Impact of Empagliflozin on Blood Pressure in Patients With Type 2 Diabetes Mellitus and Hypertension by Background Antihypertensive Medication

In the EMPA-REG BP trial, empagliflozin 10 mg and 25 mg once daily reduced glycohemoglobin, blood pressure (BP), and weight versus placebo in patients with type 2 diabetes mellitus and hypertension. Patients received placebo (n=271), empagliflozin 10 mg (n=276), or empagliflozin 25 mg (n=276) for 12 weeks (n=full analysis set). This present analysis investigated changes from baseline to week 12 in mean 24-hour systolic BP (SBP) and diastolic BP (DBP) in patients receiving 0, 1, or ≥2 antihypertensive medications and patients receiving/not receiving diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Compared with placebo, empagliflozin 10 mg and 25 mg reduced mean 24-hour SBP/DBP in patients receiving 0 (10 mg: −3.89/−2.58 mm Hg; 25 mg: −3.77/−2.45 mm Hg), 1 (10 mg: −4.74/−1.97 mm Hg; 25 mg: −4.27/−1.81 mm Hg), or ≥2 (10 mg: −2.36/−0.68 mm Hg; 25 mg: −4.17/−1.54 mm Hg) antihypertensives. The effect of empagliflozin was not significantly different between subgroups by number of antihypertensives for changes in SBP (interaction P value 0.448) or DBP (interaction P value 0.498). Empagliflozin reduced 24-hour mean SBP/DBP irrespective of diuretic or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, with no significant difference between subgroups by use/no use of diuretics (interaction P values 0.380 [systolic]; 0.240 [diastolic]) or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (interaction P values 0.900 [systolic]; 0.359 [diastolic]). In conclusion, in patients with type 2 diabetes mellitus and hypertension, empagliflozin for 12 weeks reduced SBP and DBP versus placebo, irrespective of the number of antihypertensives and use of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Clinical Trial Registration—URL: https://clinicaltrials.gov. Unique identifier: NCT01370005.

[1]  T. Mansfield,et al.  Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin–angiotensin system blockade , 2016, Blood pressure.

[2]  I. Tikkanen,et al.  Potential role of sodium glucose cotransporter 2 inhibitors in the treatment of hypertension , 2016, Current opinion in nephrology and hypertension.

[3]  B. Zinman,et al.  Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. , 2015, The New England journal of medicine.

[4]  C. Cannon,et al.  Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes , 2015, Diabetes, obesity & metabolism.

[5]  M. Cooper,et al.  4B.01: CONTRASTING INFLUENCES OF RENAL FUNCTION ON BLOOD PRESSURE AND HBA1C REDUCTIONS WITH EMPAGLIFLOZIN IN PATIENTS WITH TYPE 2 DIABETES AND HYPERTENSION , 2015, Journal of hypertension.

[6]  G. Mancia,et al.  Clinical value of ambulatory blood pressure: evidence and limits. , 2015, Circulation research.

[7]  B. Zinman,et al.  SGLT-2 inhibitors and cardiovascular risk: Proposed pathways and review of ongoing outcome trials , 2015, Diabetes & vascular disease research.

[8]  R. Townsend,et al.  SGLT2 inhibitors: their potential reduction in blood pressure. , 2015, Journal of the American Society of Hypertension : JASH.

[9]  I. Tikkanen,et al.  Empagliflozin Reduces Blood Pressure in Patients With Type 2 Diabetes and Hypertension , 2014, Diabetes Care.

[10]  D. Lorber.  Importance of cardiovascular disease risk management in patients with type 2 diabetes mellitus , 2014, Diabetes, metabolic syndrome and obesity : targets and therapy.

[11]  H. Häring,et al.  Empagliflozin as Add-On to Metformin in Patients With Type 2 Diabetes: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial , 2014, Diabetes Care.

[12]  A. Mithal,et al.  Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. , 2014, The lancet. Diabetes & endocrinology.

[13]  Jackson T. Wright,et al.  2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). , 2014, JAMA.

[14]  C. Kovacs,et al.  Empagliflozin improves glycaemic and weight control as add‐on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes: a 24‐week, randomized, placebo‐controlled trial , 2014, Diabetes, obesity & metabolism.

[15]  U. Broedl,et al.  The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus , 2014, Cardiovascular Diabetology.

[16]  F. Wolf,et al.  Standards of Medical Care in Diabetes—2016 Abridged for Primary Care Providers , 2016, Clinical Diabetes.

[17]  M. Roden,et al.  Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. , 2013, The lancet. Diabetes & endocrinology.

[18]  H. Häring,et al.  Empagliflozin as Add-on to Metformin Plus Sulfonylurea in Patients With Type 2 Diabetes , 2013, Diabetes Care.

[19]  Ann D Colosia,et al.  Prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in observational studies: a systematic literature review , 2013, Diabetes, metabolic syndrome and obesity : targets and therapy.

[20]  Jeroen J. Bax,et al.  2007 ESH-ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). , 2007, Blood pressure.

[21]  S. Saydah,et al.  The Prevalence of Meeting A1C, Blood Pressure, and LDL Goals Among People With Diabetes, 1988–2010 , 2013, Diabetes Care.

[22]  T. Heise,et al.  Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks' treatment with empagliflozin once daily in patients with type 2 diabetes , 2013, Diabetes, obesity & metabolism.

[23]  Michael Böhm,et al.  2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). , 2007, Journal of hypertension.

[24]  S. Inzucchi,et al.  Erratum to: Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) , 2013, Diabetologia.

[25]  D. Matthews,et al.  Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach , 2012, Diabetes Care.

[26]  D. Matthews,et al.  Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach , 2012, Diabetes Care.

[27]  S. Yusuf,et al.  Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) , 2011, Circulation.

[28]  D. Berney,et al.  Cushing syndrome secondary to a thymic carcinoid tumor due to multiple endocrine neoplasia type 1. , 2011, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[29]  Irl B Hirsch,et al.  American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. , 2011, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[30]  N. Perrier.  The parathyroid glands: what the endocrine surgeon should know. , 2011, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[31]  M. Vandervoort,et al.  Barriers to Blood Pressure Control: A STITCH Substudy , 2011, The Journal of Clinical Hypertension.

[32]  M. Woodward,et al.  Lowering blood pressure reduces renal events in type 2 diabetes. , 2009, Journal of the American Society of Nephrology : JASN.

[33]  Keith D. Smith,et al.  American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of menopause. , 2011, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[34]  David V. Power,et al.  Standards of Medical Care in Diabetes: Response to position statement of the American Diabetes Association , 2006 .

[35]  Y. Jang,et al.  Standards of Medical Care in Diabetes-2010 by the American Diabetes Association: Prevention and Management of Cardiovascular Disease , 2010 .

[36]  G. Mancia,et al.  Systolic and diastolic blood pressure control in antihypertensive drug trials. , 2002, Journal of hypertension.