Effect of tirzepatide and semaglutide on blood pressure: A systematic review and meta-analysis

In this meta-analysis of 32 RCTs in 47,332 people, tirzepatide was linked to fewer hypertension-related adverse events but more hypotension-related events, especially at higher doses; semaglutide showed no significant association with either. The authors say these distinct blood pressure safety profiles may support individualized treatment decisions.

Meta-analysis — Systematic review and meta-analysis of RCTs. Population: Patients with type 2 diabetes mellitus or obesity. Sample size: 47,332 participants. Interventions: Tirzepatide; Semaglutide.

Pooled analyses of 32 RCTs (47,332 participants) found tirzepatide was associated with a lower risk of hypertension-related events (RR = 0.40, 95% CI [0.26-0.60]; p < 0.001) and a higher risk of hypotension-related events (RR = 2.45, 95% CI [1.35-4.45]; p = 0.003). The hypotension risk was stronger at higher doses (RR = 2.58, 95% CI [1.38-4.81]; p = 0.003). Semaglutide was not significantly associated 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), though potential protective signals were observed in high-dose subgroups.

This paper matters to researchers studying semaglutide because it places semaglutide's blood-pressure safety profile against tirzepatide in a large pooled analysis, showing no significant hypertension or hypotension signal overall. It does not establish mechanisms, long-term cardiovascular outcomes, or whether semaglutide lowers blood pressure in individual patients.

Key findings

• Tirzepatide was associated with a lower risk of hypertension-related events (RR = 0.40, 95% CI [0.26-0.60]; p < 0.001).
• Tirzepatide was associated with an increased risk of hypotension-related events (RR = 2.45, 95% CI [1.35-4.45]; p = 0.003).
• At higher tirzepatide doses, the hypotension risk was higher (RR = 2.58, 95% CI [1.38-4.81]; p = 0.003).
• Semaglutide showed no significant association with hypertension-related events (RR = 0.81, 95% CI [0.57-1.15]; p = 0.233).
• Semaglutide showed no significant association with hypotension-related events (RR = 1.39, 95% CI [0.81-2.36]; p = 0.232).

Limitations

• Adverse-event definitions and ascertainment may differ across the included RCTs.
• The pooled estimates are trial-level and do not use individual-patient data.
• Follow-up durations and baseline blood pressure likely varied across trials and were not accounted for in the abstract.
• Direct head-to-head comparisons between tirzepatide and semaglutide are not described in the abstract.

The record

• Journal: Endocrine 91(1): 275
• Published: 2026-08-15
• PMID: 42603240 — DOI: 10.1007/s12020-026-04757-7
• MeSH terms: Humans, Hypertension, Diabetes Mellitus, Type 2, Obesity, Blood Pressure, Glucagon-Like Peptides, Randomized Controlled Trials as Topic, Tirzepatide, Semaglutide
• Funding: National Natural Science Foundation of China
• Author countries: China

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.

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