New-Onset Alopecia Is Significantly Higher with Tirzepatide than with Semaglutide, Even After Weight-Loss Matching

Alopecia is an emerging concern during tirzepatide or semaglutide therapy for weight management, but whether it is a consequence of weight loss or reflects incretin-specific biology remains unclear. Here we conduct an observational study comparing new users of tirzepatide (Zepbound, Mounjaro) or semaglutide (Wegovy, Ozempic, Rybelsus) with at least two prescriptions, no documented alopecia prior to the first prescription, and complete 12-month follow-up. Incident alopecia was defined using harmonized diagnosis codes and AI-curated clinical notes. Propensity-score matching was performed to balance tirzepatide and semaglutide users on age, race, sex, baseline BMI, and type 2 diabetes. In the matched cohorts (n=12,863 per arm), incident alopecia was more frequent with tirzepatide than with semaglutide (4.20% vs 2.88%; risk ratio [RR]: 1.46; 95% CI [1.28-1.66]; P<0.001). After additional matching on achieved weight loss (n=11,046 per arm), incident alopecia remained significantly higher after tirzepatide than semaglutide (4.24% versus 3.33%; RR: 1.27 [1.11-1.45]; P<0.001). By 6 months, incident alopecia had occurred in 1.55% of tirzepatide users versus 1.24% of semaglutide users, widening by 12 months to 4.20% versus 2.88%, respectively (hazard ratio [HR]: 1.46 [1.28-1.67]; log-rank P<0.001). Incident alopecia remained significantly more frequent with tirzepatide than semaglutide across clinically relevant strata (all P<0.001), including among patients with 20-to-30% weight loss, a range highlighted in pivotal obesity trials (RR: 1.44); in the low and high maximum-dose strata (RR: 1.76 and 1.39, respectively); and among patients with 4-6 prescriptions, a proxy for longer treatment duration (RR: 1.65). Analysis of newly initiated hair-loss therapies showed significantly higher minoxidil (Rogaine) initiation after tirzepatide than after semaglutide (RR, 2.04; P=0.002). Among 8,985 female patients, incident alopecia occurred in 5.44% of tirzepatide users versus 3.63% of semaglutide users (RR: 1.50 [1.31-1.72]; P<0.001), with significant differences in the 10-to-20% weight-loss band (RR: 1.41 [1.11-1.78]; P=0.004) and in the 20-to-30% weight-loss band (RR, 1.47; 95% CI, 1.06 to 2.04; P=0.018). Among tirzepatide users, incident-alopecia developers were more often female than non-developers (90.6% vs 68.9%, SMD: +0.56), and were enriched for underlying endocrine conditions including menstrual irregularity (20.0% vs 13.9%, SMD: +0.17), hypothyroidism (28.1% vs 21.6%, SMD: +0.15), and polycystic ovarian syndrome (6.7% vs 3.6%, SMD: +0.14). Repeated measurements of ferritin, iron, vitamin B12, folate, vitamin D, and zinc showed no significant nutrient decline accompanying incident alopecia. Exploratory single-cell RNA-seq analyses showed no GLP1R or GIPR expression in scalp follicular keratinocytes and identified multiple dermato-immune cell types that expressed GIPR but not GLP1R. Overall, in routine care, incident alopecia was higher after initiation of tirzepatide than semaglutide, motivating prospective comparative studies of incretin-based therapies.