Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin-angiotensin system blockade

Blood Press. 2016;25(2):93-103. doi: 10.3109/08037051.2015.1116258. Epub 2015 Dec 1.

Abstract

Hypertension and type 2 diabetes mellitus (T2DM) are risk factors for cardiovascular disease. Dapagliflozin improves glycemic control and systolic blood pressure (SBP) in T2DM patients. This double-blind phase III study evaluated the effects of dapagliflozin on glycemic control and blood pressure in patients with inadequately controlled T2DM and hypertension, despite ongoing therapy with a renin-angiotensin system blocker. Patients were randomized to receive dapagliflozin 10 mg (n = 302) or placebo (n = 311) once daily for 12 weeks. Endpoints were change from baseline to week 12 in seated SBP and glycosylated hemoglobin (HbA1c); longitudinal repeated-measures analysis was performed. Additional endpoints included other hemodynamic measures, serum uric acid, fasting plasma glucose, body weight, blood lipids and heart rate. After 12 weeks, dapagliflozin-treated versus placebo-treated patients showed significant reductions in HbA1c (-0.6% vs -0.1%, p < 0.0001), mean seated SBP (-10.4 vs -7.3 mmHg, p = 0.0010) and mean 24 h ambulatory SBP (-9.6 vs -6.7 mmHg, p = 0.0043). Dapagliflozin also reduced body weight compared with placebo (-1.0 vs -0.3 kg). Dapagliflozin was well tolerated, with adverse events consistent with previous studies. Dapagliflozin improved glycemic control, and reduced SBP as well as body weight in patients with poorly controlled T2DM and hypertension.

Keywords: Blood pressure; dapagliflozin; diabetes; hypertension; sodium glucose cotransporter-2.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Antihypertensive Agents / therapeutic use*
  • Benzhydryl Compounds / therapeutic use*
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects*
  • Blood Pressure Determination
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Female
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin A / metabolism
  • Heart Rate / drug effects
  • Hemorheology
  • Humans
  • Hypertension / blood
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Renin-Angiotensin System / drug effects*
  • Systole
  • Uric Acid / blood

Substances

  • 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Benzhydryl Compounds
  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Uric Acid