Risk of hair loss associated with glucagon-like peptide-1 receptor agonists in adults with type 2 diabetes: target trial emulation

Abstract Objective To examine the association between glucagon-like peptide-1 (GLP-1) receptor agonists and the risk of incident alopecia (hair loss) in adults with type 2 diabetes, compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Design Target trial emulation. Setting Electronic health records from Penn Medicine. Participants Adults (>18 years) with type 2 diabetes. Exposures New initiation of GLP-1 receptor agonists, SGLT-2 inhibitors, or DPP-4 inhibitors between January 2019 and September 2024. Main outcome measures Outcomes of interest included incident alopecia and its subtypes, identified by using diagnostic codes. Stabilised inverse probability of treatment weighting was applied to balance baseline covariates between treatment groups, and Cox proportional hazards models were used to estimate hazard ratios with 95% confidence intervals. Multiple sensitivity (including negative control outcome calibration) and subgroup analyses were done to assess robustness. Results This study included 12 004 GLP-1 receptor agonist initiators and 15 221 SGLT-2 inhibitor initiators in the GLP-1 receptor agonist versus SGLT-2 inhibitor comparison and 11 964 GLP-1 receptor agonist initiators and 11 238 DPP-4 inhibitor initiators in the GLP-1 receptor agonist versus DPP-4 inhibitor comparison. After stabilised inverse probability of treatment weighting adjustment, use of GLP-1 receptor agonists was associated with a higher risk of alopecia than use of SGLT-2 inhibitors (hazard ratio 1.37, 95% confidence interval 1.08 to 1.73) or DPP-4 inhibitors (1.68, 1.28 to 2.20). The associations were consistent across sensitivity and subgroup analyses, with attenuation after negative control outcome calibration. Subtype analyses indicated that the association was specific to non-scarring alopecia, with hazard ratios of 1.53 (1.18 to 1.97) and 1.72 (1.28 to 2.31) compared with SGLT-2 inhibitors and DPP-4 inhibitors, respectively. Conclusions Use of GLP-1 receptor agonists was associated with an increased risk of non-scarring alopecia in adults with type 2 diabetes. Although the absolute risk is low, awareness of this potential effect may help to inform treatment decisions.