GLP-1 Receptor Agonists Linked to Elevated Rates of Hypotensive Events in Patients on Antihypertensives
核心洞察
A large-scale analysis found GLP-1 users on antihypertensives had higher hypotensive event rates vs. nonusers at 6 months (10.2% vs. 8.7%; P < .001) and 12 months (14.3% vs. 13.6%; P = .003).
Patients aged 65 and older accounted for 53% of hypotensive events despite representing 37% of the study population; those with type 2 diabetes (搜索) made up 75% of events.
Weight loss alone did not explain the increased hypotension (搜索) risk, suggesting other mechanisms such as direct blood pressure-lowering effects or autonomic dysfunction may be involved.
CHICAGO — In patients being treated for hypertension (搜索), those taking a GLP-1 receptor (搜索) agonist experienced higher rates of hypotensive events compared with those not taking one, according to findings presented at ENDO 2026, the Endocrine Society's annual meeting. The study, drawn from a large-scale electronic health record database, raises important safety considerations for a drug class that has seen explosive growth in clinical use.
Micah J. Eimer, MD, associate chief medical officer in the division of cardiology at Northwestern Medicine and senior author of the study, launched the investigation after observing a pattern in his own practice. "I began to notice multiple patients in clinic who were started on GLP-1s (by me and others) who were complaining of lightheadedness, dizziness and fainting. They had low blood pressure on my examination," Eimer said. "Hypotension (搜索) is the most dreaded potential side effect of treating hypertension (搜索) and actually far more dangerous. The results were confirmatory to our clinical suspicion."
Study Design and Population
Eimer and colleagues analyzed blood pressure changes in 54,682 patients taking at least two medications for hypertension (搜索), drawn from a large-scale electronic health record database. Patients were stratified by whether or not they were taking a GLP-1 receptor (搜索) agonist — liraglutide (Victoza/Saxenda, Novo Nordisk), semaglutide (Ozempic/Wegovy, Novo Nordisk) or tirzepatide (Mounjaro/Zepbound, Eli Lilly).
The research team tracked hypotensive events — which included dizziness, fainting, falls, low blood pressure diagnoses, systolic blood pressure readings below 90 mm Hg, and prescriptions for medications used to treat hypotension (搜索) — over six, 12, and 24 months after patients started GLP-1 therapy.
Key Findings: Elevated Hypotension (搜索) Rates
Compared with nonusers, GLP-1 users had higher rates of hypotensive events at 6 months (10.2% vs. 8.7%; P < .001), 12 months (14.3% vs. 13.6%; P = .003), and 24 months (18.1% vs. 17.7%; P = .061), the researchers found.
The increased risk was particularly pronounced in certain subgroups. Adults aged 65 and older accounted for 53% of hypotensive events despite representing only 37% of the study population. Patients with type 2 diabetes (搜索) made up 75% of those experiencing hypotensive episodes but only 63% of the overall cohort.
"Older patients are just more susceptible to changes in blood pressure. Older patients have stiffer arteries, more blockages in their arteries and may get much more symptomatic from a change in blood pressure," Eimer explained. "The other thing is that patients with diabetes may have autonomic dysfunction, that's a known complication of diabetes, so they don't regulate blood pressure well."
Weight Loss Does Not Fully Account for the Risk
In secondary analyses, the scientists found that accounting for weight change did not affect the relationship between hypotension (搜索) and GLP-1 use. This suggests mechanisms beyond weight reduction are contributing to the observed blood pressure drops.
"Weight loss does not fully account for the observed hypotension (搜索)," Eimer said. "Other mechanisms that could be at play include a direct blood pressure-lowering effect of the GLP-1, potentiation of certain antihypertensive medications by GLP-1s, dehydration, decreased sympathetic nervous system activity and blood vessel relaxation."
Clinical Implications and Medication Adjustments
Medication was changed — either by dose reduction or by cutting the number of therapies — in approximately 25% of patients during the study period, according to the researchers. Eimer emphasized that these findings should not deter appropriate use of GLP-1s, which he described as "incredibly effective at helping patients lose weight."
"I'm a big proponent of GLP-1s, they are huge," Eimer said. "I'm just saying, let's watch out for hypotensive events in select patients because I think there's the potential to do harm."
He stressed that "blood pressure needs to be monitored in patients who are taking GLP-1s at the initiation of therapy and during dose escalation. Patients should also be warned about signs of low blood pressure so that they can report them."
Concerns About Unsupervised Access
Eimer expressed particular concern about patients obtaining GLP-1s without direct clinical oversight. "A lot of patients are getting these drugs not from treating physicians necessarily. If I'm a patient, and I go to an online prescriber and they start sending me this drug, they're not checking my blood pressure. They're not asking me if I'm lightheaded or dizzy," he said.
The study is titled, "GLP1 Receptor Agonists and the Risk of Significant Hypotension (搜索) Among Patients with Metabolic Cardiovascular Renal Disease: Too Much of A Good Thing?" Eimer noted that "larger studies are needed to better define who is at risk and to look at things like types of blood pressure medication, amount and pace of weight loss, etc."