A meta-analysis of 32 RCTs (47,332 participants) compared the blood pressure-related safety profiles of tirzepatide and semaglutide in patients with type 2 diabetes or obesity. Tirzepatide significantly reduced the risk of hypertension-related adverse events (RR 0.40) but increased the risk of dose-dependent hypotension (RR 2.45), whereas semaglutide demonstrated a neutral profile. These distinct hemodynamic effects highlight the need for individualized dosing and careful blood pressure monitoring, particularly in patients with low baseline readings.
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.
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.
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.
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.
