Reductions in systolic blood pressure with liraglutide in patients with type 2 diabetes: insights from a patient-level pooled analysis of six randomized clinical trials

Abstract

Aims: To quantify the effect of liraglutide on systolic blood pressure (SBP) and pulse in patients with type 2 diabetes (T2D), and assess the influence of covariates on observed SBP reductions.

Methods: A patient-level pooled analysis of six phase 3, randomized trials was conducted.

Results: The analysis included 2792 randomized patients. In the intention-to-treat population (n=2783), mean [±SE] SBP reductions from baseline with liraglutide 1.2 mg (2.7 [0.8] mmHg) and 1.8 mg (2.9 [0.7] mmHg) once daily were significantly greater than with placebo (0.5 [0.9] mmHg; P=0.0029 and P=0.0004, respectively) after 26 weeks, and were evident after 2 weeks. Liraglutide was also associated with significantly greater SBP reductions than glimepiride and, at a dose of 1.8 mg, insulin glargine and rosiglitazone. SBP reductions with liraglutide weakly correlated with weight loss (Pearson's correlation coefficient: 0.08-0.12; P≤0.0148). No dependence of these reductions on concomitant antihypertensive medications was detected (P=0.1304). Liraglutide 1.2 and 1.8 mg were associated with mean increases in pulse of 3 beats per minute (bpm), versus a 1 bpm increase with placebo (P<0.0001 for each dose versus placebo).

Conclusions: Liraglutide reduces SBP in patients with T2D, including those receiving concomitant antihypertensive medication.

Trial registration: ClinicalTrials.gov NCT00294723 NCT00318422 NCT00318461 NCT00331851 NCT00333151 NCT00518882.

Keywords: Blood pressure; Hypertension; Liraglutide; Type 2 diabetes.

Conflict of interest statement

Conflicts of interest: V.F. has received advisory board honoraria and speakers’ bureau honoraria from Novo Nordisk, and his institution has received research funding from Novo Nordisk; V.F. is currently Editor-in-Chief of this journal. J.H.D. or his institution has received advisory board honoraria and speakers’ bureau honoraria from Novo Nordisk, and his institution has received research funding from Novo Nordisk. R.H.’s institution has received research funding from Novo Nordisk. J.P. has received consultancy fees from Novo Nordisk. M.D. and H.T. are currently employed by and own shares in Novo Nordisk A/S. These analyses were sponsored by Novo Nordisk A/S, Copenhagen, Denmark. All authors discussed the data, edited the manuscript for important intellectual content, and approved the version for publication. H.T carried out the statistical analyses.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1. Change in systolic blood pressure (SBP) with liraglutide versus placebo and active comparators

Diamonds indicate liraglutide–placebo or liraglutide–active comparator estimated treatment differences in change in SBP from baseline (analysis of covariance models) for pooled data from LEAD-1–6. The width of the horizontal lines indicates 95% confidence intervals for each estimated treatment difference. LS, least squares; SBP, systolic blood pressure.

Fig. 2. Change in systolic blood pressure (SBP) over time

Data are last observation carried forward for the intention-to-treat population, and expressed as least squares means ± 95% confidence interval.