In what seems like a trade-off between weight loss and hair loss, a new study has found that the glucagon-like peptide-1 (GLP-1) receptor agonists — commonly called weight-loss drugs — used to treat type 2 diabetes and obesity is associated with an increased risk of hair loss (alopecia) in adults.
Although the absolute risk is low, awareness of this potential effect may help inform shared treatment decisions, said the researchers in the paper titled “Risk of hair loss associated with glucagon-like peptide-1 receptor agonists in adults with type 2 diabetes: Target trial emulation”, which was published in the British Medical Journal (BMJ) on Wednesday.
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Alopecia is the medical term for hair loss. It has been reported as a possible side effect of GLP-1 receptor agonists, particularly semaglutide and tirzepatide. However, studies assessing the risk of alopecia associated with GLP-1 receptor agonists compared with other diabetes drugs are lacking, they said.
“(GLP-1) receptor agonists are increasingly prescribed for the management of type 2 diabetes and, more recently, for obesity treatment in populations without diabetes. Recent postmarketing reports have suggested a possible association between GLP-1 receptor agonist use and alopecia (hair loss),” read the paper.
“Given the expanding clinical use of GLP-1 receptor agonists, particularly in younger and non-diabetic populations, timely evidence is needed to inform clinical practice and regulatory decisions,” said the authors.
To address this, researchers used electronic patient data from the University of Pennsylvania Health System (Penn Medicine) to compare rates of alopecia in adults with type 2 diabetes who started using GLP-1 receptor agonists or other types of diabetes drugs known as SGLT-2 inhibitors, or DPP-4 inhibitors.
In total, 12,004 patients using GLP-1 receptor agonists were compared with 15,221 using SGLT-2 inhibitors and a further 11,964 GLP-1 users were compared with 11,233 DPP-4 inhibitor users between January 2019 and September 2024.
Compared with SGLT-2 inhibitor users, GLP-1 receptor agonist users were younger (mean age 58 v 65), had a higher body mass index (36.2 v 32.3), and lower rates of cardiovascular and chronic kidney diseases. Similarly, GLP-1 users were younger (mean age 58 v 67) and had a higher body mass index (36.2 v 31.3) than DPP-4 inhibitor users.
After adjusting for potentially influential factors including age, sex, ethnicity, pre-existing conditions, other medication use, and body mass index, use of GLP-1 receptor agonists was associated with a 37% higher risk of alopecia than use of SGLT-2 inhibitors (6.91 v 5.04 per 1,000 person years) and a 68% higher risk than use of DPP-4 inhibitors (6.53 v 3.89 per 1,000 person years).
Further analyses indicated that the association was specific to non-scarring alopecia (where hair follicles remain intact, leaving the potential for regrowth) with an increased risk of 53% and 72% compared with SGLT-2 inhibitors and DPP-4 inhibitors, respectively.
The authors point out that rapid weight loss is a well-established trigger of hair shedding and can also lead to iron or zinc deficiencies, which disrupt the hair growth cycle. Hormonal changes may also be relevant, they said, although further studies are needed to clarify the underlying mechanisms.
They also acknowledge several study limitations. For example, a lack of clinical information limited their ability to assess details such as severity, extent, duration and reversibility of alopecia after stopping treatment. Nor can they rule out the possibility that other unmeasured factors may have influenced their results.
However, they said, this was a rigorous study based on high-quality data from a large representative cohort and results were consistent after additional analyses, suggesting they are reliable.
As such, they said, “Our findings extend previous anecdotal safety signals and provide more systematic evidence to inform clinical awareness of this potential adverse effect.”
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