Abstract 9520: Dapagliflozin, a Novel Antihyperglycemic Agent that Promotes Urinary Glucose Excretion, Reduces Systolic Blood Pressure in Patients with Type 2 Diabetes Mellitus

Background: Obesity and hypertension commonly occur in patients with type 2 diabetes mellitus (T2DM). Dapagliflozin (DAPA), a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia in T2DM by increasing urinary glucose excretion leading to osmotic diuresis, caloric loss, and weight loss. Using prospective exploratory analyses from 3 Phase III studies in patients with T2DM, we evaluated whether DAPA also reduces blood pressure (BP). Methods: Seated systolic and diastolic BP, heart rate, proportion of patients with measured orthostatic hypotension, and adverse events of hypotension, dehydration or hypovolemia were assessed in each study. Study 1 ( NCT00660907 ): randomized to DAPA or glipizide added to open-label metformin; both treatments were up-titrated, based on tolerability and glycemic response, to a maximum of 10 mg/day or 20 mg/day, respectively. Study 2 ( NCT00680745 ): randomized to DAPA 2.5, 5, or 10 mg or placebo added to open-label glimepiride. Study 3 ( NCT00673231 ): randomized to DAPA 2.5, 5, or 10 mg or placebo added to open-label insulin ± oral antidiabetic agents. Use of anti-hypertensive medication was not controlled in these studies. Results: DAPA reduced mean systolic BP, and to a lesser extent diastolic BP (Table), without increasing mean heart rate or proportions of patients experiencing orthostatic hypotension. Adverse events of hypotension, dehydration or hypovolemia were reported in 1.5%, 0.4%, and 1.6% of patients receiving DAPA vs 0.7%, 0%, and 1% receiving glipizide or placebo in studies 1, 2 and 3, respectively. These episodes were of mild or moderate intensity and none led to study discontinuation or hospitalization. Conclusions: DAPA modestly reduces systolic BP in patients with T2DM who were mostly receiving treatment for hypertension. Further studies employing controlled antihypertensive therapy are required to validate the BP-lowering effect of dapagliflozin in T2DM patients with hypertension.