Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the treatment of type 2 diabetes (T2D) and obesity, offering substantial benefits for glycemic control, weight reduction and cardiometabolic health.
But as more patients use these medications, clinicians are also learning more about how rapid or considerable weight loss may affect areas beyond the waistline.
As such: A new recent retrospective cohort study published in Ophthalmic Plastic & Reconstructive Surgery suggests those effects may extend to the tissues around the eyes, particularly for those patients treated for obesity.
First, let’s take a step back and look at GLP-1RAs.
For a rundown on what this class of medications do—plus how they work and FDA-approved examples—click here. (Also check out all of our prior coverage on them).
Most notably: GLP-1RAs mimic the effects of the naturally occurring GLP-1 hormone, with a few key properties making them effective treatments for T2D and obesity.
- Promoting glucose-dependent insulin secretion
- Reducing glucagon release
- Delaying gastric emptying
- Decrease food intake
Tie this into the periorbital region.
The growing use of GLP-1RAs has also brought attention to facial volume loss sometimes informally described as “Ozempic face.”
To note: Though not a formal medical diagnosis—nor necessarily unique to one medication— this describes changes such as facial hollowing, skin laxity and a more aged appearance that may accompany substantial weight loss.
So because the periorbital region contains delicate skin and relies on underlying fat and soft tissue for structural support, volume loss could theoretically contribute to changes around the eyelids and brows.
So, what did the researchers set out to study?
They wanted to determine whether GLP-1RA use was associated with clinically documented periorbital changes among patients with either T2D or obesity.
Their method: utilizing electronic health record (EHR) data from the TriNetX Research Network to conduct a retrospective cohort study.
Rather than combining all participants into one analysis, the researchers created separate cohorts for patients treated for T2D and those treated for obesity.
The following diagnoses were tracked:
- Brow ptosis
- Blepharoptosis
- Dermatochalasis
- Ectropion
- Entropion
Subsequent interventions of brow ptosis repair, blepharoptosis repair, blepharoplasty, rhytidectomy and botulinum toxin A treatment were also observed.
And who was included?
The diabetes analysis compared T2D patients who used a GLP-1RA with GLP-1RA-naive patients treated with insulin or other antidiabetic medications.
- After matching, each diabetes group included 334,288 patients (mean age: 60.7).
- Approximately 60.8% were white, 16.8% were Black and 6.5% were Asian.
The obesity analysis compared GLP-1RA users with patients who had obesity—defined as a body mass index of at least 30 kg/m²—but did not have T2D, had not undergone bariatric surgery and had not previously used a GLP-1RA.
- After matching, each obesity group included 270,923 patients (mean age of 48.2).
- Approximately 65.8% were white, 16.2% were Black, 1.5% were Asian and 30% were Hispanic or Latino.
And what did they find?
Among patients with T2D, use of any GLP-1RA was associated with a significantly higher likelihood of developing brow ptosis compared with matched controls.
GLP-1RA users in the diabetes cohort were also more likely to receive botulinum toxin A, although the study could not determine the precise clinical or cosmetic indication for every treatment.
The differences were more extensive in the obesity cohort. Compared with GLP-1RA-naive controls, patients with obesity who used a GLP-1RA were significantly more likely to develop:
- Brow ptosis
- Dermatochalasis
They were also more likely to undergo:
- Brow ptosis repair
- Blepharoptosis repair
- Blepharoplasty
- Rhytidectomy
- Botulinum toxin A treatment
The researchers did not identify significantly higher rates of every outcome studied. Instead, the pattern was concentrated around brow descent, excess eyelid skin and procedures intended to address facial or periorbital changes.
Why were the findings stronger in patients treated for obesity?
The authors suggested that patients with obesity may begin treatment with more facial and periorbital adipose tissue and may experience more substantial weight loss than patients using GLP-1RAs primarily to manage diabetes.
As that tissue volume decreases, the skin and muscles around the brow and eyelids may lose some of their underlying support. This could make brow ptosis, dermatochalasis or other contour changes more noticeable.
Go on …
The interpretation is consistent with emerging research on GLP-1RA-associated facial volume loss.
However, the current study did not include patients’ actual weight-loss totals, pretreatment photographs or direct measurements of periorbital fat.
- As a result, it cannot confirm that fat loss was the mechanism responsible for the observed associations.
It was also important to distinguish between changes caused directly by a medication and those associated with the weight loss the medication produces.
The study identified a relationship between GLP-1RA exposure and documented outcomes, but it could not fully separate those possibilities.
Any limitations we keep in mind?
First, the study was retrospective and relied on diagnostic and procedural coding within electronic health records. Coding may vary among clinicians and healthcare organizations, and the database could not confirm every diagnosis through photographs or standardized oculoplastic examinations.
The researchers also could not evaluate:
- The exact GLP-1RA used by every patient in relation to each outcome
- Medication dose
- Duration of treatment
- Treatment adherence
- Rate or amount of weight loss
- Baseline facial anatomy
- Skin elasticity or age-related facial changes
- Whether procedures were medically necessary or primarily cosmetic
The diabetes and obesity cohorts also had different follow-up windows because GLP-1RAs were approved for those indications at different times. Outcomes were assessed over as many as 20 years for the diabetes cohort but only three years for the obesity cohort.
Finally, an association does not prove that GLP-1RAs directly caused the changes or procedures.
So, how did the authors interpret the findings?
They concluded that GLP-1RA use among patients with T2D or obesity was associated with significant periorbital changes and subsequent interventions.
They believed the more pronounced findings among patients treated for obesity were likely related to greater adipose tissue accumulation before treatment followed by more noticeable tissue loss.
At the same time, the results should be viewed as an early population-level signal rather than proof of a direct pharmacologic effect. Prospective studies that include standardized facial imaging, weight-change data, medication exposure and periorbital measurements will be needed to clarify the relationship.
And what should ECPs take away from this?
The findings provide useful context for eye care professionals (ECPs).
Patients experiencing rapid weight loss may mention eyelid heaviness, increased upper-eyelid skin, brow descent or dissatisfaction with changes in facial appearance.
- Some may ultimately seek evaluation from an oculoplastic surgeon or another qualified specialist.
It may also be helpful to document whether symptoms are functional or cosmetic.
- Brow ptosis and dermatochalasis can affect appearance, but in sufficiently advanced cases, they may also contribute to superior visual field obstruction or difficulty keeping the eyes comfortably open.
And lastly?
This study also adds another consideration to the expanding ophthalmic conversation surrounding GLP-1RAs.
Previous research has examined potential associations with diabetic retinopathy, diabetic macular edema, glaucoma and ischemic optic neuropathy.
The current findings focus on a different area: structural and soft-tissue changes around the eyes.