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 −1.84mmHg (95% CI: −3.48 to −0.20) to −4.60mmHg (95% CI: −7.18 to −2.03). Compared with placebo, a reduction in diastolic blood pressure was detected significantly only for exenatide-10μg-twice-daily (−1.08mmHg, 95% CI: −1.78 to −0.33). Exenatide (2mg once weekly), liraglutide 1.2mg once daily), and liraglutide (1.8mg 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-10μg-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.