Impact of GLP-1 receptor agonists on blood pressure, heart rate and hypertension among patients with type 2 diabetes: A systematic review and network meta-analysis

Abstract

Aims: To evaluate current evidence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood pressure, heart rate, and hypertension in patients with type 2 diabetes.

Methods: Medline, Embase, the Cochrane library, and the website www.clinicaltrials.gov were searched on April 5th, 2014. Randomized-controlled trials with available data were included if they compared GLP-1RAs with placebo and traditional antidiabetic drugs in patients with type 2 diabetes with duration ≥ 12 weeks. Weighted mean difference for blood pressure and heart rate, odds ratio (OR) for hypertension were calculated by random-effect model. Network meta-analysis was performed to supplement direct comparisons.

Results: Sixty trials with 14 treatments were included. Compared with placebo, insulin, and sulfonylureas, GLP-1RAs decreased systolic blood pressure with range from -1.84 mmHg (95% CI: -3.48 to -0.20) to -4.60 mmHg (95% CI: -7.18 to -2.03). Compared with placebo, a reduction in diastolic blood pressure was detected significantly only for exenatide-10 μg-twice-daily (-1.08 mmHg, 95% CI: -1.78 to -0.33). Exenatide (2 mg once weekly), liraglutide 1.2 mg once daily), and liraglutide (1.8 mg once daily) increased heart rate by 3.35 (95% CI: 1.23-5.50), 2.06 (95% CI: 0.43, 3.74), and 2.35 (95% CI: 0.94-3.76) beats/min versus placebo. This effect was evident compared with active control (range: 2.22-3.62). No significant association between incident hypertension and GLP-1RAs was detected, except for the association between exenatide-10 μg-twice-daily and sulfonylureas (OR, 0.40, 95% CI: 0.16, 0.82).

Conclusions: GLP-1RAs were associated with modest reduction on blood pressure, a slight increase in heart rate, yet no significant association with hypertension. Further investigation to explore mechanisms is warranted.

Keywords: Blood pressure; GLP-1 receptor agonists; Heart rate; Hypertension; Network meta-analysis; Type 2 diabetes.