GLP-1s Tied to Detached Fingernails in New Study

Users of GLP-1 receptor agonists had as much as fourfold higher likelihood for nail disorders, particularly onycholysis (separation of the fingernails or toenails), compared with patients not taking the drugs, a large prospective study showed.

The data showed that 39.3% of 575 GLP-1 agonist users had onycholysis as compared with 8.7% of obese/diabetic patients not taking the drugs, which translated into a 4.5-fold higher likelihood. For dyschromia (nail discoloration), the rates were 45.6% versus 17.0%, representing a 2.7-fold greater likelihood among GLP-1 receptor agonist users. Nail fragility and presence of ridges or grooves also were more common in GLP-1 agonist users.

Overall, 66.3% of GLP-1 drug users and 52.8% of non-users reported any type of nail disorder, a statistically significant difference (P<0.001). An analysis that took into account comorbidities, including dermatologic conditions, still showed almost a two- to threefold higher likelihood of onycholysis and dyschromia among GLP-1 agonist users. An analysis limited to patients who lost weight did not appreciably change the results, reported Bianca Maria Piraccini, MD, PhD, of the University of Bologna in Italy, at the European Academy of Dermatology and Venereology (EADV) meeting in Vienna.

Almost half of patients taking GLP-1 receptor agonists had a history of nail problems before starting the drugs, said Piraccini. Sensitivity analyses accounting for that continued to show a two- to four-fold difference in onycholysis and dyschromia among GLP-1 agonist users. However, an analysis of new-onset nail lesions showed no difference in onycholysis or dyschromia between GLP-1 drug users and non-users. Investigators think the true association probably lies somewhere between the fully adjusted and new-onset results, leaving room for possible effects attributable to the drugs.

“After adjusting for age, sex, country, comorbidities and so on, we have a really high prevalence of onycholysis in patients undergoing GLP-1 receptor agonist treatment,” said Piraccini. “This is quite unusual because onycholysis cannot be related to weight loss. Weight loss is commonly associated with nail plate surface abnormalities, which can be described as rough, uneven nails. Nail detachment is not a sign of low caloric intake or protein deficiency or other signs, so we think it could be directly related to the drug. This will prompt us to do more studies.”

For clinicians who have patients on GLP-1 receptor agonists, the message is “don’t forget to look at the nails and ask if [nail abnormalities] were present prior to starting the treatment or if the onset was during treatment,” she added. “Look carefully at [affected nails] and try to correlate them to the drug. I think that a specific drug effect is possible and warrants confirmation.”

In response to a question, Piraccini said investigators ruled out other possible causes of onycholysis, such as trauma or fungal infection, because patients did not have active nail disorders when they started treatment with a GLP-1 agonist.

Co-investigator Charles Taieb, MD, PhD, of European Market Maintenance Assessment in Fontenay-sous-Bois, France, said the study is one of the first large-scale analyses of nail and hair effects of GLP-1 receptor agonists.

“Until now, nail changes associated with GLP-1 therapies had essentially been anecdotal,” Taieb said in an EADV press release. “Our findings show a clear association, but they also underline an important point: Not everything that happens during GLP-1 treatment is necessarily caused by the treatment itself.”

Interesting Observation, But …

Though the study raises an interesting issue, the results should be viewed cautiously, said Joe Tung, MD, of the University of Pittsburgh Medical Center, who was not involved in the study.

“It should not worry people who are currently doing well on a GLP-1 medication, and I would be cautious about reading it as proof that the drugs themselves have any direct effects on nails,” Tung told MedPage Today. “At first glance, nail lifting looked about four times more common in GLP-1 users … . However, that gap shrank considerably once the researchers accounted for other comorbid health conditions and nutritional deficiencies.”

“In the most rigorous analysis presented, which counted only nail changes that began after starting the GLP-1 medications, the association disappeared entirely … . That happened in part because about half of GLP-1 users said their nail problems were already present before treatment. The results were also self-reported in an online survey without a dermatologist examining anyone’s nails.”

The findings have biologic plausibility, as rapid weight loss and lower intake of protein and micronutrients could affect the rapidly growing nail unit, just as it can trigger hair shedding, Tung added.

“I would encourage patients who notice nail changes to see a dermatologist, because common causes of nail disorders are very treatable,” he said. “These findings alone, however, would not justify stopping an otherwise beneficial GLP-1 medication for the appropriate patient.”

Study Details, Key Findings

The study involved patients recruited in France, the United States, Brazil, and Mexico. The 575 GLP-1 receptor agonist users were compared with a control group of 1,329 participants with obesity and/or type 2 diabetes who had never used a GLP-1 drug. Patients in the control group were older (56.7 vs 45.3 years), but sex distribution was approximately 50/50 in both groups.

An unadjusted analysis showed a 4.5-fold higher prevalence of onycholysis and 2.7-fold higher prevalence of dyschromia. A series of adjusted analyses produced the following odds ratios for onycholysis and nail dyschromia, respectively:

• Age, sex, country: adjusted OR (aOR) 4.4 (95% CI 3.3-5.8) and aOR 3.3 (95% CI 2.6-4.2)
• Adding comorbidities and nutritional deficiencies: aOR 2.9 (95% CI 2.2-3.9) and aOR 2.2 (95% CI 1.7-2.8)
• Sensitivity, new-onset only: aOR 1.0 (95% CI 0.6-1.7) and aOR 0.9 (95% CI 0.6-1.3)

Analyses limited to patients who lost weight showed similar results for the prevalence of onycholysis and dyschromia, which Piraccini reported as odds ratio ranges:

• Age, sex, country: aOR 4.4/3.3
• Adding comorbidities and nutritional deficiencies: aOR 2.9/2.2
• Sensitivity, new-onset only: aOR 1.0/0.9

Piraccini said the results provide a basis for additional studies examining the nail effects of GLP-1 drugs.