Empagliflozin, an investigational drug to treat type 2 diabetes that is being developed by Boehringer Ingelheim Pharma, lowered blood pressure (BP) in hypertensive type 2 diabetics and reduced blood glucose levels during 12 weeks of treatment. Afshin Salsali, MD, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA, presented findings of the 12 Week Efficacy and Safety Study of Empagliflozin (BI 10773) in Hypertensive Patients With Type 2 Diabetes Mellitus [EMPA-REG BP; NCT01370005], a placebo-controlled Phase 3 trial (randomized, double-blind).

Prior 24-week Phase 3 clinical trials (randomized, double-blind) established the efficacy of empagliflozin (10 and 25 mg) in reducing systolic BP compared with placebo among patients with type 2 diabetes [Häring H-U et al. Diabetes Care 2014; Kovacs CS et al. Diabetes Obes Metab 2014; Häring H-U et al. Diabetes Care 2013; Roden M et al. Lancet Diabetes Endocrinol 2013]. The effect on blood sugar remained unclear.

The present study involved 823 subjects with type 2 diabetes and high BP (130/80 to 159/99 mm Hg) who were randomly assigned to receive placebo (n = 271), empagliflozin−10 mg (n = 276), and empagliflozin−25 mg (n = 276). The baseline demographics and clinical characteristics of the randomized patients were similar (Table 1).

At baseline, the majority (63%) had an estimated glomerular filtration rate of 60 to 90 mL/min/1.73 m². All patients wore an ambulatory BP cuff that monitored systolic and diastolic BP every hour for 24 hours at baseline (before treatment) and after 12 weeks of treatment. Blood samples were also acquired at baseline and 12 weeks to determine HbA_1c levels as a measure of long-term blood sugar control.

The 24-hour pattern of systolic BP was almost identical for the 3 subject groups at baseline. At Week 12, while the 24-hour systolic BP curves for the 3 groups were similar in shape, the placebo group consistently displayed higher BP than either empagliflozin group. Empagliflozin−25 mg produced slightly lower 24-hour systolic BP than empagliflozin−10 mg.

Similar results were found for diastolic BP. On average, systolic and diastolic BP among subjects who received the 25 mg of empagliflozin decreased by 4.2 mm Hg (p < .001) and 1.7 mm Hg (p < .01), respectively, compared with placebo. The average decrease in systolic and diastolic BP among patients who received the 10 mg of empagliflozin was 3.4 mm Hg (p < .001) and 1.4 mm Hg (p < .01), respectively, compared with placebo.

From baseline to Week 12, the average HbA_1c level dropped by 0.62% and 0.65% with 10 and 25 mg of empagliflozin, respectively, compared with placebo. Subjects tolerated empagliflozin well, with no increased rate of side effects compared with placebo. Most adverse events that occurred in all 3 groups were mild.

The authors speculate that the improved blood sugar levels evident in subjects receiving empagliflozin reflect reduced glucose reabsorption in the kidneys, which leads to glucose elimination in the urine. The findings suggest the potential of empagliflozin to reduce the risk of cardiovascular events with longer-term treatment. This possibility is being addressed in the long-term EMPA-REG OUTCOME trial [Zinman B et al. Cardiovasc Diabetol 2014], which is expected to finish in 2015. The primary end point of the latter trial is the time to first occurrence of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.