Starvation ketosis following self-administered tirzepatide obtained via online services in a young woman later diagnosed with anorexia nervosa: a case report

Starvation ketosis following self-administered tirzepatide obtained via online services in a young woman later diagnosed with anorexia nervosa: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Starvation ketosis following self-administered tirzepatide obtained via online services in a young woman later diagnosed with anorexia nervosa: a case report Norio Yasui-Furukori, Kasumi Tasaki, Yusuke Kaiga, Yoshimasa Aso This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9289959/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, induces potent appetite suppression and substantial weight loss. Increasing access to incretin-based therapies through online services has raised concerns regarding metabolic and psychiatric complications, particularly in vulnerable individuals. We report a case of starvation ketosis associated with self-administered tirzepatide, followed by the clinical recognition of anorexia nervosa. Case presentation: A 21-year-old woman with no prior formal psychiatric or metabolic diagnoses had a history of dieting behaviors and intermittent binge-purge episodes. Seeking further weight loss, she obtained tirzepatide through online medical services and self-administered 2.5 mg weekly for approximately four weeks, followed by 5.0 mg weekly for another month, without direct medical supervision. Her body weight decreased from 47 kg to 41 kg (BMI 17.9 to 15.6 kg/m²). Approximately two months after initiation, she developed severe nausea, bilious vomiting, and presyncope, requiring emergency admission. Laboratory evaluation revealed marked ketonemia (serum 3-hydroxybutyrate 2057 µmol/L), normoglycemia (glucose 79 mg/dL), mildly elevated anion gap, normal HbA1c (5.1%), and no clinically significant acidemia. She had no history of SGLT2 inhibitor use or habitual alcohol consumption. She was diagnosed with starvation ketosis and improved with intravenous glucose infusion and nutritional support. Shortly after discharge, psychiatric evaluation led to a diagnosis of anorexia nervosa. At early follow-up, body weight had increased to 42 kg, the Eating Attitudes Test-26 (EAT-26) score decreased to 14, but serum 3-hydroxybutyrate remained elevated at 166 µmol/L. At later outpatient reassessment several months later, body weight remained 42 kg, serum 3-hydroxybutyrate had normalized to 24 µmol/L, and the EAT-26 score was 16; however, her drive for thinness persisted. Conclusions This case highlights that unsupervised tirzepatide use may be associated with starvation ketosis and the clinical recognition or exacerbation of eating-disorder psychopathology. Metabolic recovery did not parallel full improvement in eating-disorder symptoms, underscoring the need for careful screening, longitudinal psychiatric follow-up, and interdisciplinary management when incretin-based therapies are used. tirzepatide starvation ketosis anorexia nervosa GLP-1 receptor agonist self-medication eating disorder Introduction Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GIP/GLP-1 receptor agonists have transformed the management of obesity and type 2 diabetes through potent appetite suppression, delayed gastric emptying, and marked weight reduction [ 1 , 2 ]. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has demonstrated superior weight reduction compared with semaglutide in a head-to-head phase 3b trial in adults with obesity [ 1 ]. Alongside their expanding clinical use, access to incretin-based agents through online services has raised concerns about use without adequate longitudinal supervision. Emerging reviews suggest that GLP-1RAs may improve, maintain, or worsen eating-disorder symptoms depending on the clinical context, underscoring the need for caution in vulnerable individuals [ 3 , 4 , 10 ]. Starvation ketosis is a metabolic condition characterized by elevated ketone bodies resulting from prolonged caloric restriction, typically in the absence of hyperglycemia or severe acidemia. Although uncommon, it represents a clinically important complication of extreme weight loss. Here, we describe a case of starvation ketosis following unsupervised tirzepatide use, after which anorexia nervosa was clinically recognized. Case presentation The patient was a 21-year-old woman with no documented formal psychiatric or metabolic disorders. At the age of 18 years, her body weight was 56 kg. She had engaged in dieting behaviors, including reducing meal frequency from three to two meals per day, as well as recurrent binge eating followed by self-induced vomiting. Although these behaviors were not previously evaluated psychiatrically, her desire for further weight loss persisted. In mid-2025, seeking additional weight reduction, she obtained tirzepatide (Mounjaro®) through online medical services and initiated self-injection without direct medical supervision. The initial dose was 2.5 mg once weekly for approximately four weeks, after which the dose was increased to 5.0 mg once weekly. At the start of tirzepatide administration (Month 0), her body weight was 47 kg. Over the subsequent two months, her weight decreased to 41 kg at a height of 162 cm, corresponding to a reduction in body mass index (BMI) from 17.9 kg/m² to 15.6 kg/m², representing an approximate 12.8% loss of body weight. Approximately two months after initiating tirzepatide, she developed severe nausea, repeated bilious vomiting, and presyncope with difficulty maintaining an upright posture, which led to emergency admission. Laboratory investigations at admission revealed a markedly elevated serum 3-hydroxybutyrate level of 2057 µmol/L, indicating significant ketonemia. Plasma glucose was 79 mg/dL, HbA1c was 5.1%, and there was no history of SGLT2 inhibitor use or habitual alcohol consumption. Serum electrolytes were as follows: sodium 141 mmol/L, potassium 3.8 mmol/L, and chloride 100 mmol/L. The anion gap was 16.9 mmol/L when calculated without potassium (20.5 mmol/L including potassium). Venous blood gas analysis demonstrated a pH of 7.437, partial pressure of carbon dioxide of 36.4 mmHg, bicarbonate of 24.0 mmol/L, and a base excess of 0.3 mmol/L, indicating the absence of clinically significant acidemia. Serum lactate was 2.4 mmol/L, excluding clinically relevant lactic acidosis. In the context of marked ketonemia, normoglycemia, mildly elevated anion gap, recent rapid weight loss, reduced oral intake, and no SGLT2 inhibitor exposure, she was diagnosed with starvation ketosis rather than diabetic ketoacidosis. Treatment consisted of intravenous glucose-containing fluids and electrolyte replacement, followed by gradual reintroduction of oral intake. Her gastrointestinal symptoms and general condition improved, and she was discharged after several days of inpatient care. The clinical course is summarized in Table 1. Shortly after discharge, psychiatric evaluation was performed because of persistent anxiety related to eating and an intense fear of weight gain. At that time, her body weight remained 41 kg (BMI 15.6 kg/m²). Psychological assessment revealed a pronounced drive for thinness, body-image distortion, and restrictive eating behavior. Based on DSM-5 criteria, she was diagnosed with anorexia nervosa. The Eating Attitudes Test-26 (EAT-26) score was 22, exceeding the conventional cut-off score of 20 suggestive of an eating disorder. Psychoeducation and nutritional counseling were initiated, and regular psychiatric follow-up was arranged. At early outpatient follow-up, her body weight had increased to 42 kg. Serum 3-hydroxybutyrate remained elevated at 166 µmol/L (reference range, 0–74 µmol/L), while the EAT-26 score had decreased to 14. At a later outpatient reassessment several months later, her body weight remained 42 kg (BMI 16.0 kg/m²). Serum 3-hydroxybutyrate had normalized to 24 µmol/L, whereas the EAT-26 score was 16. Although ketonemia had resolved, her drive for thinness persisted. She continues to receive outpatient psychiatric follow-up. Discussion This case illustrates a clinically significant intersection of metabolic and psychiatric pathology: starvation ketosis temporally associated with unsupervised tirzepatide use in a young woman later diagnosed with anorexia nervosa. The case is notable not only because of the metabolic complication itself, but also because metabolic improvement did not parallel full psychiatric improvement. GLP-1/GIP receptor agonists and eating behavior Tirzepatide exerts its effects through combined GIP and GLP-1 receptor agonism, producing marked appetite suppression and changes in ingestive behavior [ 5 ]. Although incretin-based therapies are effective for obesity treatment, reviews of GLP-1 receptor agonists in eating-disorder populations emphasize that these agents may improve, maintain, or worsen eating-disorder symptoms depending on patient characteristics and treatment context [ 3 , 4 , 10 ]. This bidirectional potential is especially relevant in patients with pre-existing disordered-eating behaviors or strong weight-related psychopathology. Recent case reports describe semaglutide misuse in atypical anorexia nervosa and relapse of anorexia nervosa associated with tirzepatide [ 6 , 7 ]. Pharmacovigilance data have also suggested signals for psychiatric adverse events with GLP-1 receptor agonists, although such data do not establish causality [ 8 , 9 ]. Taken together, these findings support the view that incretin-based therapies should not be considered purely metabolic agents, but rather drugs with potential psychobehavioral effects in susceptible individuals. Starvation ketosis without clinically significant acidemia The present case is notable for marked ketonemia (serum 3-hydroxybutyrate 2057 µmol/L) without clinically significant acidemia. The diagnosis of starvation ketosis was supported by normoglycemia (79 mg/dL), normal HbA1c (5.1%), absence of SGLT2 inhibitor exposure or habitual alcohol consumption, and a mildly elevated anion gap, in addition to recent rapid weight loss and reduced oral intake. Starvation ketosis arises from glycogen depletion and enhanced fatty-acid oxidation during prolonged caloric restriction, typically with normal or low blood glucose levels. Unlike diabetic ketoacidosis, the acid-base disturbance may be mild or absent, particularly when assessment occurs early or after partial compensation. In this patient, the combination of substantial recent weight loss, reduced oral intake, gastrointestinal symptoms, normoglycemia, and marked ketonemia supported starvation ketosis rather than diabetic ketoacidosis. Clinicians should therefore consider measuring serum ketones in patients receiving incretin-based therapies who present with nausea, vomiting, malaise, or presyncope, even in the absence of overt acidemia. Psychiatric implications A central psychiatric implication of this case is that tirzepatide-associated appetite suppression and rapid weight loss likely interacted with pre-existing dieting behavior and may have contributed to the clinical recognition or worsening of eating-disorder psychopathology rather than unequivocal de novo onset of anorexia nervosa. The patient had engaged in dieting and binge-purge behavior before tirzepatide initiation, suggesting pre-existing vulnerability. However, the temporal association between self-administered tirzepatide, rapid weight loss, medical decompensation, and subsequent psychiatric diagnosis is clinically meaningful. GLP-1 signaling influences reward-related and motivational pathways, and pharmacologically induced weight loss may function as a strong reinforcer for restrictive eating in vulnerable individuals [ 3 , 5 , 10 ]. In this context, the medication may have amplified pre-existing cognitive and behavioral tendencies centered on thinness, control, and fear of weight gain. Interpretation of EAT-26 scores during follow-up The longitudinal EAT-26 findings in this case warrant cautious interpretation. Although the score decreased from 22 at initial psychiatric evaluation to 14 at early follow-up, and was 16 at later follow-up, these values should not be interpreted as evidence of remission. The EAT-26 was originally developed as a screening and case-finding instrument rather than a diagnostic tool [ 11 ]. The conventional threshold of 20 is intended to identify individuals who require further professional evaluation, but scores below 20 do not exclude clinically significant eating-disorder psychopathology. Moreover, a recent case-control study in Japan suggested that an optimal cut-off score for DSM-5 eating disorders may be lower, at 17 [ 12 ]. In the present case, therefore, the decline in EAT-26 scores likely reflects partial improvement in self-reported symptoms rather than full psychiatric recovery. Divergence between metabolic and psychiatric recovery A particularly important feature of this case is that normalization of ketone levels did not coincide with full improvement in eating-disorder psychopathology. At early outpatient follow-up, serum 3-hydroxybutyrate remained elevated at 166 µmol/L despite an increase in body weight to 42 kg and a reduction in EAT-26 score from 22 to 14. At later follow-up, serum 3-hydroxybutyrate had normalized to 24 µmol/L, but her body weight remained 42 kg and her drive for thinness persisted; the EAT-26 score also remained elevated at 16. These findings suggest that metabolic stabilization after starvation ketosis does not necessarily indicate remission of the underlying eating disorder. Clinicians should therefore interpret improvement in biochemical parameters or questionnaire scores cautiously and continue longitudinal psychiatric assessment, particularly in patients whose weight restoration remains limited and whose overvaluation of thinness persists. Societal and ethical considerations The availability of GLP-1 products through online channels raises ethical and public-health concerns. Regulatory authorities have warned that unapproved GLP-1 products sold online may be counterfeit, mislabeled, of uncertain quality, or associated with dosing errors and adverse events [ 13 ]. Even when products are obtained through online medical services rather than illicit vendors, there may be insufficient psychiatric screening, inadequate nutritional assessment, and limited follow-up. This case therefore has implications beyond the individual patient. It underscores the need for better education about the psychiatric risks of unsupervised weight-loss pharmacotherapy and for closer collaboration among psychiatrists, endocrinologists, and primary-care physicians. Limitations This case report has several limitations. First, disordered-eating behaviors were already present before tirzepatide initiation, and therefore causality cannot be definitively established. Second, detailed quantitative data on caloric intake, urine ketones, and serial acid-base measurements were limited. Third, the authenticity and storage conditions of the tirzepatide product obtained through online services could not be independently verified. Nevertheless, the temporal association between rapid weight loss, marked ketonemia, and subsequent psychiatric evaluation provides a clinically important illustration of the potential metabolic and psychiatric risks of unsupervised incretin use. Conclusions Unsupervised tirzepatide use obtained through online services can be associated with serious metabolic complications such as starvation ketosis and may unmask or exacerbate pre-existing eating-disorder pathology. Importantly, metabolic recovery may precede psychiatric recovery. Careful screening, longitudinal psychiatric follow-up, and interdisciplinary management are therefore essential when caring for patients with disordered-eating vulnerability who use incretin-based therapies. Declarations Ethics approval and consent to participate Ethical approval was not required for this case report in accordance with institutional policy. Consent for publication Written informed consent was obtained from the patient for publication of this case report and the accompanying table. Competing interests The authors declare that they have no competing interests. Funding No specific funding was received for this work. Author Contribution NF, KT, YK and YA were involved in clinical care, data collection, and manuscript preparation. All authors read and approved the final manuscript. Data Availability All data relevant to this case report are included in the article. References Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26–36. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989–1002. Bartel S, McElroy SL, Levangie D, Keshen A. Use of glucagon-like peptide-1 receptor agonists in eating disorder populations. Int J Eat Disord. 2024;57(2):286–93. Aoun L, Almardini S, Saliba F, Haddadin F, Mourad O, Jdaidani J, et al. GLP-1 receptor agonists: a novel pharmacotherapy for binge eating (binge eating disorder and bulimia nervosa)? A systematic review. J Clin Transl Endocrinol. 2024;35:100333. Martin CK, Carmichael OT, Carnell S, Considine RV, Kareken DA, Dydak U, et al. Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial. Nat Med. 2025;31(9):3141–50. Guerdjikova AI, Ward A, Ontiveros M, McElroy SL. Semaglutide misuse in atypical anorexia nervosa: a case report. J Clin Psychopharmacol. 2024;44(2):179–80. Guerdjikova AI, Dlugosz H, Wolterman R, McElroy SL. Relapse in anorexia nervosa associated with tirzepatide: a case report. J Clin Psychopharmacol. 2025;45(3):287–8. Mudd MK, Rado JT. Mental health effects of tirzepatide: a report of 2 patients. Prim Care Companion CNS Disord. 2025;27(4):25cr03931. Chen W, Cai P, Zou W, Fu Z. Psychiatric adverse events associated with GLP-1 receptor agonists: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database. Front Endocrinol (Lausanne). 2024;15:1330936. Kałas M, Stępniewska E, Gniedziejko M, Leszczyński-Czeczatka J, Siemiński M. Glucagon-like peptide-1 receptor agonists in the context of eating disorders: a promising therapeutic option or a double-edged sword? J Clin Med. 2025;14(9):3122. Garner DM, Olmsted MP, Bohr Y, Garfinkel PE. The eating attitudes test: psychometric features and clinical correlates. Psychol Med. 1982;12(4):871–8. Nohara N, Hiraide M, Horie T, Takakura S, Hata T, Sudo N, et al. The optimal cut-off score of the Eating Attitude Test-26 for screening eating disorders in Japan. Eat Weight Disord. 2024;29(1):42. Food US, Administration D. Mar. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss . Accessed 30 2026. Tables Table 1. Clinical time course of the patient Time point (relative to tirzepatide initiation) Body weight (kg) BMI (kg/m²) Tirzepatide dose Key clinical features and findings Age 18 years 56 21.3 None Dieting behaviors; reduced meal frequency; recurrent binge eating with self-induced vomiting Month 0 47 17.9 2.5 mg/week Self-administration of tirzepatide obtained through online services; no direct medical supervision Month 1 — — 5.0 mg/week Continued appetite suppression and progressive weight loss Month 2 41 15.6 5.0 mg/week Severe nausea, repeated bilious vomiting, presyncope Month 2 (emergency admission) — — 5.0 mg/week Diagnosed with starvation ketosis Month 2 (laboratory findings) — — — 3-hydroxybutyrate 2057 µmol/L; glucose 79 mg/dL; HbA1c 5.1%; Na 141 mmol/L; K 3.8 mmol/L; Cl 100 mmol/L; anion gap 16.9 mmol/L without K (20.5 mmol/L with K); venous pH 7.437; PCO₂ 36.4 mmHg; HCO₃⁻ 24.0 mmol/L; base excess 0.3 mmol/L; lactate 2.4 mmol/L; no SGLT2 inhibitor use; no habitual alcohol consumption Month 2 (discharge) — — Discontinued Symptoms improved after intravenous glucose infusion and nutritional refeeding Month 2-3 (psychiatric evaluation) 41 15.6 None Diagnosed with anorexia nervosa; EAT-26 = 22 Month 3 (early follow-up) 42 16.0 None 3-hydroxybutyrate 166 µmol/L (reference range, 0-74); EAT-26 = 14 Month 7 (later follow-up) 42 16.0 None 3-hydroxybutyrate 24 µmol/L (reference range, 0-74); EAT-26 = 16; drive for thinness persisted; ongoing psychiatric follow-up Abbreviations: BMI, body mass index; EAT-26, Eating Attitudes Test-26. Month 0 indicates tirzepatide initiation. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 29 Apr, 2026 Reviews received at journal 29 Apr, 2026 Reviews received at journal 29 Apr, 2026 Reviewers agreed at journal 16 Apr, 2026 Reviewers agreed at journal 14 Apr, 2026 Reviewers invited by journal 14 Apr, 2026 Editor assigned by journal 06 Apr, 2026 Submission checks completed at journal 06 Apr, 2026 First submitted to journal 01 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9289959","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":624559430,"identity":"91f21eaf-a5a6-481a-8854-5a93c875a86e","order_by":0,"name":"Norio Yasui-Furukori","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYBAC9gYGBkYg5uFnSGAGMYAgAUSw4dTCcwCqRbKBVC0MBgdQteAGPBK5zyRnVNyTMT6efNhwZptNND97AuOHHwx8ebi1pJtJbjhTzGN25lly4sa2tNyZPQ+YJXsY2IpxabGXSGOTfNiWwGN2I8f44MO2w7kbbiQwSAP9ktiA0xaoFuMZUC37byQw/yaoZSNQi4FEjjHQYUBbJBLY8NvC84zZcsaZBB4JoF8MZ5xLy51x5mGbZY8Bbr/wsKcx3uypSLDnb08+LNlTZpPbD2Tc+FFxDGeIoQJGcASCosfgWAJxWhj+wFk1xGoZBaNgFIyC4Q8ArZpX+YpmKxEAAAAASUVORK5CYII=","orcid":"","institution":"Dokkyo Medical University","correspondingAuthor":true,"prefix":"","firstName":"Norio","middleName":"","lastName":"Yasui-Furukori","suffix":""},{"id":624559431,"identity":"253bac3e-cda5-4acd-a7b5-0090ef0439b7","order_by":1,"name":"Kasumi Tasaki","email":"","orcid":"","institution":"Dokkyo Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kasumi","middleName":"","lastName":"Tasaki","suffix":""},{"id":624559432,"identity":"ec9385d1-9be6-4de7-94f7-538f277aa622","order_by":2,"name":"Yusuke Kaiga","email":"","orcid":"","institution":"Dokkyo Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yusuke","middleName":"","lastName":"Kaiga","suffix":""},{"id":624559433,"identity":"0fb205cf-7546-4d4d-97c9-edc47d55a2ef","order_by":3,"name":"Yoshimasa Aso","email":"","orcid":"","institution":"Dokkyo Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yoshimasa","middleName":"","lastName":"Aso","suffix":""}],"badges":[],"createdAt":"2026-04-01 09:43:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9289959/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9289959/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107706500,"identity":"1b117b0d-d4ec-40ba-afe4-1c62c314c911","added_by":"auto","created_at":"2026-04-24 09:18:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":181856,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9289959/v1/a644540f-b80c-426a-9edf-daa786123bff.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Starvation ketosis following self-administered tirzepatide obtained via online services in a young woman later diagnosed with anorexia nervosa: a case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GIP/GLP-1 receptor agonists have transformed the management of obesity and type 2 diabetes through potent appetite suppression, delayed gastric emptying, and marked weight reduction [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Tirzepatide, a dual GIP/GLP-1 receptor agonist, has demonstrated superior weight reduction compared with semaglutide in a head-to-head phase 3b trial in adults with obesity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlongside their expanding clinical use, access to incretin-based agents through online services has raised concerns about use without adequate longitudinal supervision. Emerging reviews suggest that GLP-1RAs may improve, maintain, or worsen eating-disorder symptoms depending on the clinical context, underscoring the need for caution in vulnerable individuals [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStarvation ketosis is a metabolic condition characterized by elevated ketone bodies resulting from prolonged caloric restriction, typically in the absence of hyperglycemia or severe acidemia. Although uncommon, it represents a clinically important complication of extreme weight loss. Here, we describe a case of starvation ketosis following unsupervised tirzepatide use, after which anorexia nervosa was clinically recognized.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eThe patient was a 21-year-old woman with no documented formal psychiatric or metabolic disorders. At the age of 18 years, her body weight was 56 kg. She had engaged in dieting behaviors, including reducing meal frequency from three to two meals per day, as well as recurrent binge eating followed by self-induced vomiting. Although these behaviors were not previously evaluated psychiatrically, her desire for further weight loss persisted. In mid-2025, seeking additional weight reduction, she obtained tirzepatide (Mounjaro\u0026reg;) through online medical services and initiated self-injection without direct medical supervision. The initial dose was 2.5 mg once weekly for approximately four weeks, after which the dose was increased to 5.0 mg once weekly. At the start of tirzepatide administration (Month 0), her body weight was 47 kg. Over the subsequent two months, her weight decreased to 41 kg at a height of 162 cm, corresponding to a reduction in body mass index (BMI) from 17.9 kg/m\u0026sup2; to 15.6 kg/m\u0026sup2;, representing an approximate 12.8% loss of body weight. Approximately two months after initiating tirzepatide, she developed severe nausea, repeated bilious vomiting, and presyncope with difficulty maintaining an upright posture, which led to emergency admission. Laboratory investigations at admission revealed a markedly elevated serum 3-hydroxybutyrate level of 2057 \u0026micro;mol/L, indicating significant ketonemia. Plasma glucose was 79 mg/dL, HbA1c was 5.1%, and there was no history of SGLT2 inhibitor use or habitual alcohol consumption. Serum electrolytes were as follows: sodium 141 mmol/L, potassium 3.8 mmol/L, and chloride 100 mmol/L. The anion gap was 16.9 mmol/L when calculated without potassium (20.5 mmol/L including potassium). Venous blood gas analysis demonstrated a pH of 7.437, partial pressure of carbon dioxide of 36.4 mmHg, bicarbonate of 24.0 mmol/L, and a base excess of 0.3 mmol/L, indicating the absence of clinically significant acidemia. Serum lactate was 2.4 mmol/L, excluding clinically relevant lactic acidosis. In the context of marked ketonemia, normoglycemia, mildly elevated anion gap, recent rapid weight loss, reduced oral intake, and no SGLT2 inhibitor exposure, she was diagnosed with starvation ketosis rather than diabetic ketoacidosis. Treatment consisted of intravenous glucose-containing fluids and electrolyte replacement, followed by gradual reintroduction of oral intake. Her gastrointestinal symptoms and general condition improved, and she was discharged after several days of inpatient care. The clinical course is summarized in Table\u0026nbsp;1. Shortly after discharge, psychiatric evaluation was performed because of persistent anxiety related to eating and an intense fear of weight gain. At that time, her body weight remained 41 kg (BMI 15.6 kg/m\u0026sup2;). Psychological assessment revealed a pronounced drive for thinness, body-image distortion, and restrictive eating behavior. Based on DSM-5 criteria, she was diagnosed with anorexia nervosa. The Eating Attitudes Test-26 (EAT-26) score was 22, exceeding the conventional cut-off score of 20 suggestive of an eating disorder. Psychoeducation and nutritional counseling were initiated, and regular psychiatric follow-up was arranged. At early outpatient follow-up, her body weight had increased to 42 kg. Serum 3-hydroxybutyrate remained elevated at 166 \u0026micro;mol/L (reference range, 0\u0026ndash;74 \u0026micro;mol/L), while the EAT-26 score had decreased to 14. At a later outpatient reassessment several months later, her body weight remained 42 kg (BMI 16.0 kg/m\u0026sup2;). Serum 3-hydroxybutyrate had normalized to 24 \u0026micro;mol/L, whereas the EAT-26 score was 16. Although ketonemia had resolved, her drive for thinness persisted. She continues to receive outpatient psychiatric follow-up.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case illustrates a clinically significant intersection of metabolic and psychiatric pathology: starvation ketosis temporally associated with unsupervised tirzepatide use in a young woman later diagnosed with anorexia nervosa. The case is notable not only because of the metabolic complication itself, but also because metabolic improvement did not parallel full psychiatric improvement.\u003c/p\u003e\n\u003ch3\u003eGLP-1/GIP receptor agonists and eating behavior\u003c/h3\u003e\n\u003cp\u003eTirzepatide exerts its effects through combined GIP and GLP-1 receptor agonism, producing marked appetite suppression and changes in ingestive behavior [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Although incretin-based therapies are effective for obesity treatment, reviews of GLP-1 receptor agonists in eating-disorder populations emphasize that these agents may improve, maintain, or worsen eating-disorder symptoms depending on patient characteristics and treatment context [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This bidirectional potential is especially relevant in patients with pre-existing disordered-eating behaviors or strong weight-related psychopathology.\u003c/p\u003e \u003cp\u003eRecent case reports describe semaglutide misuse in atypical anorexia nervosa and relapse of anorexia nervosa associated with tirzepatide [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Pharmacovigilance data have also suggested signals for psychiatric adverse events with GLP-1 receptor agonists, although such data do not establish causality [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Taken together, these findings support the view that incretin-based therapies should not be considered purely metabolic agents, but rather drugs with potential psychobehavioral effects in susceptible individuals.\u003c/p\u003e\n\u003ch3\u003eStarvation ketosis without clinically significant acidemia\u003c/h3\u003e\n\u003cp\u003eThe present case is notable for marked ketonemia (serum 3-hydroxybutyrate 2057 \u0026micro;mol/L) without clinically significant acidemia. The diagnosis of starvation ketosis was supported by normoglycemia (79 mg/dL), normal HbA1c (5.1%), absence of SGLT2 inhibitor exposure or habitual alcohol consumption, and a mildly elevated anion gap, in addition to recent rapid weight loss and reduced oral intake. Starvation ketosis arises from glycogen depletion and enhanced fatty-acid oxidation during prolonged caloric restriction, typically with normal or low blood glucose levels. Unlike diabetic ketoacidosis, the acid-base disturbance may be mild or absent, particularly when assessment occurs early or after partial compensation.\u003c/p\u003e \u003cp\u003eIn this patient, the combination of substantial recent weight loss, reduced oral intake, gastrointestinal symptoms, normoglycemia, and marked ketonemia supported starvation ketosis rather than diabetic ketoacidosis. Clinicians should therefore consider measuring serum ketones in patients receiving incretin-based therapies who present with nausea, vomiting, malaise, or presyncope, even in the absence of overt acidemia.\u003c/p\u003e\n\u003ch3\u003ePsychiatric implications\u003c/h3\u003e\n\u003cp\u003eA central psychiatric implication of this case is that tirzepatide-associated appetite suppression and rapid weight loss likely interacted with pre-existing dieting behavior and may have contributed to the clinical recognition or worsening of eating-disorder psychopathology rather than unequivocal de novo onset of anorexia nervosa. The patient had engaged in dieting and binge-purge behavior before tirzepatide initiation, suggesting pre-existing vulnerability. However, the temporal association between self-administered tirzepatide, rapid weight loss, medical decompensation, and subsequent psychiatric diagnosis is clinically meaningful.\u003c/p\u003e \u003cp\u003eGLP-1 signaling influences reward-related and motivational pathways, and pharmacologically induced weight loss may function as a strong reinforcer for restrictive eating in vulnerable individuals [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In this context, the medication may have amplified pre-existing cognitive and behavioral tendencies centered on thinness, control, and fear of weight gain.\u003c/p\u003e\n\u003ch3\u003eInterpretation of EAT-26 scores during follow-up\u003c/h3\u003e\n\u003cp\u003eThe longitudinal EAT-26 findings in this case warrant cautious interpretation. Although the score decreased from 22 at initial psychiatric evaluation to 14 at early follow-up, and was 16 at later follow-up, these values should not be interpreted as evidence of remission. The EAT-26 was originally developed as a screening and case-finding instrument rather than a diagnostic tool [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The conventional threshold of 20 is intended to identify individuals who require further professional evaluation, but scores below 20 do not exclude clinically significant eating-disorder psychopathology. Moreover, a recent case-control study in Japan suggested that an optimal cut-off score for DSM-5 eating disorders may be lower, at 17 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the present case, therefore, the decline in EAT-26 scores likely reflects partial improvement in self-reported symptoms rather than full psychiatric recovery.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDivergence between metabolic and psychiatric recovery\u003c/h2\u003e \u003cp\u003eA particularly important feature of this case is that normalization of ketone levels did not coincide with full improvement in eating-disorder psychopathology. At early outpatient follow-up, serum 3-hydroxybutyrate remained elevated at 166 \u0026micro;mol/L despite an increase in body weight to 42 kg and a reduction in EAT-26 score from 22 to 14. At later follow-up, serum 3-hydroxybutyrate had normalized to 24 \u0026micro;mol/L, but her body weight remained 42 kg and her drive for thinness persisted; the EAT-26 score also remained elevated at 16. These findings suggest that metabolic stabilization after starvation ketosis does not necessarily indicate remission of the underlying eating disorder.\u003c/p\u003e \u003cp\u003eClinicians should therefore interpret improvement in biochemical parameters or questionnaire scores cautiously and continue longitudinal psychiatric assessment, particularly in patients whose weight restoration remains limited and whose overvaluation of thinness persists.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSocietal and ethical considerations\u003c/h3\u003e\n\u003cp\u003eThe availability of GLP-1 products through online channels raises ethical and public-health concerns. Regulatory authorities have warned that unapproved GLP-1 products sold online may be counterfeit, mislabeled, of uncertain quality, or associated with dosing errors and adverse events [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Even when products are obtained through online medical services rather than illicit vendors, there may be insufficient psychiatric screening, inadequate nutritional assessment, and limited follow-up.\u003c/p\u003e \u003cp\u003eThis case therefore has implications beyond the individual patient. It underscores the need for better education about the psychiatric risks of unsupervised weight-loss pharmacotherapy and for closer collaboration among psychiatrists, endocrinologists, and primary-care physicians.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis case report has several limitations. First, disordered-eating behaviors were already present before tirzepatide initiation, and therefore causality cannot be definitively established. Second, detailed quantitative data on caloric intake, urine ketones, and serial acid-base measurements were limited. Third, the authenticity and storage conditions of the tirzepatide product obtained through online services could not be independently verified. Nevertheless, the temporal association between rapid weight loss, marked ketonemia, and subsequent psychiatric evaluation provides a clinically important illustration of the potential metabolic and psychiatric risks of unsupervised incretin use.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eUnsupervised tirzepatide use obtained through online services can be associated with serious metabolic complications such as starvation ketosis and may unmask or exacerbate pre-existing eating-disorder pathology. Importantly, metabolic recovery may precede psychiatric recovery. Careful screening, longitudinal psychiatric follow-up, and interdisciplinary management are therefore essential when caring for patients with disordered-eating vulnerability who use incretin-based therapies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e \u003cp\u003eEthical approval was not required for this case report in accordance with institutional policy.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003e Written informed consent was obtained from the patient for publication of this case report and the accompanying table.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo specific funding was received for this work.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eNF, KT, YK and YA were involved in clinical care, data collection, and manuscript preparation. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data relevant to this case report are included in the article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, et al. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989\u0026ndash;1002.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBartel S, McElroy SL, Levangie D, Keshen A. Use of glucagon-like peptide-1 receptor agonists in eating disorder populations. Int J Eat Disord. 2024;57(2):286\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAoun L, Almardini S, Saliba F, Haddadin F, Mourad O, Jdaidani J, et al. GLP-1 receptor agonists: a novel pharmacotherapy for binge eating (binge eating disorder and bulimia nervosa)? A systematic review. J Clin Transl Endocrinol. 2024;35:100333.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartin CK, Carmichael OT, Carnell S, Considine RV, Kareken DA, Dydak U, et al. Tirzepatide on ingestive behavior in adults with overweight or obesity: a randomized 6-week phase 1 trial. Nat Med. 2025;31(9):3141\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuerdjikova AI, Ward A, Ontiveros M, McElroy SL. Semaglutide misuse in atypical anorexia nervosa: a case report. J Clin Psychopharmacol. 2024;44(2):179\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuerdjikova AI, Dlugosz H, Wolterman R, McElroy SL. Relapse in anorexia nervosa associated with tirzepatide: a case report. J Clin Psychopharmacol. 2025;45(3):287\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMudd MK, Rado JT. Mental health effects of tirzepatide: a report of 2 patients. Prim Care Companion CNS Disord. 2025;27(4):25cr03931.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen W, Cai P, Zou W, Fu Z. Psychiatric adverse events associated with GLP-1 receptor agonists: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database. Front Endocrinol (Lausanne). 2024;15:1330936.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKałas M, Stępniewska E, Gniedziejko M, Leszczyński-Czeczatka J, Siemiński M. Glucagon-like peptide-1 receptor agonists in the context of eating disorders: a promising therapeutic option or a double-edged sword? J Clin Med. 2025;14(9):3122.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarner DM, Olmsted MP, Bohr Y, Garfinkel PE. The eating attitudes test: psychometric features and clinical correlates. Psychol Med. 1982;12(4):871\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNohara N, Hiraide M, Horie T, Takakura S, Hata T, Sudo N, et al. The optimal cut-off score of the Eating Attitude Test-26 for screening eating disorders in Japan. Eat Weight Disord. 2024;29(1):42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFood US, Administration D. Mar. FDA\u0026rsquo;s concerns with unapproved GLP-1 drugs used for weight loss. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss\u003c/span\u003e\u003cspan address=\"https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 30 2026.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Clinical time course of the patient\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTime point (relative to tirzepatide initiation)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eBody weight (kg)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eBMI (kg/m²)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTirzepatide dose\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eKey clinical features and findings\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eAge 18 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e21.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDieting behaviors; reduced meal frequency; recurrent binge eating with self-induced vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonth 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.5 mg/week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSelf-administration of tirzepatide obtained through online services; no direct medical supervision\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonth 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.0 mg/week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eContinued appetite suppression and progressive weight loss\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonth 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.0 mg/week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSevere nausea, repeated bilious vomiting, presyncope\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonth 2 (emergency admission)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.0 mg/week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDiagnosed with starvation ketosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonth 2 (laboratory findings)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3-hydroxybutyrate 2057 µmol/L; glucose 79 mg/dL; HbA1c 5.1%; Na 141 mmol/L; K 3.8 mmol/L; Cl 100 mmol/L; anion gap 16.9 mmol/L without K (20.5 mmol/L with K); venous pH 7.437; PCO₂ 36.4 mmHg; HCO₃⁻ 24.0 mmol/L; base excess 0.3 mmol/L; lactate 2.4 mmol/L; no SGLT2 inhibitor use; no habitual alcohol consumption\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonth 2 (discharge)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e—\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDiscontinued\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eSymptoms improved after intravenous glucose infusion and nutritional refeeding\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonth 2-3 (psychiatric evaluation)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDiagnosed with anorexia nervosa; EAT-26 = 22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonth 3 (early follow-up)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3-hydroxybutyrate 166 µmol/L (reference range, 0-74); EAT-26 = 14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eMonth 7 (later follow-up)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3-hydroxybutyrate 24 µmol/L (reference range, 0-74); EAT-26 = 16; drive for thinness persisted; ongoing psychiatric follow-up\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: BMI, body mass index; EAT-26, Eating Attitudes Test-26. Month 0 indicates tirzepatide initiation.\u003c/em\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-eating-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joed","sideBox":"Learn more about [Journal of Eating Disorders](http://jeatdisord.biomedcentral.com)","snPcode":"40337","submissionUrl":"https://submission.nature.com/new-submission/40337/3","title":"Journal of Eating Disorders","twitterHandle":"@JEatDisord","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"tirzepatide, starvation ketosis, anorexia nervosa, GLP-1 receptor agonist, self-medication, eating disorder","lastPublishedDoi":"10.21203/rs.3.rs-9289959/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9289959/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, induces potent appetite suppression and substantial weight loss. Increasing access to incretin-based therapies through online services has raised concerns regarding metabolic and psychiatric complications, particularly in vulnerable individuals. We report a case of starvation ketosis associated with self-administered tirzepatide, followed by the clinical recognition of anorexia nervosa.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eA 21-year-old woman with no prior formal psychiatric or metabolic diagnoses had a history of dieting behaviors and intermittent binge-purge episodes. Seeking further weight loss, she obtained tirzepatide through online medical services and self-administered 2.5 mg weekly for approximately four weeks, followed by 5.0 mg weekly for another month, without direct medical supervision. Her body weight decreased from 47 kg to 41 kg (BMI 17.9 to 15.6 kg/m\u0026sup2;). Approximately two months after initiation, she developed severe nausea, bilious vomiting, and presyncope, requiring emergency admission. Laboratory evaluation revealed marked ketonemia (serum 3-hydroxybutyrate 2057 \u0026micro;mol/L), normoglycemia (glucose 79 mg/dL), mildly elevated anion gap, normal HbA1c (5.1%), and no clinically significant acidemia. She had no history of SGLT2 inhibitor use or habitual alcohol consumption. She was diagnosed with starvation ketosis and improved with intravenous glucose infusion and nutritional support. Shortly after discharge, psychiatric evaluation led to a diagnosis of anorexia nervosa. At early follow-up, body weight had increased to 42 kg, the Eating Attitudes Test-26 (EAT-26) score decreased to 14, but serum 3-hydroxybutyrate remained elevated at 166 \u0026micro;mol/L. At later outpatient reassessment several months later, body weight remained 42 kg, serum 3-hydroxybutyrate had normalized to 24 \u0026micro;mol/L, and the EAT-26 score was 16; however, her drive for thinness persisted.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis case highlights that unsupervised tirzepatide use may be associated with starvation ketosis and the clinical recognition or exacerbation of eating-disorder psychopathology. Metabolic recovery did not parallel full improvement in eating-disorder symptoms, underscoring the need for careful screening, longitudinal psychiatric follow-up, and interdisciplinary management when incretin-based therapies are used.\u003c/p\u003e","manuscriptTitle":"Starvation ketosis following self-administered tirzepatide obtained via online services in a young woman later diagnosed with anorexia nervosa: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-22 13:18:06","doi":"10.21203/rs.3.rs-9289959/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-29T19:50:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-29T19:22:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-29T18:36:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"267173877576074428742686941015986050463","date":"2026-04-16T21:49:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"158327086660047071743186793831316020080","date":"2026-04-14T23:57:54+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-14T23:07:56+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-06T11:04:33+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-06T11:04:27+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Eating Disorders","date":"2026-04-01T09:26:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-eating-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joed","sideBox":"Learn more about [Journal of Eating Disorders](http://jeatdisord.biomedcentral.com)","snPcode":"40337","submissionUrl":"https://submission.nature.com/new-submission/40337/3","title":"Journal of Eating Disorders","twitterHandle":"@JEatDisord","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b181775f-50e8-4599-890a-34c878ab1d57","owner":[],"postedDate":"April 22nd, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-04-29T19:50:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-29T19:22:58+00:00","index":13,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-29T18:36:26+00:00","index":12,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T11:54:14+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-22 13:18:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9289959","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9289959","identity":"rs-9289959","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}