New research links GLP-1 medications such as semaglutide and tirzepatide to a doubled risk of potentially blinding eye diseases.
The most commonly used types of GLP-1 receptor agonists are semaglutide
and tirzepatide, which are used to treat type 2 diabetes and aid weight loss.
- Past studies have linked GLP-1 medications to a risk of potentially
blinding eye diseases.
- A new study reports that older adults with diabetes taking any type
of GLP-1 medication may be at a heightened risk for developing neovascular
age-related macular degeneration (nAMD).
Recent
tracking polls report that about one in eight people have
taken a glucagon-like peptide-1 receptor agonist, more
commonly known as GLP-1 medications.
Originally
used to help treat type 2
diabetes, these medications have gained in popularity over the last
few years for weight loss.
Currently,
the most common types of GLP-1 drugs are semaglutide — sold under the brand names Ozempic for
type 2 diabetes and Wegovy for
weight loss — and
Just like
any medication, GLP-1 drugs have possible side effects and complications. One
potential complication was first reported in July 2024 when a study found
people using semaglutide were at a
Now, a new
study recently published in the journal
For this study,
researchers analyzed health records from 2020 to 2023 of more than 139,000
Ontario residents with an average age of 66 and diagnosis of diabetes.
Participants who used GLP-1 medications did so for more than six months.
“Our study
included any GLP-1 receptor agonists that were prescribed during the study
period in Ontario, Canada; we did not exclude any specific type of these
medications,” Rajeev H. Muni, MD MSc FRCSC, associate
professor and vice chair of Clinical Research in the Department of
Ophthalmology and Vision Sciences at the University of Toronto in Canada, and
principal investigator of this study explained to Medical News Today. “However, semaglutide
represented the vast majority of use in our cohort, accounting for 97.5% of all
GLP-1 prescriptions.”
“
“Furthermore,
while Wegovy was approved in late 2021, our study focused on patients with
diabetes from 2020 to 2023,” he added. “Therefore, it is very likely that the
semaglutide included in our analysis was prescribed as Ozempic, which is
indicated for blood sugar control in type 2 diabetes.”
Older adults
taking GLP-1s at 2-fold higher risk
Upon analysis,
researchers found that participants with diabetes taking a GLP-1 medication had
a two-fold higher risk of developing nAMD — a type of AMD where
malformed blood vessels grow underneath the retina, causing fluids to leak into the macula of the eye.
There is
currently no cure for nAMD and it is a condition that can potentially cause
blindness.
“We found
that among patients with diabetes aged 66 and older, the incidence of nAMD was
approximately 1 in 1,000 in those who had never used GLP-1 receptor agonists,
compared to about 2 in 1,000 among those who had been exposed to these
medications for at least six months,” Muni said. “While the absolute risk
remains low, this represents a relative doubling in risk.”
“While our
findings should not prompt alarm, they do warrant increased clinical
awareness,” he continued. “These medications have well-established benefits for cardiovascular,
Eye
disease risk higher in those using GLP-1s for longer
Additionally,
Muni and his team observed that the highest nAMD risk was associated with participants
who had used GLP-1 medications for the longest amount of time.
“We
observed a clear dose-response relationship in our analysis, with the risk of
nAMD increasing as the duration of GLP-1 receptor agonist exposure increased,”
Muni explained. “This finding is clinically meaningful because it suggests that
the risk may accumulate over time.”
“Given
that many individuals use these medications chronically, whether for blood sugar
control or for weight loss, the long-term ocular safety of
GLP-1 RAs requires further investigation,” he continued. “While observational
data can’t prove causation on its own, seeing a graded relationship like this
suggests that prolonged exposure could play a role in increasing risk; however,
this needs to be validated in future studies.”
The study’s limitations
MNT also talked to Demetrios Vavvas, MD, PhD,
director of the retina service at Mass Eye and Ear in Massachusetts, about this
research.
Vavvas
commented that the study’s strength is on its massive scale of real-world data,
the robust statistical technique used, and the evidence it found of a
“dose-response” relationship.
“The risk
of developing nAMD appeared to increase the longer a patient was exposed to the
medication,” he continued. “This type of pattern makes a potential link more
compelling than a single, static finding and provides a significant signal that
warrants serious follow-up investigation.”
However,
Vavvas did point out that the study has some limitations.
“The most
significant limitation is that this study can only show an association, not
prove that the drug causes this eye condition. This is because critical risk
factors like smoking, obesity (BMI), and sun exposure
were not accounted for in the data. Since GLP-1 RAs are often prescribed to
patients with obesity, this single unmeasured factor could be the true driver
of the observed risk.”
— Demetrios Vavvas, MD, PhD
“Second,
the results may be influenced by surveillance bias,” Vavvas continued.
“Patients starting a powerful new medication like a GLP-1 RA are likely to be
monitored more closely by their doctors. This increased medical attention could
lead to a higher likelihood of their eye problems being detected and treated, which
is what the study measured, creating the appearance of increased risk.”
“Thirdly,
the actual events were very small — less than 0.2% so despite statistical
adjustment results may not be accurate,” he added. “Lastly as the majority of
GLP-1 RAs in this study were semaglutide, this may not apply to all GLP-1 RAs
and additionally, because the analysis excluded over 26,000 patients who could
not be matched, the results may not apply to the full spectrum of patients
taking these drugs in the real world, particularly those with more complex
health profiles.”
Monitoring
eye health important on GLP-1 drugs
MNT spoke with David I. Geffen, OD, FAAO, director of
optometric and refractive services at the Gordon Schanzlin New Vision in La
Jolla, CA, about this study.
Geffen
commented that as GLP-1 medications are being prescribed to a huge number of
patients — and as it’s been observed that not all patients are symptom free and
not side effect free — doctors must be very careful to make sure their
patients’ eye health is not compromised utilizing these medications.
“It is
important to make sure that we know our patients are taking these medications,”
he explained. “This study shows that as new medications are approved we need to
be careful as long term side-effects may be seen that we were not aware of.”
“Diabetes
is very common in our practices and many of our patients are put on the
GPL-1s,” Geffen continued. “We need (to) be vigilant in examining patients with
diabetes. If using these meds, it is even more important. One study is not
enough to make too many assumptions however in deciding to use these meds. The
GLP-1 medications have shown many benefits for most patients.”
“It is
important to carry on further studies in other countries to see if this is seen
in other populations,” he added. “It would be important to know more of the
demographics of the afflicted populations. Knowing the status of the retina in
the individuals before being put on the medications would be helpful in
determining safety profiles.”
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