GLP-1 Initiation Associated With Increase in Hypotensive Events in Patients With Hypertension

Recent data have shown that GLP-1 receptor agonist (RA) use is associated with a statistically significant increase in hypotension and related events among patients with preexisting hypertension.1

These data, presented at the Endocrine Society (ENDO) Annual Meeting 2026 in Chicago, Illinois, by Thomas Locascio, BS, a gap year intern at Northwestern Medicine, reflect the widespread implementation and prescription of GLP-1s for diabetes and obesity, as well as their potential outside of endocrinology.1,2

Due to their impact on cardiovascular, metabolic, and renal diseases, GLP-1s are prescribed for a long list of diseases across several conditions across the world. Despite this, data regarding their potential side effects are not complete. Gastrointestinal adverse events have been heavily studied since the drugs’ approval in the US – however, anecdotal evidence surrounding various adverse cardiovascular and renal outcomes continues to arise.2

“GLP-1 RAs are widely prescribed to treat metabolic cardiovascular renal disease,” Locascio and colleagues wrote. “While most side effects are mild and related to the gastrointestinal system, anecdotal evidence of clinically significant hypotension has been reported.”1

Locascio and colleagues structured the study around a within-person comparison, using a large-scale electronic health record database among outpatients prescribed GLP-1s including semaglutide, liraglutide, and tirzepatide. A total of 42,262 patients were included in the study, all of whom were aged ≥18 years and had taken ≥2 antihypertensive medication classes, as well as having document blood pressure measurements.1

Patients were evaluated for hypotensive events in the 6, 12, and 24 months after treatment initiation – these events were defined as a combined endpoint of syncope or near-syncope, dizziness, falls, documented systolic blood pressure ≤90 mmHg, new diagnosis of hypotension, or anti-hypotensive drug prescription. Additionally, the team conducted a sub-analysis to examine the frequency of changes in antihypertensive therapy, such as reductions in the number of treatments and decreases in dosage. According to the investigators, these changes would reflect averted hypotension. The sub-analysis included 40 patients randomly selected from the 12-month post-initiation cohort.1

Locascio and colleagues found that patients initiating GLP-1 RA treatment showed substantially higher rates of hypotensive events at all 3 timepoints. The incidence of hypotension rose from 8.7% at baseline to 10.2% at 6 months (P <.001), from 13.6% to 14.3% at 12 months (P = .003), and from 17.7% to 18.1% at 24 months (P = .061). Hypotensive events were most frequent among patients aged ≥65 years, as well as those diagnosed with type 2 diabetes mellitus (T2DM). Antihypertensive medication dosage was reduced, or the number of prescribed medications was decreased, in roughly 25% of patients.1

Locascio and colleagues ultimately concluded that GLP-1 RA usage is associated with a measurable and clinically significant increase in hypotensive-related events among patients with hypertension, increasing in frequency near the onset of treatment.1

“Future analyses should investigate the role of weight loss in greater detail,” Locascio and colleagues wrote. “Findings from these studies can be used to identify who is at greatest risk so that interventions can be implemented to mitigate these complications.”1

References

1. Eimer M, Chavez I, Locascio T. GLP1 Receptor Agonists and the Risk of Significant Hypotension Among Patients with Metabolic Cardiovascular Renal Disease: Too Much of A Good Thing? Abstract presented at the Endocrine Society (ENDO) Annual Meeting 2026, Chicago, IL. June 13-15.

2. Zhao X, Wang M, Wen Z, et al. GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects. Front Endocrinol (Lausanne). 2021;12:721135. Published 2021 Aug 23. doi:10.3389/fendo.2021.721135