Effect of GLP-1 mimetics on blood pressure and relationship to weight loss and glycemia lowering: results of a systematic meta-analysis and meta-regression.

BACKGROUND: Incretin therapies such as glucagon-like peptide 1 (GLP-1) agonists are commonly used for the treatment of type 2 diabetes mellitus. GLP-1 mimetics, besides improving glycemic control, have been shown to influence multiple pathways regulating blood pressure (BP). We investigated the GLP-1 analogs effects on BP from published randomized studies using a meta-analytic approach. METHODS: Thirty-three trials (12,469 patients) that assessed the efficacy of GLP-1 analogs on glycemic control (HbA1C) over 12-56 weeks that met additional criteria, including the availability of standardized sitting BP assessment and weight parameters, were identified. Comparator therapy included oral antiglycemic drugs or placebo. The weighted mean difference (WMD) in systolic BP (SBP) change was calculated using a random-effects model after performing a test for heterogeneity. RESULTS: Forty-one percent of patients were treated with liraglutide (0.3-3mg once daily), whereas 59% were treated with exenatide (5-10 µg twice daily or 2mg weekly). GLP-1 treatment achieved a greater SBP reduction than comparator therapy (WMD = 2.22mm Hg; 95% confidence interval (CI) = -2.97 to -1.47). In the pooled analysis, GLP-1 had beneficial effects on weight loss (WMD = -2.56kg; 95% CI = -3.12 to -2.00), HbA1c reduction (WMD = -0.41%; 95% CI = -0.78 to -0.04) but was associated with a heart rate increase (WMD = 1.30 bpm; 95% CI = 0.26-2.33). In a separate meta-regression analysis, the degree of SBP change was not related to baseline BP, weight loss, or improvement in HbA1C. CONCLUSIONS: This meta-analysis provides evidence that GLP-1 analogs reduce sitting SBP. These findings may support potentially favorable long-term cardiovascular outcomes.