ORF04-03 - GLP1 Receptor Agonists and the Risk of Significant Hypotension Among Patients with Metabolic Cardiovascular Renal Disease: Too Much of A Good Thing?

Background: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are widely prescribed to treat metabolic cardiovascular renal disease (Met-CVRD). While most side effects are mild and related to the gastrointestinal system, anecdotal evidence of clinically significant hypotension has been reported.

Methods: A retrospective observational study consisting of a within-person comparison was conducted using a large-scale electronic health record database among outpatients prescribed the following GLP1-RAs: semaglutide, tirzepatide, and liraglutide. The sample included 42,262 patients aged 18 years or older who took at least two anti-hypertensive medication classes and had documented blood pressure measurements. These patients were evaluated for hypotensive events in the 6, 12, and 24 months following GLP1-RA initiation. Hypotensive events were defined as a combined endpoint of: new diagnosis of hypotension, syncope or near-syncope, dizziness, falls, documented systolic blood pressure ≤ 90 mm Hg, or anti-hypotensive drug prescription. A sub-analysis was performed to assess the frequency of changes in anti-hypertensive therapy, including both the reductions in the number of medications and decreases in medication dosage, which would suggest averted hypotension; this included 40 randomly selected participants from the 12-month post-initiation cohort. Regression models compared blood pressure changes among 54,682 patients treated with similar antihypertensive therapy with and without GLP1-RA prescriptions.


Results: Patients who initiated GLP-1RA demonstrated a significantly higher rate of hypotensive events at 6, 12, and 24 months. The incidence of hypotension increased from 8.7% to 10.2% at 6 months (p < 0.001), from 13.6% to 14.3% at 12 months (p = 0.003), and from 17.7% to 18.1% at 24 months (p = 0.061). Hypotensive-related episodes were most common among patients aged ≥65 years and those diagnosed with type 2 diabetes mellitus. The dosage of anti-hypertensive medication was reduced, or the number of prescribed antihypertensive medications was decreased, in approximately 25% of patients during this time. Accounting for weight change did not eliminate the strength of association.

Conclusions: GLP1-RA use is associated with a measurable increase in hypotensive-related events among patients with pre-existing hypertension, particularly near the onset of treatment. These associations were particularly pronounced among older patients and those with T2DM. Future analyses should investigate the role of weight loss in greater detail. Findings from these studies can be used to identify who is at greatest risk so that interventions can be implemented to mitigate these complications.