Nonapproved Retatrutide Users on Reddit Report Appetite and Fatigue Symptoms

Increased appetite, fatigue, and increased energy were among the most common self-reported symptoms among social media users who described personally using nonapproved retatrutide. The findings come from a cross-sectional research letter published in JAMA Network Open.

The authors described retatrutide as an investigational once-weekly agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 (GLP-1), and glucagon receptors. They noted that the FDA has warned that nonapproved retatrutide products are being sold directly to consumers, including products labeled for research or not for human consumption.

The investigators analyzed 148,640 retatrutide-related Reddit posts and comments from 27 communities, posted between May 2021 and December 2025. They used large language models to identify posts describing personal use and to map the symptoms people reported to Medical Dictionary for Regulatory Activities preferred terms. Of 13,589 users reporting current use, 7823 reported at least 1 mapped symptom once prespecified weight-loss and appetite-suppression terms were excluded. Among these users, the most frequently reported terms were increased appetite (17.1%), fatigue (15.2%), increased energy (12.4%), nausea (11.6%), food craving (7.3%), insomnia (6.1%), and increased heart rate (4.8%).

The investigators also compared their results descriptively with a prior social media study of semaglutide and tirzepatide. Retatrutide discussions were more concentrated in appetite, general-system, muscle-related, sleep, and heart-rate categories. Semaglutide and tirzepatide discussions were more concentrated in nausea, vomiting, and gastrointestinal motility categories. The samples were not matched, and no statistical comparisons were performed. The authors said these patterns may reflect unmeasured cohort differences rather than pharmacologic effects. They added that reported events may also relate to product or dose variability, peptide stacking, or misattribution.

The authors described the findings as hypothesis-generating. Product identity, purity, dose, and users’ medical histories could not be verified. As a result, the analysis cannot assess incidence, causality, dose-response, or comparative safety vs approved GLP-1 receptor agonists. They said prospective studies are needed to determine whether these signals represent true pharmacological effects.

Source: Sehgal NKR, Tronieri JS, Rader B, Ungar L, Guntuku SC. Self-reported adverse effects among social media users taking nonapproved retatrutide. JAMA Netw Open. 2026;9(10):e2638929. doi:10.1001/jamanetworkopen.2026.38929