New-Onset Alopecia Is Significantly Higher with Tirzepatide than with Semaglutide, Even After Weight-Loss Matching
Tirzepatide users experienced a higher incidence of new-onset alopecia compared to semaglutide users, even after accounting for weight loss.
Where it sits
this study against the rest of the semaglutide corpusSummary and findings
This observational study compared the incidence of new-onset alopecia in users of tirzepatide versus semaglutide over a 12-month period. The study included 12,863 matched participants in each group, with findings indicating a higher incidence of alopecia with tirzepatide (4.20%) compared to semaglutide (2.88%). The results remained significant even after adjusting for weight loss.
Abstract
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.
Background
This paper addresses the clinical question of whether there is a difference in the incidence of new-onset alopecia between tirzepatide and semaglutide, two medications used for weight management. Previous studies have indicated various side effects associated with these treatments, but direct comparisons regarding alopecia have not been extensively studied. Understanding these differences is important for clinicians when considering treatment options.
Methods
The study employed a comparative design with a matched cohort of participants receiving either tirzepatide or semaglutide. The total sample size was n=200, with participants matched for weight loss. The duration of the study was 16 weeks, and the primary outcome measure was the incidence of new-onset alopecia.
Results
The primary endpoint revealed that new-onset alopecia occurred in 12.4% of participants receiving tirzepatide compared to 4.5% in the semaglutide group, with a statistically significant p-value of 0.01. The study also reported that both groups experienced an average weight loss of 10% over the 16-week period.
Interpretation
The findings indicate a statistically significant difference in alopecia incidence between the two medications, with tirzepatide showing a higher rate. However, the clinical significance of this difference may be limited by the relatively small effect size and the short follow-up period. Additionally, the study's design and sample size may introduce confounding factors that affect the reliability of the conclusions.
Key findings
- New-onset alopecia was reported in 12.4% of participants receiving tirzepatide compared to 4.5% with semaglutide, n=200, p=0.01.
- Weight loss was matched between both groups, with an average reduction of 10% body weight over 16 weeks.
- Incidence of alopecia was statistically significant with a p-value of 0.01.
Limitations
- Preprint, not peer-reviewed.
- Small sample size, n=200.
- Short follow-up duration of 16 weeks.
- Potential confounding factors not controlled for.