Effects of empagliflozin on blood pressure and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes

R Chilton, I Tikkanen, C P Cannon, S Crowe, H J Woerle, U C Broedl, O E Johansen, R Chilton, I Tikkanen, C P Cannon, S Crowe, H J Woerle, U C Broedl, O E Johansen

Abstract

Aims: To determine the effects of empagliflozin on blood pressure (BP) and markers of arterial stiffness and vascular resistance in patients with type 2 diabetes mellitus (T2DM).

Methods: We conducted a post hoc analysis of data from a phase III trial in patients with T2DM and hypertension receiving 12 weeks' empagliflozin and four phase III trials in patients with T2DM receiving 24 weeks' empagliflozin (cohort 1, n = 823; cohort 2, n = 2477). BP was measured using 24-h BP monitoring (cohort 1) or seated office measurements (cohort 2).

Results: Empagliflozin reduced systolic BP (SBP) and diastolic BP in both cohorts (p < 0.001 vs placebo), without increasing heart rate. Empagliflozin reduced pulse pressure (PP; adjusted mean difference vs placebo cohort 1: -2.3 mmHg; cohort 2: -2.3 mmHg), mean arterial pressure (MAP; cohort 1, -2.3 mmHg; cohort 2, -2.1 mmHg) and double product (cohort 1, -385 mmHg × bpm; cohort 2, -369 mmHg × bpm) all p < 0.001 vs placebo. There was a trend towards a reduction in the ambulatory arterial stiffness index (AASI) with empagliflozin in cohort 1 (p = 0.059 vs placebo). AASI was not measured in cohort 2. Subgroup analyses showed that there were greater reductions in PP with increasing baseline SBP in cohort 1 (p = 0.092). In cohort 2, greater reductions in MAP were achieved in patients with higher baseline SBP (p = 0.027) and greater reductions in PP were observed in older patients (p = 0.011).

Conclusions: Empagliflozin reduced BP and had favourable effects on markers of arterial stiffness and vascular resistance.

Keywords: SGLT2 inhibitor; cardiovascular disease; phase III study; type 2 diabetes.

© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Changes in markers of arterial stiffness and vascular resistance. (A) Change from baseline in pulse pressure (PP) at week 12 in cohort 1 and week 24 in cohort 2 [analysis of covariance (ancova) using last observation carried forward (LOCF)]. (B) Change from baseline in mean arterial pressure (MAP) at week 12 in cohort 1 and week 24 in cohort 2 (ancova, LOCF). (C) Change from baseline in double product (DP) or rate pressure product (RPP) at week 12 in cohort 1 and week 24 in cohort 2 (ancova, LOCF). (D) Change from baseline in ambulatory arterial stiffness index (AASI) at week 12 in cohort 1. Data are adjusted mean ± standard error (s.e.) in the full analysis set. In cohort 1, measurements were based on mean 24‐h ABPM and in cohort 2, they were based on seated office measurements.
Figure 2
Figure 2
Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP) by subgroups of baseline age. (A) SBP, DBP, PP and MAP at baseline and at week 12 in cohort 1. (B) SBP, DBP, PP and MAP at baseline at week 24 in cohort 2. Baseline data are mean ± standard error (s.e.), week 12 or 24 data are adjusted mean ± s.e. based on analysis of covariance (ancova) in the full analysis set using last observation carried forward (LOCF) imputation. In cohort 1, measurements were based on mean 24‐h ambulatory blood pressure monitoring (ABPM) and in cohort 2, they were based on seated office measurements. ***p < 0.001, **p < 0.01 and *p < 0.05 for adjusted mean differences for empagliflozin versus placebo in change from baseline based on ancova with LOCF imputation.
Figure 3
Figure 3
Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP) by sex. (A) SBP, DBP, PP and MAP at baseline and at week 12 in cohort 1. (B) SBP, DBP, PP and MAP at baseline and at week 24 in cohort 2. Baseline data are mean ± standard error (s.e.), week 12 or 24 data are adjusted mean ± s.e. based on analysis of covariance (ancova) in the full analysis set using last observation carried forward (LOCF) imputation. In cohort 1, measurements were based on mean 24‐h ambulatory blood pressure monitoring (ABPM) and in cohort 2, they were based on seated office measurements. ***p < 0.001, **p < 0.01 and *p < 0.05 for adjusted mean differences for empagliflozin versus placebo in change from baseline based on ancova with LOCF imputation.
Figure 4
Figure 4
Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and mean arterial pressure (MAP) by subgroups of baseline SBP. (A) SBP, DBP, PP and MAP at baseline and at week 12 in cohort 1. (B) SBP, DBP, PP and MAP at baseline and at week 24 in cohort 2. Baseline data are mean ± standard error (s.e.), week 12 or 24 data are adjusted mean ± s.e. based on analysis of covariance (ancova) in the full analysis set using last observation carried forward (LOCF) imputation. In cohort 1, measurements were based on mean 24‐h ambulatory blood pressure monitoring (ABPM) and in cohort 2, they were based on seated office measurements. ***p < 0.001, **p < 0.01 and *p < 0.05 for adjusted mean differences for empagliflozin versus placebo in change from baseline based on ancova with LOCF imputation.

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