GLP-1s Tied to Higher Risk for Dizziness, Fainting for Some

 Hypotension-related events increased after initiation of GLP-1s in patients taking multiple antihypertensive medications, researchers found. Patients aged 65 years or older and those with type 2 diabetes were most at risk.

“Hypotension is the most dreaded potential side effect of treating hypertension and actually far more dangerous,” study co-author Micah Eimer, MD, Northwestern University Feinberg School of Medicine in Glenview, Illinois, said in a statement. “People die from that. You can hit your head, or you can crash your car or break your hip. So it’s a very bad outcome when it happens.”

When he became aware that some of his patients on GLP-1s were complaining of lightheadedness, dizziness, and fainting, Eimer decided to investigate. His team’s study was presented at ENDO 2026: The Endocrine Society Annual Meeting.

‘Potential to Do Harm’

The researchers retrospectively analyzed the electronic health records of 42,262 patients taking at least two antihypertensive medication classes and evaluated these patients for hypotensive events in the 6, 12, and 24 months following GLP-1 initiation.

Hypotensive events were defined as a combined endpoint of a new diagnosis of hypotension, syncope or near syncope, dizziness, falls, documented systolic blood pressure ≤ 90 mm Hg, or antihypotensive drug prescription.

At 6 months, hypotensive events increased from 8.7% to 10.2%. At 12 months, the rate rose from 13.6% to 14.3%. At 24 months, the difference was 17.7%-18.1%.

Adults aged 65 years or older accounted for 53% of hypotensive events despite representing only 37% of the study population. Patients with type 2 diabetes made up 75% of those experiencing hypotensive episodes, but only 63% of the overall cohort.

In a subset analysis of 40 randomly selected patients, the researchers found that approximately 25% had their antihypertensive medications reduced in dose or number during the study period.

Secondary analyses showed that weight loss alone did not explain the increased risk.

“The predominant reason [for the hypotensive events] is likely due to weight loss, which is known to lower blood pressure,” Eimer told Medscape Medical News. “Even 5% weight loss will result in significant blood pressure lowering.”

“But other mechanisms that might be at play include potentiation of certain blood pressure medications by the GLP-1s, dehydration caused by GLP-1s, direct blood pressure-lowering effects by relaxing blood vessels, decreasing sympathetic nerve activity, and promoting sodium excretion in the urine,” he said.

Meanwhile, he added, “I’m just saying, let’s watch out for hypotensive events in select patients because I think there’s the potential to do harm. I am particularly worried about the risk to patients who obtain GLP-1s without direct and ongoing clinical supervision.”

‘A Prompt for Vigilance’

Sara Ghoneim, MD, an inflammatory bowel disease specialist at Massachusetts General Hospital in Boston, and a spokesperson for the American Gastroenterological Association, commented on the study for Medscape Medical News.

“The findings are biologically plausible and consistent with clinical experience,” she said. “GLP-1 receptor agonists lower blood pressure through several converging mechanisms, including weight loss, natriuresis, improved endothelial function, and possibly direct vascular effects. When you add a steadily falling blood pressure to a fixed regimen of two or more antihypertensives, the arithmetic predicts exactly what this study found — a drift toward hypotension as therapy continues.”

“Many of us have seen patients on semaglutide or tirzepatide who become lightheaded, orthostatic, or frankly hypotensive months into treatment, often prompting us to peel back their antihypertensive agents.”

However, Ghoneim flagged several study limitations. As a retrospective observational study, it establishes association, not causation, and is vulnerable to confounding and ascertainment bias, she said. “Patients on a new drug are seen and measured more often, which can inflate the apparent detection of dizziness, falls, or low readings.”

The composite endpoint is broad, she noted. “It lumps a coded hypotension diagnosis together with nonspecific symptoms like dizziness and falls, so the headline incidence is sensitive to how those soft outcomes are counted.”

Furthermore, “the absolute effect sizes are modest and the 24-month difference lost significance [and] the medication-change subanalysis was based on only 40 randomly selected patients, which is too small to anchor a 25% figure firmly.”

Nevertheless, she said, this is something clinicians should be alerted to, “though as a prompt for vigilance rather than alarm. When you start a GLP-1 in a patient already on multiple antihypertensives, anticipate that their blood pressure may fall, monitor more closely in the first months, counsel about orthostatic symptoms and fall risk — especially in older adults and those with type 2 diabetes — and be ready to de-prescribe antihypertensives proactively rather than waiting for syncope.”

“That’s already good practice,” she said. “This study reinforces why it matters.”

Eimer declared serving on the advisory board of Eli Lilly. Ghoneim declared having no conflicts of interest.

https://www.medscape.com/viewarticle/glp-1s-tied-higher-risk-dizziness-fainting-some-2026a1000kjq