The blood pressure-lowering property of subcutaneous semaglutide: a systematic review, meta-analysis, and meta-regression.

Purpose: Semaglutide is a glucagon-like peptide (GLP1) receptor agonist with unprecedented weight-lowering and anti-hyperglycemic properties. Recent clinical trials reported that subcutaneous semaglutide can modulate blood pressure; however, its effect on blood pressure widely varied in different studies and different subgroups of patients.

Methods: PubMed, Web of Science, Scopus, and the Cochrane Library were systematically searched from the inception to July 18, 2024. Due to high heterogeneity, a random-effects model was adopted to pool data.

Results: Twenty clinical trials with 15,312 participants in the placebo group and 18,231 participants in the semaglutide group were included in this study. Subcutaneous semaglutide significantly decreased both systolic (WMD - 3.71 mmHg, 95% CI (-4.29, -3.13), I²: 50.2%) and diastolic (WMD - 1.10 mmHg, 95% CI (-1.58, -0.63), I²: 69.7%) blood pressure. Subgroup analyses indicated that the blood pressure-lowering property of subcutaneous semaglutide was greater among patients without diabetes, with lower baseline hemoglobin A1c (HbA1c), baseline body mass index (BMI) greater than 35 kg/m², dose of semaglutide more than 1 mg/week, baseline systolic blood pressure equal or less than 130 mmHg, weight loss greater than 10 kg, and BMI reduction greater than 3 kg/m². In addition, a treatment length of 50 to 100 weeks was associated with greater blood pressure-lowering effects in subgroup analysis. After adjusting for other factors, meta-regression revealed that placebo-adjusted weight change was independently correlated with the effect of semaglutide on systolic and diastolic blood pressure.

Conclusion: Subcutaneous semaglutide can significantly decrease systolic and diastolic blood pressure, particularly in selected groups of patients.