Effect of incretin-based therapies on blood pressure: a systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: Modest but clinically meaningful BP reduction; dual agonists: SBP -5.1 mmHg, triple agonists: SBP -6.6 mmHg

• Primary Outcome: Systolic blood pressure reduction of 3.4 mmHg (95% CI 2.8-4.0) with GLP-1 receptor agonists

• Nnt Or Sensitivity: 18% mortality reduction (RR 0.82, 95% CI 0.76-0.90); weight loss correlation with BP reduction

• Confidence Interval: 95% CI 2.8-4.0 mmHg for SBP reduction with GLP-1 RAs

Clinical Application

High feasibility given PBS availability of semaglutide and other GLP-1 agonists for diabetes and obesity management Aligns with RACGP obesity management guidelines; supports PBS criteria for incretin therapies; relevant given Australia's obesity epidemic affecting 67% of adults Australian adults with obesity or overweight, particularly those with diabetes or cardiovascular risk factors

Abstract

AIMS: Hypertension and obesity frequently coexist and synergistically increase cardiovascular (CV) risk. Incretin-based therapies with glucagon-like peptide-1 receptor agonists (GLP-1-RAs), gastric inhibitory polypeptide (GIP)/GLP1-RAs, and glucagon/GIP/GLP-1RAs lead to substantial weight loss. However, their antihypertensive efficacy and safety profile have not been comprehensively quantified. Our study aimed to evaluate the effects of incretin-based therapies on office systolic blood pressure (BP) (SBP), diastolic BP (DBP), all-cause mortality, and key safety outcomes, i.e. hypoglycaemia and pancreatitis episodes, in adults with overweight or obesity. METHODS AND RESULTS: We searched PubMed, EMBASE, and ClinicalTrial.gov from inception to 30 April 2024 for randomized controlled trials (RCTs) comparing incretin-based therapy with placebo and ≥1 month of follow-up. The primary outcome was change in SBP; secondary outcomes were change in DBP, all-cause mortality, hypoglycaemia, and pancreatitis. Random effects meta-analyses generated mean differences (MDs) or risk ratios (RRs) along with 95% confidence intervals (CIs). Heterogeneity was explored with I2 statistics, subgroup analyses, and meta-regression. Eighty-five RCTs encompassing 90 977 participants (median follow-up time 8 months) met the eligibility criteria. GLP1-RAs reduced SBP by 3.4 mmHg (95% CI 2.8-4.0) and DBP by 0.9 mmHg (95% CI 0.5-1.2). A higher weight loss was significantly associated with a greater reduction in BP. The most significant BP reduction was associated with dual (SBP 5.1 mmHg; DBP 1.8 mmHg) and triple (SBP 6.6 mmHg; DBP 2.1 mmHg) receptor agonists. All-cause mortality was reduced by 18% (RR 0.82, 95% CI 0.76-0.90). Incretin-based therapy did not increase the risk of hypoglycaemia (RR 1.05, 95% CI 0.83-1.33) or pancreatitis (RR 0.84, 95% CI 0.61-1.15). CONCLUSION: Incretin-based therapy led to a modest but clinically meaningful BP reduction and lower all-cause mortality in adults with overweight or obesity, without excess in hypoglycaemia or pancreatitis episodes. There was a significant association between weight loss and the reduction in SBP and DBP. Dual and triple agonists exhibited the most pronounced antihypertensive effect. These findings support the use of incretin-based therapies as part of an integrated and multidisciplinary approach to managing obesity and hypertension, with multiple agonists showing particular promise. Our findings also underscore the need for long-term RCTs to clarify weight-independent mechanisms and the durability effect of BP reduction. Incretin-based therapy, now widely used for weight loss, also modestly reduces blood pressure and mortality, providing an additional health benefit to people with obesity or diabetes.Across 85 clinical trials (more than 90 000 adults), incretin-based therapy lowered systolic blood pressure by about 3 mmHg; the most significant falls occurred with the dual and triple agonists, and every kilogram lost made the reduction larger.Incretin-based therapy use was associated with an 18% lower mortality, with no increase in hypoglycaemia or pancreatitis episodes, supporting their safe dual role in weight control and cardiovascular protection.

References

1. 1.Basile, C., Merolla, A., Mancusi, C., De Luca, C., Fucile, I., Canonico, M. E., Giugliano, G., Orso, F., Morisco, C., & Esposito, G. (2026). Effect of incretin-based therapies on blood pressure: a systematic review and meta-analysis. European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwaf560