research letter
Diabetes, Obesity and Metabolism 17: 805–808, 2015. © 2015 John Wiley & Sons Ltd
This study compared the blood pressure-lowering effect of ertugliflozin (1, 5, 25 mg), hydrochlorothiazide (HCTZ; 12.5 mg) and placebo in 194 patients with type 2 diabetes mellitus and hypertension for 4 weeks using ambulatory blood pressure monitoring. Endpoints (change from baseline to week 4) were: 24-h mean systolic blood pressure (SBP; primary); daytime, night-time, seated predose SBP, 24-h, daytime, night-time, seated predose diastolic blood pressure, 24-h urinary glucose excretion and fasting plasma glucose (FPG; secondary). Safety and tolerability were monitored. Significant decreases in placebo-corrected 24-h mean SBP (−3.0 to −4.0 mmHg) were recorded for all doses of ertugliflozin (for HCTZ, this was −3.2 mmHg). Daytime, but not night-time SBP was consistently reduced. Ertugliflozin produced dose-dependent significant decreases in FPG and increases in urinary glucose excretion. No notable changes in plasma renin activity or urinary aldosterone were seen. The most common adverse events were urinary tract infection, genital fungal infection, upper respiratory tract infection and musculoskeletal pain. Keywords: ambulatory blood pressure monitoring, ertugliflozin, PF-04971729, sodium-glucose co-transporter, type 2 diabetes mellitus Date submitted 12 December 2014; date of first decision 4 January 2015; date of final acceptance 27 April 2015
Introduction Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce renal glucose absorption, augment glucosuria [1,2] and reduce plasma glucose independently of insulin release, with concurrent beneficial effects on blood pressure and body weight [3–8]. Ertugliflozin (PF-04971729) is a selective SGLT2 inhibitor (half maximum inhibitory concentration: SGLT2, 0.877 nM; SGLT1, 1960 nM) [9], that increases urinary glucose excretion (UGE) and reduces fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and blood pressure. This study (NCT01096667) assessed the dose–response effect of ertugliflozin administered once daily for 4 weeks on systolic blood pressure (SBP) in adults with type 2 diabetes (T2DM) and hypertension using ambulatory blood pressure monitoring (ABPM) with hydrochlorothiazide (HCTZ) as a positive control.
Methods Study Design This study was conducted at 37 centres across India, Malaysia, Taiwan, Serbia and the USA. The doses of ertugliflozin selected were based on 50% of maximum inhibition of UGE predicted with doses of 2.5–3.0 mg (ED50 ) and Correspondence to: Neeta B. Amin, PharmD, CVMED Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Mail Stop 004-403, Cambridge, MA 02139, USA. E-mail: [email protected]
90% of maximum inhibition of UGE predicted at 25 mg (ED90 ). After screening, patients entered a run-in period of at least 3 (maximum 6) weeks, where agents that block the renin–angiotensin–aldosterone system (RAAS) were withdrawn and baseline re-established. Patients with inadequately controlled T2DM [HbA1c 7.0–10%; FPG
Diabetes, Obesity and Metabolism 17: 805–808, 2015. © 2015 John Wiley & Sons Ltd
This study compared the blood pressure-lowering effect of ertugliflozin (1, 5, 25 mg), hydrochlorothiazide (HCTZ; 12.5 mg) and placebo in 194 patients with type 2 diabetes mellitus and hypertension for 4 weeks using ambulatory blood pressure monitoring. Endpoints (change from baseline to week 4) were: 24-h mean systolic blood pressure (SBP; primary); daytime, night-time, seated predose SBP, 24-h, daytime, night-time, seated predose diastolic blood pressure, 24-h urinary glucose excretion and fasting plasma glucose (FPG; secondary). Safety and tolerability were monitored. Significant decreases in placebo-corrected 24-h mean SBP (−3.0 to −4.0 mmHg) were recorded for all doses of ertugliflozin (for HCTZ, this was −3.2 mmHg). Daytime, but not night-time SBP was consistently reduced. Ertugliflozin produced dose-dependent significant decreases in FPG and increases in urinary glucose excretion. No notable changes in plasma renin activity or urinary aldosterone were seen. The most common adverse events were urinary tract infection, genital fungal infection, upper respiratory tract infection and musculoskeletal pain. Keywords: ambulatory blood pressure monitoring, ertugliflozin, PF-04971729, sodium-glucose co-transporter, type 2 diabetes mellitus Date submitted 12 December 2014; date of first decision 4 January 2015; date of final acceptance 27 April 2015
Introduction Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce renal glucose absorption, augment glucosuria [1,2] and reduce plasma glucose independently of insulin release, with concurrent beneficial effects on blood pressure and body weight [3–8]. Ertugliflozin (PF-04971729) is a selective SGLT2 inhibitor (half maximum inhibitory concentration: SGLT2, 0.877 nM; SGLT1, 1960 nM) [9], that increases urinary glucose excretion (UGE) and reduces fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) and blood pressure. This study (NCT01096667) assessed the dose–response effect of ertugliflozin administered once daily for 4 weeks on systolic blood pressure (SBP) in adults with type 2 diabetes (T2DM) and hypertension using ambulatory blood pressure monitoring (ABPM) with hydrochlorothiazide (HCTZ) as a positive control.
Methods Study Design This study was conducted at 37 centres across India, Malaysia, Taiwan, Serbia and the USA. The doses of ertugliflozin selected were based on 50% of maximum inhibition of UGE predicted with doses of 2.5–3.0 mg (ED50 ) and Correspondence to: Neeta B. Amin, PharmD, CVMED Research Unit, Pfizer Worldwide Research and Development, 610 Main Street, Mail Stop 004-403, Cambridge, MA 02139, USA. E-mail: [email protected]
90% of maximum inhibition of UGE predicted at 25 mg (ED90 ). After screening, patients entered a run-in period of at least 3 (maximum 6) weeks, where agents that block the renin–angiotensin–aldosterone system (RAAS) were withdrawn and baseline re-established. Patients with inadequately controlled T2DM [HbA1c 7.0–10%; FPG
