretion of glucose, and reducing plasma glucose levels.
The study was sponsored by Boehringer Ingelheim; Eli Lilly was a collaborator. Dr. Salsali is an employee of Boehringer Ingelheim USA. Other authors of the study included employees of Boehringer Ingelheim, including Boehringer Ingelheim Finland.