Abstract
Introduction
Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrate remarkable efficacy for weight management, emerging pharmacovigilance data suggest an increased hair loss risk, particularly with newer agents. This study investigated the prevalence, risk factors, and clinical impact of hair shedding in GLP-1 RA users in Saudi Arabia.
Methods
A cross-sectional survey was conducted between September 2024 and January 2025 of current and former GLP-1 RA users. Participants with preexisting hair loss were excluded from the study. Hair shedding prevalence, associated factors, and the impact on treatment discontinuation were assessed using validated questionnaires. Multivariate logistic regression was used to identify independent predictors.
Results
Among 152 eligible participants (87.5% female, median body mass index 32.1 kg/m2), 70.4% (n = 107) reported hair shedding after GLP-1 RA initiation, which was markedly higher than the 3–7% reported in clinical trials. Tirzepatide users had the highest prevalence (76.7%), followed by semaglutide (64%) and liraglutide (54.5%). Hair shedding was significantly associated with female sex (92.5% vs. 75.6% in males, p = 0.009), greater magnitude of weight loss (82.7% prevalence with ≥15% weight loss vs. 40% with <5%, p = 0.002), and medication discontinuation (63.6% vs. 40% in non-shedders, p = 0.013). Multivariable analysis confirmed independent associations with increasing weight loss (OR 1.79, 95% CI: 1.19–2.76, p = 0.006) and female sex (OR 3.57, 95% CI: 1.20–11.11, p = 0.023). Critically, 39.7% of the affected patients cited hair shedding as their reason for discontinuation, although 37.7% reported resolution after stopping treatment. The median weight loss was 15.9% [IQR 8.69–22.5], with 53.3% achieving ≥15% reduction.
Conclusion
Hair shedding affects seven out of ten GLP-1 RA users in real-world settings, representing a ten-fold higher prevalence than that reported in registration trials. This under-recognized phenomenon during GLP-1 RA therapy significantly affects treatment adherence, particularly among women who achieve substantial weight loss. Proactive counseling and nutritional optimization strategies are essential to maintain treatment persistence.
Keywords: GLP-1 receptor agonists, Hair loss, Telogen effluvium, Weight loss, Drug safety
Introduction
Obesity is a global health challenge, with a steadily rising prevalence across diverse populations. According to the largest pooled analysis of 3,663 studies including 222 million participants, the global prevalence of obesity has more than doubled since 1990, with the highest burdens in the Middle East, North Africa, Polynesia, and the Caribbean [1]. It is strongly associated with an increased risk of cardiovascular disease, type 2 diabetes mellitus, hypertension, certain cancers, and impaired quality of life [2]. Individuals with obesity face up to a four-fold higher risk of diabetes and a two-fold higher risk of premature death [3]. As of 2025, approximately 5 million adult noncommunicable disease deaths annually, primarily from diabetes, stroke, heart disease, and cancer, are attributable to a high body mass index (BMI, ≥25 kg/m2) [4].
While lifestyle interventions remain the cornerstone of weight management, their long-term efficacy is limited, with many individuals regaining a significant portion of lost weight within 6–12 months after the intervention ends, and sustained weight loss beyond 5 years remains rare [5, 6]. This has driven the development of pharmacological agents that target appetite and metabolic processes. Among these, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as one of the most effective therapies for weight reduction [7].
Originally introduced for the treatment of type 2 diabetes mellitus, GLP-1 RAs mimic endogenous GLP-1 to enhance insulin secretion, delay gastric emptying, and suppress appetite [8]. More recently, high-dose formulations of liraglutide, semaglutide, and the dual GIP/GLP-1 agonist tirzepatide have demonstrated substantial weight loss in clinical trials, with reductions ranging from 10% to over 20% of the baseline body weight [7, 9]. These outcomes are comparable to those observed with bariatric surgery and have positioned GLP-1 RAs as frontline therapies for pharmacological obesity management [10].
Despite their efficacy, concerns regarding the safety profile of GLP-1 RAs continue to emerge. Gastrointestinal side effects such as nausea, vomiting, and diarrhea are the most common and well-documented adverse events [11]. However, newer reports have identified fewer conventional adverse effects, including dermatological manifestations [12]. In a recent disproportionality analysis using data from the FDA Adverse Event Reporting System (FAERS), semaglutide was associated with a 2.5-fold increase in reporting odds for alopecia, whereas tirzepatide showed a 1.7-fold increase compared to background levels of reporting [13]. A recent retrospective cohort study analyzing US health claims data found that semaglutide use was associated with a 2.08-fold increased risk of hair loss in women compared to bupropion-naltrexone, highlighting a potential sex-specific adverse effect that warrants further investigation [14].
The mechanisms linking GLP-1 RAs to hair shedding are not yet fully understood. One hypothesis is that the rapid weight loss induced by these agents may precipitate telogen effluvium (TE), a transient, non-scarring alopecia characterized by diffuse hair shedding following metabolic or physiological stress [15]. TE has been well documented in patients undergoing bariatric surgery, where a systematic review and meta-analysis found that 57% of patients (95% confidence interval [CI]: 42–71%) experienced hair loss after metabolic and bariatric surgery, typically occurring within the first 3–6 months postoperatively [16]. This suggests that the hair loss observed with GLP-1 RAs may be secondary to rapid metabolic shifts, rather than a direct drug effect.
The clinical implications of hair shedding in patients treated with GLP-1 RAs are significant. While TE is usually reversible, hair loss can cause psychological distress and contribute to treatment discontinuation, potentially limiting the long-term success of weight management [17]. In a large US cohort study, new gastrointestinal diagnoses, used as a proxy for adverse effects, were significantly associated with higher odds of GLP-1 RA discontinuation at 12 months (odds ratio [OR] 1.04, 95% CI: 1.02–1.06), suggesting that tolerability issues play a meaningful role in long-term adherence [18]. In addition, a recent review emphasized that drug-induced alopecia associated with semaglutide and tirzepatide, although not widely reported in clinical trials, has emerged as a potential adverse event in pharmacovigilance databases [13].
Given the expanding use of GLP-1 RAs for obesity and emerging concerns regarding hair shedding, there is a pressing need to investigate this adverse event in non-trial populations. The present study examined the prevalence of hair shedding among GLP-1 RA users in Saudi Arabia, explored associated risk factors such as the degree of weight loss and treatment duration, and assessed whether hair loss influences medication discontinuation.
Methods
Study Design and Setting
A cross-sectional survey was conducted between September 2024 and January 2025 to examine the association between GLP-1 receptor agonist use and hair shedding in weight loss medication users in Saudi Arabia. The study protocol was approved by the Institutional Review Board of Qassim University, and all participants provided informed consent prior to participation.
Study Population
Participants were eligible for inclusion if they (1) were aged 18 years or older; (2) were current or former users of GLP-1 receptor agonists for weight loss (semaglutide, tirzepatide, liraglutide, or dulaglutide); (3) were residents of Saudi Arabia; and (4) provided complete responses. Participants were excluded if they (1) had never used weight loss medications, (2) were nonresidents of Saudi Arabia, (3) reported hair loss before initiating weight loss treatment, (4) provided incomplete questionnaire responses for primary variables, or (5) had duplicate or invalid survey entries identified during data validation.
Sample Size Calculation
The minimum sample size was calculated using Cochran’s formula with a 95% CI, assumed prevalence of 50%, and a margin of error of 5%, yielding a target of 385 participants. Participants were recruited using convenience sampling through online platforms and social media.
Data Collection Procedures
A structured, self-administered questionnaire was developed specifically for this study to capture demographic characteristics, medication history, anthropometric data, and adverse events including hair shedding. The instrument underwent content validation in a pilot study involving eight participants prior to full deployment. Demographic variables included age, sex, geographic region of residence, marital status, and employment status. Clinical variables included height, pretreatment weight, weight loss, type of GLP-1 receptor agonist used, duration of treatment, and current treatment status. The primary outcome was participant-reported hair shedding following the initiation of medication. Secondary outcomes included hair shedding as a reason for treatment discontinuation, hair recovery following treatment cessation, and the occurrence of other adverse events across 12 symptom categories.
Variable Definitions
Hair shedding was defined as participant-reported increased hair loss occurring after the initiation of GLP-1 receptor agonist therapy, coded as a binary variable (yes/no). BMI was calculated as weight in kilograms divided by height in meters squared and categorized according to standard classifications: normal weight (<25.0 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2). Weight loss was calculated as the difference between the pre-treatment and current weight, with percentage weight loss computed as (weight lost to pre-treatment weight) × 100. Weight loss was subsequently categorized as <5%, 5–10%, 10–15%, and ≥15%. Duration of GLP-1 receptor agonist use was categorized as <1 month, 1–3 months, 4–6 months, 7–11 months, 1–2 years, and >2 years. Treatment was classified as ongoing or discontinued at the time of survey completion.
Statistical Analysis
Statistical analyses were performed using the R statistical software (version 4.3.0). Descriptive statistics were calculated for all variables, with categorical variables presented as frequencies and percentages and continuous variables as means with standard deviations or medians with interquartile ranges, as appropriate. Associations between hair shedding and potential risk factors were assessed using the chi-square test for categorical variables and independent t test for continuous variables. Fisher’s exact test was used when the expected cell counts were less than five. Statistical significance was set at p < 0.05. Multivariable logistic regression analysis was performed to identify independent predictors of hair shedding. Variables demonstrating associations (p < 0.20 in the univariate analysis were considered for inclusion in the initial multivariable model. Backward stepwise selection was used to develop the final parsimonious model. Results are presented as ORs with 95% CIs. Pearson’s correlation coefficients were calculated to examine the relationships between continuous variables, including BMI, absolute weight loss, and percentage weight loss.
Results
A total of 200 individuals were initially assessed; however, 3 participants who reported no use of weight loss medications were excluded, leaving 197 medication users. Among them, 8 individuals were excluded because they did not use GLP-1 receptor agonists, resulting in 189 GLP-1 users. Subsequently, 37 participants with preexisting hair loss before GLP-1 initiation were excluded, yielding a final analytic cohort of 152 individuals who used GLP-1 without a history of hair loss before treatment. The characteristics of the respondents are listed in Table 1.
Table 1.
Sample characteristics of GLP-1 users without preexisting hair loss (N = 152)
| Variable | n (%)/median [IQR] |
|---|---|
| Age-group | |
| 18–25 years | 23 (15.1) |
| 26–39 years | 82 (53.9) |
| 40–50 years | 41 (27.0) |
| 51+ years | 6 (3.95) |
| Gender | |
| Female | 133 (87.5) |
| Male | 19 (12.5) |
| Region of residence | |
| Central | 116 (76.3) |
| Eastern | 8 (5.26) |
| Northern | 5 (3.29) |
| Southern | 6 (3.95) |
| Western | 17 (11.2) |
| Marital status | |
| Divorced | 16 (10.5) |
| Married | 79 (52.0) |
| Single | 56 (36.8) |
| Widowed | 1 (0.66) |
| Employment status | |
| Employed | 99 (65.1) |
| Retired | 6 (3.95) |
| Student | 15 (9.87) |
| Unemployed | 32 (21.1) |
| Height, cm | 160 [156–165] |
| Weight before medication, kg | 84.0 [75.0–95.2] |
| BMI before treatment | 32.1 [29.4–37.2] |
| BMI category | |
| Overweight | 47 (30.9) |
| Obese | 105 (69.1) |
Categorical variables are presented as count (percentage); continuous variables as median [IQR].
The study sample included 152 GLP-1 users without preexisting hair loss (Table 1). Most were female (87.5%) and 26–39 years old (53.9%). The majority resided in the central region (76.3%), were married (52.0%), and were employed (65.1%). Median height was 160 cm [156–165], weight was 84.0 kg [75.0–95.2], and BMI was 32.1 [29.4–37.2]. Based on BMI, 30.9% were overweight and 69.1% were obese.
Among 152 GLP-1 users (Table 2), tirzepatide was the most frequently used medication (59.2%), followed by semaglutide (32.9%). Most participants used the medication for 1–6 months (66.4%) and over half had stopped treatment at the time of the survey (56.6%). The median weight loss was 13.0 kg [8.00–20.0], corresponding to a median weight loss percentage of 15.9% [8.69–22.5], with 53.3% achieving a loss of ≥15%. Hair shedding was reported by 70.4% of the users (n = 107).
Table 2.
Medication use, weight loss, and hair shedding among GLP-1 users (N = 152)
| Variable | n (%)/median [IQR] |
|---|---|
| Weight loss medication used | |
| Dulaglutide | 1 (0.66) |
| Liraglutide | 11 (7.24) |
| Semaglutide | 50 (32.9) |
| Tirzepatide | 90 (59.2) |
| Duration of medication use | |
| <1 month | 6 (3.95) |
| 1–3 months | 52 (34.2) |
| 4–6 months | 49 (32.2) |
| 7–11 months | 21 (13.8) |
| 1–2 years | 18 (11.8) |
| >2 years | 6 (3.95) |
| Currently using medication | |
| Still using | 66 (43.4) |
| Stopped | 86 (56.6) |
| Weight lost during treatment, kg | 13.0 [8.00–20.0] |
| Weight loss percentage | 15.9 [8.69–22.5] |
| Weight loss category | |
| <5% | 10 (6.58) |
| 5–10% | 31 (20.4) |
| 10–15% | 30 (19.7) |
| ≥15% | 81 (53.3) |
| Experienced hair shedding | 107 (70.4) |
| Hair shedding was a reason to discontinue | 27 (39.7% of 68) |
| Hair shedding stopped after discontinuation | 26 (37.7% of 68) |
| Noticed any other adverse events during use | 91 (59.9) |
Categorical variables are shown as count (percentage); continuous variables as median [IQR].
Percentages for subset variables reflect the number of “yes” responses among those to whom the question applied.
Among those who reported hair shedding and discontinued medication (n = 68), 39.7% (n = 27) identified it as a reason for stopping. Among those who stopped the medication and responded to the follow-up question (n = 68), 37.7% (n = 26) reported that hair shedding resolved after discontinuation (shown in Fig. 1).
Fig. 1.
Clinical outcomes in GLP-1 users. Percentages shown with (n/total) sample size.
A higher proportion of females was observed in the hair shedding group (92.5% vs. 75.6%, p = 0.009), and more participants who experienced shedding stopped their medication (63.6% vs. 40.0%, p = 0.013). Additionally, the weight loss category differed significantly between the groups (p = 0.002), with 62.6% of those with shedding achieving ≥15% weight loss compared to 31.1% in the no-shedding group. No significant group differences were found for age (p = 0.219), type or duration of medication used (p = 0.075 and p = 0.188, respectively), BMI before treatment (33.9 ± 7.47 vs. 33.3 ± 5.05, p = 0.589), total weight loss (p = 0.382), or percentage weight loss (p = 0.391). Among those who experienced hair shedding, tirzepatide users were over-represented (64.5% vs. 46.7% among non-shedders, p = 0.038). Other categorical variables, including region, marital status, and employment status, also showed no significant association with hair-shedding status (Table 3, p > 0.05).
Table 3.
Comparison of demographic and clinical characteristics between participants with and without hair shedding (N = 152)
| Variable | No shedding (n = 45), n (%) | Hair shedding (n = 107), n (%) | p value |
|---|---|---|---|
| Age-group | | | 0.219 |
| 18–25 years | 8 (17.8) | 15 (14.0) | |
| 26–39 years | 19 (42.2) | 63 (58.9) | |
| 40–50 years | 15 (33.3) | 26 (24.3) | |
| 51+ years | 3 (6.67) | 3 (2.80) | |
| Gender | | | 0.0091 |
| Female | 34 (75.6) | 99 (92.5) | |
| Male | 11 (24.4) | 8 (7.48) | |
| Weight loss medication used | | | 0.075 |
| Dulaglutide | 1 (2.22) | 0 (0.0) | |
| Liraglutide | 5 (11.1) | 6 (5.61) | |
| Semaglutide | 18 (40.0) | 32 (29.9) | |
| Tirzepatide | 21 (46.7) | 69 (64.5) | |
| Tirzepatide use | | | 0.0381 |
| Yes | 21 (46.7) | 69 (64.5) | |
| Other GLP-1 agonists | 24 (53.3) | 38 (35.5) | |
| Duration of use | | | 0.188 |
| <1 month | 4 (8.89) | 2 (1.87) | |
| 1–3 months | 18 (40.0) | 34 (31.8) | |
| 4–6 months | 14 (31.1) | 35 (32.7) | |
| 7–11 months | 3 (6.67) | 18 (16.8) | |
| 1–2 years | 4 (8.89) | 14 (13.1) | |
| >2 years | 2 (4.44) | 4 (3.74) | |
| Currently using medication | | | 0.0131 |
| Still using | 27 (60.0) | 39 (36.4) | |
| Stopped | 18 (40.0) | 68 (63.6) | |
| BMI before treatment | 33.3 (5.05) | 33.9 (7.47) | 0.589 |
| BMI category | | | 0.873 |
| Overweight | 13 (28.9) | 34 (31.8) | |
| Obese | 32 (71.1) | 73 (68.2) | |
| Weight lost, kg | 15.7 (20.1) | 18.7 (17.0) | 0.382 |
| Weight loss, % | 18.0 (23.7) | 21.4 (18.1) | 0.391 |
| Weight loss category | | | 0.0021 |
| <5% | 6 (13.3) | 4 (3.74) | |
| 5–10% | 14 (31.1) | 17 (15.9) | |
| 10–15% | 11 (24.4) | 19 (17.8) | |
| ≥15% | 14 (31.1) | 67 (62.6) | |
Continuous variables are shown as mean (SD).
Categorical variables as count (percentage).
p values based on chi-square or Fisher’s exact test for categorical variables; t test for continuous variables.
Missing values excluded pairwise.
1Statistically significant at p < 0.05.
Among the 91 participants who reported experiencing adverse events (shown in Fig. 2), the most frequently reported were gastrointestinal symptoms (54.9%, n = 50) and fatigue or energy-related issues (20.9%, n = 19). Systemic or other nonspecific complaints and neurological symptoms were reported by 14.3% (n = 13) of the patients. Psychological effects (11.0%, n = 10), skin/hair changes (9.9%, n = 9), and facial changes (7.7%, n = 7) were less frequently reported. Sexual/hormonal effects and appetite issues were reported by 4.4% of patients (n = 4).
Fig. 2.
Other adverse events reported by the respondents based on 91 participants who reported adverse events.
Hair shedding was most common with tirzepatide (76.7%), followed by semaglutide (64.0%) and liraglutide (54.5%), although the differences between medications were not statistically significant (p = 0.075). When examining shedding prevalence within each medication group, tirzepatide users had the highest rate (76.7%), followed by semaglutide (64.0%) and liraglutide (54.5%), though this comparison across all four medications did not reach statistical significance (p = 0.075), likely due to small sample sizes for liraglutide and dulaglutide. Shedding increased significantly with greater weight loss, reaching 82.7% in those who lost ≥15% of their weight (p = 0.002). Longer medication use (≥6 months) was associated with greater shedding (80% vs. 66.4%), but the difference was not significant (p = 0.137). No significant difference was observed in BMI category (p = 0.848, Fig. 3).
Fig. 3.
Hair shedding by GLP-1 medication (a), hair shedding by weight loss percentage (b), hair shedding by duration of use (c), Hair shedding by BMI category (d). Percentages reflect the proportion reporting hair shedding within each subgroup.
In the multivariable analysis of 152 GLP-1 users (Table 4), greater weight loss was significantly associated with a higher odds of experiencing hair shedding (OR = 1.79, 95% CI: 1.19–2.76, p = 0.006). Male participants had significantly lower odds of reporting hair shedding than females (OR = 0.28, 95% CI: 0.09–0.83, p = 0.023). Although participants younger than 40 years had higher odds of hair shedding (OR = 2.18, 95% CI: 0.95–5.03), this association was not statistically significant (p = 0.066). The use of tirzepatide (vs. other GLP-1s), treatment duration of ≥3 months, and BMI before treatment were not significantly associated with hair shedding (all p > 0.05).
Table 4.
Factors associated with hair shedding among GLP-1 users (N = 152)
| Predictor | OR | 95% CI | p value |
|---|---|---|---|
| Tirzepatide (ref: other GLP-1 RAs) | 1.62 | 0.74–3.57 | 0.226 |
| Duration ≥3 months (ref: <3 months) | 1.64 | 0.68–3.94 | 0.263 |
| Weight loss category1 (ordinal) | 1.79 | 1.19–2.76 | 0.0061 |
| BMI before treatment (continuous) | 1.03 | 0.98–1.10 | 0.317 |
| Age <40 years (ref: ≥40 years) | 2.18 | 0.95–5.03 | 0.066 |
| Male gender (ref: female) | 0.28 | 0.09–0.83 | 0.0231 |
OR and 95% CI derived from logistic regression.
Weight loss category was modeled as an ordinal variable (from <5% to ≥15%).
Reference categories are shown in parentheses.
1Statistically significant at p < 0.05.
Comparison of Weight Loss between Medication Types
To examine whether medication type independently predicted hair shedding, we compared weight loss between tirzepatide and semaglutide users. Weight loss did not differ significantly between groups (19.9% vs. 18.1%, p = 0.600; Table 5). In multivariable analysis adjusting for weight loss percentage, baseline BMI, sex, and age, the effect of tirzepatide versus semaglutide was attenuated and nonsignificant (adjusted OR 1.35, 95% CI: 0.59–3.04, p = 0.471), while weight loss percentage emerged as a significant independent predictor (OR 1.03 per 1% increase, 95% CI: 1.00–1.07, p = 0.044; Table 6). These findings suggest that the higher shedding prevalence observed with tirzepatide is explained by confounding factors, particularly sex distribution and weight loss magnitude, rather than a drug-specific effect.
Table 5.
Weight loss by medication type (tirzepatide vs. semaglutide)
| Variable | Semaglutide (N = 50) | Tirzepatide (N = 90) | p value |
|---|---|---|---|
| Weight loss, mean (SD), kg | 16.1 (19.3) | 17.5 (16.0) | 0.662 |
| Weight loss, mean (SD), % | 18.1 (20.2) | 19.9 (17.1) | 0.600 |
| Weight loss category, n (%) | | | 0.084 |
| <5% | 6 (12.0) | 4 (4.4) | |
| 5–10% | 11 (22.0) | 19 (21.1) | |
| 10–15% | 13 (26.0) | 14 (15.6) | |
| ≥15% | 20 (40.0) | 53 (58.9) | |
Table 6.
Effect of tirzepatide vs. semaglutide on hair shedding: unadjusted and adjusted models
| Predictor | Unadjusted OR (95% CI) | p value | Weight-adj OR | p value | Fully adj OR | p value |
|---|---|---|---|---|---|---|
| Tirzepatide (ref: semaglutide) | 1.85 (0.86–3.95) | 0.111 | 1.78 (0.82–3.83) | 0.142 | 1.35 (0.59–3.04) | 0.471 |
| Weight loss (%) | — | — | 1.02 (1.00–1.06) | 0.128 | 1.03 (1.00–1.07) | 0.044 |
| BMI before treatment | — | — | — | — | 1.03 (0.97–1.11) | 0.337 |
| Male sex (ref: female) | — | — | — | — | 0.24 (0.08–0.72) | 0.011 |
| Age <40 years (ref: ≥40) | — | — | — | — | 2.32 (0.96–5.66) | 0.061 |
Model based on n = 140 participants using tirzepatide or semaglutide.
Bold p values indicate statistical significance.
Discussion
The present study provides robust evidence that hair shedding is a frequent and clinically relevant phenomenon reported during GLP-1 RA treatment in Saudi Arabia, with 70.4% of participants reporting this outcome and over one-third identifying it as a reason for discontinuation. These findings echo recent pharmacovigilance analyses that identified a statistically significant signal for alopecia with semaglutide and tirzepatide but not older GLP-1 RAs, such as liraglutide or dulaglutide. Godfrey et al. reported ORs of 2.46 for semaglutide and 1.73 for tirzepatide in FAERS data, confirming disproportionate associations with alopecia [13]. Similarly, Nakhla et al. [17] showed elevated, though not yet signal-level, hair loss across four major pharmacovigilance systems. In addition, a recent retrospective cohort confirmed a higher alopecia risk among semaglutide users, underscoring that hair loss is not a coincidental observation but a reproducible finding across databases and study designs [14].
Consistent with our study, in which female users reported significantly more hair shedding than males (92.5% vs. 75.6%), global data confirm disproportionate vulnerability among women. A large claims-based cohort found that women using semaglutide had more than twice the risk of alopecia compared to active comparators, whereas men showed no significant increase [14]. Similarly, sex-specific pharmacovigilance patterns show that the majority of adverse event reporters are female, with up to 68.8% of tirzepatide-associated cutaneous AEs observed in women [15]. This disparity may reflect a true biological predisposition, potentially linked to hormonal fluctuations and greater susceptibility to TE, but may also be partially explained by reporting bias given the cosmetic implications of alopecia.
The relationship between rapid weight loss and hair shedding has been well documented across multiple modalities. Our findings that individuals with ≥15% weight reduction had significantly higher hair shedding risk mirror patterns seen in bariatric surgery patients, where up to 50–60% develop TE within 3–6 months post-surgery, largely driven by nutritional deficiencies and acute metabolic stress [19–21]. Clinical trial data further reinforce this mechanism: in SURMOUNT-1, alopecia incidence increased with the degree of weight loss but not drug dosage. Specifically, the SURMOUNT-1 trial data showed alopecia rates of 5.08% (5 mg), 4.87% (10 mg), and 5.71% (15 mg) tirzepatide versus 0.93% placebo, with hair loss correlating with the degree of weight loss rather than the drug dosage [22]. Şen and Türkçapar (2021) found a 72% hair loss prevalence in 156 female sleeve gastrectomy patients, with 79% experiencing onset between months 3–4 and an average duration of 5.5 ± 2.6 months, providing a useful comparison for GLP-1-induced patterns [23].
Biological underpinning is thought to involve disruption of the hair follicle cycle secondary to metabolic stress. Evidence suggests that GLP-1 receptors are expressed in murine hair follicles, but whether human follicular GLP-1R signaling directly modulates hair growth remains unclear [13]. Therefore, it is more plausible that drug-induced rapid catabolic states act as triggers for TE rather than direct follicular toxicity [24]. Our findings are consistent with weight-loss-mediated TE rather than a direct pharmacological effect of GLP-1 receptor agonists on hair follicles.
Our adjusted analyses demonstrated that the apparent difference in hair shedding between tirzepatide and semaglutide users was fully attenuated after controlling for weight loss magnitude, sex, and age, with weight loss percentage emerging as an independent predictor. This finding aligns with the well-documented phenomenon of TE following rapid weight reduction, as observed in bariatric surgery cohorts, and supports a weight-loss-mediated rather than direct pharmacological mechanism.
Importantly, our real-world prevalence of hair shedding was substantially higher than the rates reported in randomized trials, where alopecia was noted in only 3–7% of participants. This discrepancy highlights the underreporting of adverse cosmetic events in the controlled studies. For example, in SURMOUNT-1, alopecia was reported in only 4–6% of tirzepatide users, despite significantly greater weight loss compared with placebo [25]. Conversely, observational studies have consistently reported much higher discontinuation rates due to tolerability, with dermatologic manifestations among the contributing factors [26]. This gap between trial data and real-world experience underscores the necessity of pharmacovigilance and patient-reported outcomes to fully capture the clinical burden of hair loss associated with GLP-1 therapy.
Another plausible explanation for hair shedding observed during GLP-1 RA therapy is nutrient deficiency secondary to a reduced dietary intake. Patients with GLP-1 RAs frequently exhibit deficits in protein, iron, zinc, and vitamin D levels, which are critical to hair follicle health. A recent study documented that nearly 90% of GLP-1 users had a protein intake below the recommended threshold, with iron and vitamin D deficiencies nearly universally [13]. Johnson et al. [27] (2025) provided more granular data, documenting alarming deficiency rates in 69 GLP-1 users: 98.6% vitamin D deficiency, 88.4% iron deficiency, 89.9% magnesium deficiency, and 75% consuming inadequate protein (<1.2 g/kg/day needed during weight loss). Mozaffarian et al. [28] (2025) published joint nutritional priorities from major organizations, emphasizing that GLP-1 users lose 20–50% lean body mass and require 1.2–2.0 g/kg daily protein versus 0.8 g/kg RDA.
These nutritional factors may explain the high prevalence of hair shedding in the Saudi cohort. Ruiz-Tovar et al. [29] (2014) demonstrated that combined zinc and iron levels <115 predicted hair loss after sleeve gastrectomy with 88% sensitivity and 84% specificity. Guo and Katta [30] (2017) systematically reviewed nutritional factors in hair loss, confirming that iron deficiency is the most common nutritional cause, with protein malnutrition showing threshold effects. Similar associations have long been observed in bariatric cohorts, where deficiencies strongly predict TE [16]. Given that our study population from Saudi Arabia likely had high baseline rates of vitamin D deficiency, which affects up to 80% of adults in the region [27], the combination of preexisting deficiencies and GLP-1-induced reduced intake may synergistically increase hair loss risk. Therefore, ensuring adequate dietary protein (≥1.2 g/kg/day) and micronutrient supplementation may mitigate the risk of hair shedding, offering a practical intervention strategy for clinical management [31].
Regional and global data indicate that the burden of GLP-1, an underlying epidemiological and nutritional factor, may amplify the associated hair loss. In the Middle East, where obesity prevalence among women reaches up to 55% in some Gulf countries and vitamin D deficiency affects as many as 80% of adults, the combination of rapid weight loss and preexisting micronutrient deficiency likely predisposes patients to higher rates of TE [32, 33]. Our Saudi Arabian cohort contributes uniquely to this gap, documenting a 70% prevalence of hair shedding among GLP-1 users, far exceeding the rates reported in North American clinical trials, where alopecia incidence is typically below 10% [25].
Substantial discrepancies exist between controlled trial settings and real-world usage patterns [34]. Thomsen et al. [35] (2025) documented real-world discontinuation rates of 20–50% within the first year versus 14.2–17.1% in clinical trials, with cosmetic side effects likely underreported in structured trial assessments. Rodriguez et al. [34] (2025) analyzed 125,474 adults across 30 US health systems, finding 53.6% 1-year discontinuation and 72.2% 2-year discontinuation, with gastrointestinal adverse events increasing the discontinuation risk (HR: 1.38 with diabetes, 1.19 without). Importantly, global pharmacovigilance networks consistently reveal geographic clustering of hair loss reports, particularly in high-prescription markets such as the US, Brazil, and Saudi Arabia, with women comprising the majority of cases [36]. These regional variations underscore that hair loss risk with GLP-1 agonists is not uniform but is shaped by baseline nutritional status, sex-specific factors, and prescribing patterns, highlighting the need for region-specific surveillance and dietary guidance to optimize safe use.
The clinical implications of our findings – 70.4% hair shedding prevalence with 39.7% citing it as a reason for discontinuation – demand a paradigm shift in GLP-1 RA management. While this TE typically resolves within 6–12 months, aligning with the recovery patterns documented in the STEP 1 Extension Trial [37], the psychosocial burden remains substantial, particularly in Middle Eastern populations where hair carries cultural significance. Proactive management should include pre-treatment screening for ferritin, vitamin D, zinc, and thyroid function, as recommended by Almohanna et al. [38]. During treatment, monthly monitoring through the rapid weight loss phase should focus on protein optimization (1.2–2.0 g/kg/day) and targeted supplementation. For patients experiencing significant shedding, extending dose titration periods to minimize weight loss velocity may prove beneficial, according to the recent Obesity Medicine Association guidelines [11]. Dermatology referral remains warranted for persistent shedding beyond 6 months or atypical patterns, suggesting alternative diagnoses.
Future research must address key gaps, including prospective studies using trichoscopy and standardized hair pull tests for objective quantification of hair shedding, genetic polymorphism investigations examining individual susceptibility, and randomized trials of preventive supplementation protocols, as advocated by Desai et al. [12]. Trichoscopic parameters such as the proportion of vellus hairs, empty follicles, and peripilar signs would provide objective endpoints less susceptible to reporting bias and would enable differentiation between TE and other forms of alopecia. Prospective studies should incorporate structured follow-up assessments to characterize the natural history and time course of hair shedding resolution following GLP-1 RA discontinuation or dose stabilization. As GLP-1 RAs transition from diabetes management to cosmetic weight loss, tolerance for cosmetic adverse effects paradoxically decreases, demanding novel strategies, including modified-release formulations or combination products with hair-protective nutrients, similar to the approaches suggested by Buontempo and Santos [13] (2025) in their analysis of emerging GLP-1 complications. The hair shedding phenomenon serves as a sentinel event, demonstrating that patient-centered outcomes must drive both drug development and clinical practice to ensure treatment persistence in addressing the global obesity pandemic.
Limitations
This study has several limitations that merit consideration. First, the cross-sectional design precludes causal inference, thus preventing the establishment of temporal relationships between GLP-1 use and hair shedding. Second, self-reported hair loss without clinical verification (trichoscopy, pull tests) may introduce recall bias and subjective interpretation, particularly given the increased social media awareness of this side effect. Third, convenience sampling via online platforms likely created a selection bias, preferentially capturing individuals with adverse events, potentially explaining our 70.4% prevalence versus 3–7% in trials. Excluding 37 participants with preexisting hair loss, those with undiagnosed TE exacerbated by GLP-1 therapy may have been excluded.
Fourth, the absence of a control group that underwent comparable weight loss through other modalities limits the differentiation between drug-specific and weight loss-related effects. We lacked detailed nutritional data, baseline laboratory results, and concurrent medication information to prevent adjustment for these confounders. Fifth, although 37.7% of participants reported resolution of hair shedding after treatment discontinuation, we did not collect data on the time interval between discontinuation and resolution. Given that the hair follicle cycle spans several months and TE typically resolves over 6–12 months, precise temporal assessment would require prospective follow-up with standardized time points. Self-reported resolution timing would be subject to considerable recall bias. Finally, our sample’s gender imbalance (87.5% female) and Saudi-specific recruitment limits generalizability, while regional cultural factors may heighten hair loss awareness and reporting.
Conclusion
GLP-1 receptor agonist-associated hair shedding represents a critical gap between clinical trial efficacy and real-world tolerability, which threatens treatment persistence. Although medically benign and reversible, this cosmetic adverse effect carries a substantial psychosocial burden, particularly as these medications transition from diabetes management to lifestyle use. Clinicians must shift from reactive to proactive management by implementing pretreatment nutritional screening and prophylactic supplementation protocols. This phenomenon highlights the broader challenges in pharmaceutical development, where quality of life outcomes remain inadequately captured in registration trials. Successful deployment of GLP-1 agonists in combating global obesity requires recognition of patient-centered outcomes, not just metabolic endpoints, to determine long-term therapeutic success.
Acknowledgment
The researchers would like to thank the Deanship of Graduate Studies and Scientific Research at Qassim University for financial support (QU-APC-2026).
Statement of Ethics
This study protocol was reviewed and approved by Committee of Research Ethics, Deanship of Graduate Studies and Scientific Research, Qassim University, Approval No. 25-43-03. Written informed consent was obtained from participants to participate in the study.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This study was not supported by any sponsor or funder; only conditional support for publication fees was provided by Qassim University.
Author Contributions
S.A. and A.A. contributed equally to the conception, design, data collection, analysis, and writing of the manuscript.
Funding Statement
This study was not supported by any sponsor or funder; only conditional support for publication fees was provided by Qassim University.
Data Availability Statement
All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.
References
- 1. Phelps NH, Singleton RK, Zhou B, Heap RA, Mishra A, Bennett JE. Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. Lancet. 2024;403:1027–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Ghiya P. How does obesity effect cardiovascular disease. Multidiscip Rev. 2024;8(4):2025119. [Google Scholar]
- 3. Dal Canto E, Ceriello A, Rydén L, Ferrini M, Hansen TB, Schnell O, et al. Diabetes as a cardiovascular risk factor: an overview of global trends of macro and micro vascular complications. Eur J Prev Cardiol. 2019;26:25–32. [DOI] [PubMed] [Google Scholar]
- 4. Lobstein T, Powis J, Jackson-Leach R. World Obesity Atlas 2024. 2024. p. 236. [Google Scholar]
- 5. Petroni ML, Caletti MT, Calugi S, Dalle Grave R, Marchesini G. Long-term treatment of severe obesity: are lifestyle interventions still an option? Expert Rev Endocrinol Metab. 2017;12(6):391–400. [DOI] [PubMed] [Google Scholar]
- 6. Machado AM, Guimarães NS, Bocardi VB, da Silva TPR, Carmo AS, Menezes MC, et al. Understanding weight regain after a nutritional weight loss intervention: systematic review and meta-analysis. Clin Nutr ESPEN. 2022;49:138–53. [DOI] [PubMed] [Google Scholar]
- 7. Sarma S, Palcu P. Weight loss between glucagon-like peptide-1 receptor agonists and bariatric surgery in adults with obesity: a systematic review and meta-analysis. Obesity. 2022;30:2111–21. [DOI] [PubMed] [Google Scholar]
- 8. Østergaard L, Frandsen CS, Madsbad S. Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review. Expert Rev Clin Pharmacol. 2016;9:241–65. [DOI] [PubMed] [Google Scholar]
- 9. Madsbad S, Holst JJ. The promise of glucagon-like peptide 1 receptor agonists (GLP-1RA) for the treatment of obesity: a look at phase 2 and 3 pipelines. Expert Opin Investig Drugs. 2025;34:197–215. [DOI] [PubMed] [Google Scholar]
- 10. Maan S, Sohail AH, Sulaiman SA, Mansoor L, Cohen EM, Adekolu AA, et al. Metabolic and bariatric surgery versus glucagon-like peptide-1 receptor agonist therapy: a comparison of cardiovascular outcomes in patients with obesity. Am J Surg. 2025;242:116242. [DOI] [PubMed] [Google Scholar]
- 11. Gorgojo-Martínez JJ, Mezquita-Raya P, Carretero-Gómez J, Castro A, Cebrián-Cuenca A, de Torres-Sánchez A, et al. Clinical recommendations to manage gastrointestinal adverse events in patients treated with Glp-1 receptor agonists: a multidisciplinary expert consensus. J Clin Med. 2023;12(1):145. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. Desai DD, Sikora M, Nohria A, Bordone L, Caplan AS, Shapiro J, et al. GLP-1 agonists and hair loss: a call for further investigation. Int J Dermatol. 2024;63(9):1128–30. [DOI] [PubMed] [Google Scholar]
- 13. Buontempo MG, Santos BT. Exploring the hair loss risk in glucagon-like peptide-1 agonists: emerging concerns and clinical implications. J Eur Acad Dermatol Venereol. 2025;39(2):263–4. [DOI] [PubMed] [Google Scholar]
- 14. Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of hair loss with semaglutide for weight loss. medRxiv. 2025. [Google Scholar]
- 15. Burke OM, Sa B, Cespedes DA, Tosti A. Dermatologic Implications of Glucagon-Like Peptide-1 Receptor Agonist Medications. Skin Appendage Disord. 2025;11(5):416–23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Zhang W, Fan M, Wang C, Mahawar K, Parmar C, Chen W, et al. Hair loss after metabolic and bariatric surgery: a systematic review and meta-analysis. Obes Surg. 2021;31(6):2649–59. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Nakhla M, Nair A, Balani P, Ujjawal A, Arun Kumar P, Dasari M, et al. Risk of suicide, hair loss, and aspiration with GLP1-Receptor agonists and other diabetic agents: a real-world pharmacovigilance study. Cardiovasc Drugs Ther. 2025;39(6):1331–41. [DOI] [PubMed] [Google Scholar]
- 18. Do D, Lee T, Peasah SK, Good CB, Inneh A, Patel U. GLP-1 receptor agonist discontinuation among patients with obesity and/or type 2 diabetes. JAMA Netw Open. 2024;7(5):e2413172. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Andrade IDM, Vitoretti M, Caliman GC, Mota DF, Silva GT, Carneiro ACWA, et al. Telogen effluvium in patients after bariatric surgery: a scoping review. Braz J Clin Med Rev. 2025;3(1):bjcmr9. [Google Scholar]
- 20. Cohen-Kurzrock RA, Cohen PR. Bariatric surgery-induced telogen effluvium (Bar SITE): case report and a review of hair loss following weight loss surgery. Cureus. 2021;13(4):e14617. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. O’Kane M, Parmar C. Letter to editor concerning: global bariatric research collaborative. Hair loss after metabolic and bariatric surgery: a systematic review and meta-analysis. Obes Surg. 2021;31:3337–8. [DOI] [PubMed] [Google Scholar]
- 22. Opalska L, Muciek A, Mocarska M, Orłowska A, Strakowska K, Maryńczak A, et al. Insights into the efficacy of GLP-1 agonists and dual agonists: semaglutide and tirzepatide in obesity and type 2 diabetes. Qual Sport. 2024;35:56425. [Google Scholar]
- 23. Smolarczyk K, Meczekalski B, Rudnicka E, Suchta K, Szeliga A. Association of obesity and bariatric surgery on hair health. Med. 2024;60(2):325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. Arck PC, Handjiski B, Peters EMJ, Peter AS, Hagen E, Fischer A, et al. Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways. Am J Pathol. 2003;162(3):803–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Baran K, Jankowska M, Jańczyk N, Mędrysa K, Pokrzepa J, Presak M, et al. Semaglutide, liraglutide and tirzepatide: comparison of effectiveness in the treatment of obesity: a literature review. Qual Sport. 2024;30:56469. [Google Scholar]
- 26. Daniel S, Waggett S, Lyles E, Sagut P, Shamaei Zadeh P, Marcelletti A, et al. A retrospective comparative analysis of cutaneous adverse reactions in GLP-1 agonist therapies. J Drugs Dermatol. 2025;24(4):413–5. [DOI] [PubMed] [Google Scholar]
- 27. Johnson B, Milstead M, Thomas O, McGlasson T, Green L, Kreider R, et al. Investigating nutrient intake during use of glucagon-like peptide-1 receptor agonist: a cross-sectional study. Front Nutr. 2025;12:1566498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Mozaffarian D, Agarwal M, Aggarwal M, Alexander L, Apovian CM, Bindlish S, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint advisory from the American College of Lifestyle medicine, the American society for Nutrition, the obesity medicine Association, and the Obesity society. Am J Clin Nutr. 2025;122(1):344–67. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Ruiz-Tovar J, Oller I, Llavero C, Zubiaga L, Diez M, Arroyo A, et al. Hair loss in females after sleeve gastrectomy: predictive value of serum zinc and iron levels. Am Surg. 2014;80(5):466–71. [PubMed] [Google Scholar]
- 30. Guo EL, Katta R. Diet and hair loss: effects of nutrient deficiency and supplement use, Dermatol. Pract Concept. 2017;7:1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31. Rajput R. Influence of nutrition, food supplements and lifestyle in hair disorders. Indian Dermatol Online J. 2022;13(6):721–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. ALNohair S. Obesity in gulf countries. Int J Health Sci. 2014;8(1):79–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33. Lips P, Cashman KD, Lamberg-Allardt C, Bischoff-Ferrari HA, Obermayer-Pietsch B, Bianchi ML, et al. Current Vitamin D status in European and Middle East countries and strategies to prevent Vitamin D deficiency: a position statement of the European calcified tissue society. Eur J Endocrinol. 2019;180(4):P23–54. [DOI] [PubMed] [Google Scholar]
- 34. Rodriguez PJ, Zhang V, Gratzl S, Do D, Goodwin Cartwright B, Baker C, et al. Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists among US adults with overweight or obesity. JAMA Netw Open. 2025;8(1):e2457349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Thomsen RW, Mailhac A, Løhde JB, Pottegård A. Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies, diabetes. Obes Metab. 2025;27(Suppl 2):66–88. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36. Chiappini S, D’andrea G, Cavallotto C, Mosca A, Carlo FD, Pettorruso M, et al. Pharmacovigilance signals of semaglutide and other Glp-1 receptor agonists: an analysis of the food and Drug Administration (Fda) adverse events reporting System (Faers) dataset. Int J Neuropsychopharmacol. 2025;28(Supplement_1):i300. [Google Scholar]
- 37. Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension, diabetes. Obes Metab. 2022;24(8):1553–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38. Almohanna HM, Ahmed AA, Tsatalis JP, Tosti A. The role of vitamins and minerals in hair loss: a review. Dermatol Ther. 2019;9(1):51–70. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated or analyzed during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.