Endocrine. 2026 Aug 15;91(1):275. doi: 10.1007/s12020-026-04757-7.
ABSTRACT
PURPOSE: Tirzepatide and semaglutide are widely used for type 2 diabetes mellitus (T2DM) and obesity. However, the blood pressure-related adverse event profiles associated with tirzepatide and semaglutide remain unclear. This study systematically evaluated hypertension- and hypotension-related treatment-emergent adverse events (TEAEs) that occurred when using tirzepatide and semaglutide for the treatment of T2DM or obesity.
METHODS: A comprehensive search was performed in PubMed, Scopus, Web of Science, Embase, CENTRAL, and ClinicalTrials.gov from inception to September 26, 2025. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model, with subgroup analyses performed.
RESULTS: This meta-analysis of 32 randomized controlled trials (RCTs), enrolling 47,332 participants, revealed distinct differences in the blood pressure-related safety profiles of tirzepatide and semaglutide. Tirzepatide was associated with a lower risk of hypertension-related events (RR = 0.40, 95% CI [0.26-0.60]; p < 0.001). This potent antihypertensive effect was accompanied by an increased risk of hypotension-related events (RR = 2.45, 95% CI [1.35-4.45]; p = 0.003), particularly at higher doses (RR = 2.58, 95% CI [1.38-4.81]; p = 0.003). Semaglutide exhibited a relatively neutral blood pressure-related safety profile, showing no significant association with either hypertension-related events (RR = 0.81, 95% CI [0.57-1.15]; p = 0.233) or hypotension-related events (RR = 1.39, 95% CI [0.81-2.36]; p = 0.232), although potential protective signals were observed in high-dose subgroups.
CONCLUSION: Tirzepatide reduces hypertension-related adverse events but increases dose-dependent hypotension risk in patients with T2DM or obesity. These distinct hemodynamic safety profiles support individualized treatment decisions based on baseline blood pressure and cardiometabolic risk.
PMID:42603240 | DOI:10.1007/s12020-026-04757-7