The effect of subcutaneous semaglutide injection on blood pressure: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Hypertension remains a leading contributor to cardiovascular disease globally. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), reduces blood pressure in clinical trials, but the consistency and magnitude of this effect across populations is unclear. We conducted a systematic review and meta-analysis of placebo-controlled randomized trials reporting blood pressure changes in patients receiving subcutaneous semaglutide. MEDLINE, Web of Science, and Embase were searched through December 2025. Pooled weighted mean differences with 95% confidence intervals were calculated using random-effects inverse-variance models. Cochrane's RoB 2.0 assessed risk of bias, and the Grading of recommendations Assessment Development and Evaluation (GRADE) approach was used to evaluate the certainty of the evidence. Our meta-analysis included seven trials with approximately 20,000 patients. Semaglutide reduced systolic blood pressure (SBP) significantly compared with placebo across 11 arms (20,011 participants): weighted mean difference -3.46 mmHg (95% CI: -4.44 to -2.49; I2 = 29.5%; high certainty of evidence). A modest reduction in diastolic blood pressure (DBP) was also observed (-0.56 mmHg, 95% CI: -0.82 to -0.29; I2 = 0.0%; moderate certainty of evidence). However, sensitivity analysis revealed that the DBP effect was dependent on a single large study, with loss of significance upon its exclusion. Subcutaneous semaglutide produces meaningful SBP reduction across diverse patient populations, with minimal DBP changes. Blood pressure improvement represents one component of semaglutide's cardiometabolic benefits.

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