GLP-1s linked to up to 68% higher hair loss risk in T2DM patients

The use of glucagon-like peptide-1 (GLP-1) receptor agonists to treat type 2 diabetes and obesity is associated with an increased risk of hair loss (alopecia) in adults with type 2 diabetes, a study published by The British Medical Journal (BMJ) has reported. Although the absolute risk is low, awareness of this potential effect may help inform shared treatment decisions, according to the study’s researchers from the University of Pennsylvania, Philadelphia, PA.

Alopecia 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.

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 vs. 65), had a higher body mass index (36.2 vs. 32.3), and had lower rates of cardiovascular and chronic kidney diseases. Similarly, GLP-1 users were younger (mean age 58 vs. 67) and had a higher body mass index (36.2 vs. 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 vs. 5.04 per 1,000 person-years) and a 68% higher risk than use of DPP-4 inhibitors (6.53 vs. 3.89 per 1,000 person-years).

Further analyses indicated that the association was specific to nonscarring 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 note, 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 the 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 say 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 conclude, "Our findings extend previous anecdotal safety signals and provide more systematic evidence to inform clinical awareness of this potential adverse effect."

The findings were reported in the paper, ‘Risk of hair loss associated with glucagon-like peptide-1 receptor agonists in adults with type 2 diabetes: target trial emulation’, published in The BMJ. To access this paper, please click here