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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.
OVERVIEW
Introduction
Tirzepatide is an agonist of the receptors of two insulin sensitizing polypeptides, GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide 1), that is used as therapy of type 2 diabetes, obstructive sleep apnea, and obesity. Tirzepatide has been linked to minimal instances of elevations in serum aminotransferase levels during therapy and rare episodes of clinically apparent liver injury.
Background
Tirzepatide (tir zep’ a tide) is a 39 amino acid modified peptide similar in structure to the glucose-dependent insulinotropic polypeptide (GIP) that acts as an agonist to both the GIP receptor and the glucagon-like peptide 1 (GLP-1) receptor. Tirzepatide therapy increases insulin secretion, decreases glucagon secretion and delays gastric emptying. The result is a decrease in both fasting and postprandial glucose concentrations and an increase in insulin sensitivity. Tirzepatide also results in a decrease in food intake and reduced body weight. In multiple, preregistration clinical trials, tirzepatide therapy improved glycemic control and lowered HgA1c levels in patients with type 2 diabetes. It also resulted in weight loss of 7 to 11 kilograms after 40 to 52 weeks of treatment and to 16 to 24 kilograms after 72 weeks. Tirzepatide was approved for use as an adjunct to diet and exercise in type 2 diabetes in 2022 and for obesity in 2024. It is under active evaluation as therapy for nonalcoholic steatohepatitis. Tirzepatide is available as a solution in single use vials or autoinjectors as 2.5, 5, 7.5, 10, 12.5 and 15 mg (in 0.5 mL) under the brand name Mounjaro for therapy of diabetes and Zepbound for obesity. The recommended starting dosage is 2.5 mg subcutaneously once weekly, with gradual dose escalation in increments of 2.5 mg every 4 weeks to a maintenance dose of 5, 10 or 15 mg weekly. Common adverse events include injection site reactions and nonspecific gastrointestinal complaints of nausea, vomiting, diarrhea, constipation, decreased appetite, dyspepsia, and abdominal discomfort. Less common but potentially severe adverse events include hypersensitivity reactions, pancreatitis, gallstones and cholecystitis, hypoglycemia (when used with insulin or insulin secretagogues), suicidal ideation and behavior, aspiration during general anesthesia, and worsening of preexisting severe renal and gastrointestinal diseases. Tirzepatide has a boxed warning for risk of thyroid C-cell tumors and is contraindicated in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2).
Hepatotoxicity
In preregistration clinical trials, serum aminotransferase elevations of greater than 3 times the upper limit of normal (ULN) arose in less than 1% of patients during therapy with tirzepatide and similar rates occurred in placebo recipients and in comparator arm groups. In studies of more than 5,000 patients, there were no reports of severe liver test abnormalities or clinically apparent liver injury attributable to tirzepatide. Indeed, tirzepatide therapy is often associated with improvements in serum aminotransferase levels probably as a result of weight loss. On the other hand, tirzepatide has been associated with a slightly higher rate of acute gallbladder disease (cholelithiasis, biliary cholic and cholecystectomy) reported in 0.6% of treated patients vs none of placebo-treated patients. Gallbladder conditions are mentioned in the warning section of the product label for tirzepatide. Subsequent to its approval and more widespread use, there have been isolated case reports of acute liver injury in patients taking tirzepatide. Reported cases have been marked by a latency of 1 to 4 months, hepatocellular pattern of liver enzyme elevations, mild jaundice, and a benign, self-limited course. One patient had worsening of liver enzyme elevations on restarting, and others have later tolerated switching to a GLP-1 agonist without recurrence of liver injury. The risk for clinically apparent liver injury with long-term tirzepatide use is unknown but is likely to be very rare.
Likelihood score: C (probable rare cause of clinically apparent liver injury).
Mechanism of Injury
The mechanism by which tirzepatide might cause liver injury is unknown. It is a modified polypeptide and is metabolized to individual amino acids in multiple tissues and cell types including the liver. Because it causes weight loss, it can be accompanied by improvements in serum aminotransferase levels in patients with preexisting nonalcoholic fatty liver. The increased risk of acute gallbladder disease such as cholecystitis is probably related to the rapid weight loss that occurs with treatment.
Outcome and Management
The product label for tirzepatide does not recommend routine monitoring of liver tests during therapy. Because of the reports of acute liver injury with its use, however, tirzepatide should be at least temporarily discontinued if serum aminotransferase levels are found to rise above 5 times the ULN or for any ALT elevations accompanied by symptoms of liver disease or jaundice. Patients with intolerance to tirzepatide may be able to tolerate GLP-1 agonists such as semaglutide or liraglutide.
Drug Class: Antidiabetic Agents, Weight Loss Agents
Other Related Drugs: Incretin-Based Drugs, Glucagon-Like Peptide-1 (GLP-1) Analogues, Liraglutide, Semaglutide
CASE REPORT
Case 1. Acute liver injury attributed to tirzepatide.(1)
A 65 year old white male with type 2 diabetes, on metformin for 4 years and empagliflozin for 2 years, was started on weekly subcutaneous (sc) injections of tirzepatide to improve his glycemic control. Six weeks later he developed fever, abdominal pain, and nausea followed by jaundice. On presentation, he had abdominal tenderness over the liver and had scleral icterus. He had no history of hepatitis or jaundice, did not drink alcohol, and had no risk factors for viral hepatitis. His other medications included rosuvastatin for hypercholesterolemia and ramipril and hydrochlorothiazide for hypertension (all of which he had taken for at least 10 years). Blood tests showed a total bilirubin of 5.8 mg/dL, ALT 1093 U/L, AST 629 U/L, and alkaline phosphatase 176 U/L (R = 17.9). The INR was 1.2 and albumin 4.4 g/dL. Tirzepatide, metformin, empagliflozin, and rosuvastatin were discontinued, and he was admitted for monitoring and management. Tests for hepatitis A, B, and C (including HCV RNA) were negative as were routine autoantibodies (ANA, SMA, AMA). Liver ultrasound and computerized tomography (CT) were normal. Abdominal MRI showed abnormal inflammatory enhancement in the liver parenchyma and sludge within the gallbladder without biliary dilatation. Serial liver tests demonstrated a rise in bilirubin to 7.5 mg/dL accompanied by rapid decreases in serum aminotransferase levels and increases in alkaline phosphatase levels (Table). The changes in serum enzymes resulted in cholestatic R values within 4 days of onset. A liver biopsy showed swollen injured hepatocytes around the central vein without steatosis or lobular inflammation, mild canaclicular cholestasis, and periportal bile ductural reaction. He was discharged on ramipril, hydrochlorothiazide, insulin and fish oil. He did well and was asymptomatic and had normal liver tests in follow up at 4 and 7 months after onset, but had gained 20 pounds after stopping tirzepatide and starting insulin.
Key Points
| Medication: | Tirzepatide (2 mg sc weekly) |
|---|---|
| Pattern: | Initially hepatocellular (R=17.9), then cholestatic (R< 2.0) |
| Severity: | 3+ (jaundice, hospitalization) |
| Latency: | 6 weeks |
| Recovery: | Complete within 1-2 months |
| Other medications: | Rosuvastatin, ramipril, hydrochlorothiazide, metformin, empagliflozin, multivitamins with calcium and iron, aspirin. |
Laboratory Values
| Time After Starting | Time After Stopping | ALT (U/L) | Alk P (U/L) | Bilirubin (mg/dL) | Other |
|---|---|---|---|---|---|
| 6 weeks | 0 | 1093 | 176 | 5.8 | R = 17.9, Admission |
| 1 | 744 | 165 | 5.8 | US & CT Scan normal | |
| 2 | 427 | 210 | 5.5 | R = 5.8, INR 1.0 | |
| 3 | 298 | 300 | 6.4 | R = 2.8 | |
| 4 | 227 | 369 | 7.5 | R = 1.8, MRI | |
| 6 | 298 | 466 | 4.3 | R = 1.5, INR 1.0 | |
| 8 | 239 | 360 | 2.1 | ||
| 9 | 246 | 389 | 2.3 | Liver biopsy | |
| 10 | 210 | 365 | 1.9 | R = 1.4, Discharged | |
| 2 months | 13 | 122 | 299 | 1.5 | |
| 23 | 48 | 166 | 1.0 | ||
| 3 months | 5 weeks | 39 | 117 | 0.7 | |
| 5 months | 4 months | 23 | 80 | 0.1 | Normal values |
| 8 months | 7 months | 23 | 93 | 0.6 | Normal, INR 1.0 |
| Upper Limits of Normal | 45 | 125 | 1.2 | ||
Comment
A middle aged man with diabetes, hypertension, and hypercholesterolemia, developed jaundice 6 weeks after starting weekly subcutaneous injections of tirzepatide to improve glycemic control. Tirzepatide was promptly discontinued but so were rosuvastatin and empagliflozin, important agents that he had been receiving for years without problems. The initial presentation was with acute hepatocellular injury. The liver injury improved with only mild increases in serum bilirubin for 4 days accompanied by a rapid drop in aminotransferase but concomitant rise in alkaline phosphatase levels. Other causes of liver disease were excluded, but imaging demonstrated the presence of biliary sludge. Actually, the clinical features were compatible with acute biliary obstruction from a common bile duct gallstone that was then rapidly passed. On expert review, this case was adjudicated as probable drug-induced liver injury from tirzepatide. Acute and transient biliary obstruction from gallstones was judged to be only possibly the cause of the liver injury. Rechallenge with tirzepatide might have been tried if it had been considered necessary. Certainly, rechallenge with rosuvastatin or empagliflozin would have been warranted if needed and a different GLP-1 tried with careful monitoring.
PRODUCT INFORMATION
REPRESENTATIVE TRADE NAMES
Tirzepatide – Mounjaro®, Zepbound®
DRUG CLASS
Antidiabetic Agents, Weight Loss Agents
Product labeling at DailyMed, National Library of Medicine, NIH
CHEMICAL FORMULA AND STRUCTURE
| DRUG | CAS REGISTRY NUMBER | MOLECULAR FORMULA | STRUCTURE |
|---|---|---|---|
| Tirzepatide | 2023788-19-2 | Protein | Polypeptide |
ANNOTATED BIBLIOGRAPHY
References updated: 27 June 2025
- Abbreviations used: GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; HbA1c, hemoglobin A1c.
- Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999.(Textbook of hepatotoxicity published in 1999; before the availability of tirzepatide).
- De Marzio DH, Navarro VJ. Antidiabetic drugs. Hepatotoxicity of cardiovascular and antidiabetic drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2011, pp. 528-30.(Review of hepatotoxicity of antidiabetic drugs; mentions that there have been no published reports of hepatotoxicity of the GLP-1 analogues, tirzepatide is not discussed).
- Powers AC, D'Alessio D. Endocrine pancreas and pharmacotherapy of diabetes mellitus and hypoglycemia. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 863-86.(Textbook of pharmacology and therapeutics; discusses glucagon-like peptide-1 and the incretin pathway and agents that act on this pathway, but does not discuss tirzepatide).
- FDA. https://www
.accessdata .fda.gov/drugsatfda_docs /nda/2022/215866Orig1s000MedR.pdf (FDA website with multidisciplinary review of safety and efficacy of tirzepatide [Mounjaro, for type 2 diabetes] mentions that marked aminotransferase elevations were uncommon and there were no severe hepatic adverse events in preregistration controlled trials, but that gallbladder disease arose in some treated patients [0.6%] but not in controls [none]). - FDA. https://www
.accessdata .fda.gov/drugsatfda_docs /nda/2024/217806Orig1s000MedR.pdf (FDA website with multidisciplinary review of safety and efficacy of tirzepatide [Zepbound, for weight loss] mentions that serum aminotransferase levels typically decrease more with tirzepatide than placebo [-22% vs -3%] and that de novo elevations of ALT are uncommon therapy severe acute gallbladder disease was more common with tirzepatide than placebo treatment [0.4% vs none] but that it was probably due to weight loss rather than intrinsic toxicity. elevations were uncommon and there were no severe hepatic adverse events in preregistration controlled trials, but that gallbladder disease arose in some treated patients [0.6%] but not in controls [none]). - Kern E, VanWagner LB, Yang GY, Rinella ME. Liraglutide-induced autoimmune hepatitis. JAMA Intern Med. 2014;174:984-7.. [PMC free article: PMC4423594] [PubMed: 24733687](Young woman with diabetes and vitiligo developed an acute hepatitis 4 months after starting liraglutide [bilirubin 9.1 mg/dL, ALT 1123 U/L, AST 991 U/L, Alk P 90 U/L, ANA “not significantly elevated] which worsened despite stopping liraglutide but responded to corticosteroid therapy that was continued long-term).
- Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, Urva S, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018;392(10160):2180-2193. [PubMed: 30293770](Among 316 patients with type 2 diabetes treated with once weekly tirzepatide [1,5,10 and 1 5 mg], dulaglutide [1.5 mg] or placebo for 26 weeks, decreases in HbA1c levels and body weight occurred in a dose-dependent pattern with tirzepatide, and adverse events included gastrointestinal complaints and injection site reactions while cholecystitis occurred in 1 and pancreatitis in 2 of the 211 tirzepatide treated patients).
- Patel AV, Jotwani PM, Lee TP. Drug-induced liver injury due to dulaglutide use. Am J Ther. 2019;26:e620-e622.. [PubMed: 30870146](64 year old African American man developed jaundice 2 months after starting dulaglutide for diabetes [bilirubin 3.6 mg/dL, ALT 191 U/L, AST 141 U/L, Alk P 301 U/L, INR 1.0] with HCV RNA in serum [1.4 million IU/mL] resolving over the next 4 to 5 months and no follow up of HCV status).
- Hartman ML, Sanyal AJ, Loomba R, Wilson JM, Nikooienejad A, Bray R, Karanikas CA, et al. Effects of novel dual GIP and GLP-1 receptor agonist tirzepatide on biomarkers of nonalcoholic steatohepatitis in patients with type 2 diabetes. Diabetes Care. 2020; 43:1352-1355. [PMC free article: PMC7245348] [PubMed: 32291277](Reanalysis of a controlled trial in 316 patients with type 2 diabetes [Frias 2018], found a decrease in mean ALT levels and increase in adiponectin levels in patients treated with higher doses of tirzepatide [5, 10 and 15 mg], but not with the lowest dose [1 mg] or with dulaglutide or placebo for 26 weeks).
- Yanovski SZ, Yanovski JA. Progress in pharmacotherapy for obesity. JAMA. 2021;326:129-130. [PMC free article: PMC8277731] [PubMed: 34160571](Brief review of the currently approved drugs for weight loss including the promising two new GLP-1 agonists, liraglutide and semaglutide, and tirzepatide which is in phase III trials in patients with obesity without diabetes).
- Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, et al.; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503-515. [PubMed: 34170647](Among 1879 patients with diabetes treated with tirzepatide [5, 10 or 15 mg] or semaglutide [1 mg] once weekly for 40 weeks, tirzepatide resulted in greater improvement in HbA1c levels and greater decrease in body weight [-7.6 to -11.2 kg vs -5.7 kg], while adverse event rates were similar, except for cholecystitis which arose in 12 of 1409 patients on tirzepatide vs no patients on semaglutide [0.9% vs 0%]; no mention of ALT elevations, mean levels decreased by 22% to 30%).
- Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, Mao H, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021; 398(10295):143-155. [PubMed: 34186022](Among 478 diabetic patients with in adequate control treated with tirzepatide [5, 10, or 15 mg] or placebo once weekly for 40 weeks, HbA1c and fasting serum glucose levels improved and weight decreased by 7 to 9.5 kg while adverse events include nausea, diarrhea, constipation, dyspepsia, decreased appetite, and injection site reactions [2%-3%], while no patient developed pancreatitis and only 1 cholecystitis; no mention of ALT elevation or hepatoxicity).
- Ludvik B, Giorgino F, Jódar E, Frias JP, Fernández Landó L, Brown K, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021; 398(10300):583-598. [PubMed: 34370970](Among 1444 patients with type 2 diabetes on metformin treated with once weekly tirzepatide [5, 10 or 15 mg] or daily insulin, tirzepatide was associated with greater decreases in HbA1c levels and body weight [-7.5 to -12.9 kg vs +2.3 kg] while gallbladder events were recorded in 4 [0.4%] on tirzepatide, but none on insulin; no mention of ALT elevations or hepatotoxicity).
- Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, Aizenberg D, et al.; SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021; 398(10313): 1811-1824. [PubMed: 34672967](Among 2002 patients with poorly controlled type 2 diabetes treated with weekly injections of tirzepatide [5, 10 or 15 mg] or daily insulin glargine [titrated doses], HbA1c and fasting glucose levels improved more with tirzepatide as did weight loss [-7.1 to -13.5 kg vs +2 kg] while adverse event rates were similar except for diarrhea, nausea, vomiting, dyspepsia, constipation and decreased appetite, which were more common with tirzepatide but decreased over time; pancreatitis and cholecystitis occurred in less than 1% in all groups; no mention of ALT levels or hepatotoxicity).
- Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, Rodríguez Á. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022; 327(6):534-545. [PMC free article: PMC8826179] [PubMed: 35133415](Among 475 patients with type 2 diabetes and inadequate glycemic control despite insulin therapy treated with tirzepatide [5, 10 or 15 mg] or placebo weekly for 40 weeks, HbA1c and fasting glucose levels decreased more with tirzepatide as did body weight while adverse events more frequent with tirzepatide included nausea, vomiting, diarrhea, constipation, dyspepsia, decreased appetite; no patient developed pancreatitis and only one cholelithiasis; no mention of ALT elevations or hepatotoxicity).
- Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, et al. Structural determinants of dual incretin receptor agonism by tirzepatide. Proc Natl Acad Sci U S A. 2022;119: e2116506119. [PMC free article: PMC9060465] [PubMed: 35333651](Cryogenic electron microscopy determination of structure and binding of tirzepatide to the GIP- and GLP-1 receptors).
- Drugs and devices for weight management. Med Lett Drugs Ther 2022;64:81-88. [PubMed: 35650672](Concise review of weight loss agents in current use in the US mentions that tirzepatide [an investigational agent] in doses of 5, 10 and 15 mg once weekly for 72 weeks resulted in weight loss of -16 to -24 kg [compared to +2 kg in placebo controls] in overweight and obese adults without diabetes).
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387;1434-1435. [PubMed: 36239655](Among 2539 obese or overweight non-diabetic adults treated with tirzepatide [5, 10 or 15 mg] or placebo once weekly for 72 weeks, weight loss was greater with tirzepatide [-16 to -24 kg] than placebo [-3 kg] and adverse events attributed to tirzepatide included nausea, vomiting, diarrhea, constipation and injection site reactions; pancreatitis occurred in 0.2% vs 0.2%, gallbladder disease in 1.2% vs 0.8%, and mean ALT levels decreased by 26% to 30% vs 13%; no mention of ALT elevations).
- Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, et al.; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503-515.. [PubMed: 34170647](Among 1879 patients with diabetes treated with tirzepatide [3 doses] or semaglutide for 40 weeks, mean HbA1c levels improved more with tirzepatide [-2.0% to -2.3%) than semaglutide [-1.9%] while adverse event rates were similar and serum ALT levels improved in both groups [-22% to -30% vs -22%]; no mention of hepatic adverse events.
- Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E, Yoneda M, et al; SYNERGY-NASH Investigators. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N Engl J Med. 2024;391:299-310.. [PubMed: 38856224](Among 190 adults with NASH treated with subcutaneous tirzepatide (3 doses) or placebo weekly for 52 weeks, resolution of NASH histologically was more frequent with tirzepatide [44% to 62% vs 10%], and adverse event rates were similar including severe events [6% in both] and “there was no evidence of drug-induced liver injury”).
- Fontana RJ, Choi EK, Kaganove J, Dodson A. First report of tirzepatide hepatotoxicity with jaundice. Clin Gastroenterol Hepatol. 2024;22:2538-2539.. [PubMed: 38964597](64 year old man with 4-year history of diabetes developed nausea, abdominal pain, and jaundice 6 weeks after starting tirzepatide [2.5 mg weekly] for glucose control [bilirubin 5.8 mg/dL, ALT 1093 U/L, AST 629 U/L, Alk P 176 U/L, bilirubin 7.3 mg/dL, INR 1.3] with resolution within 6 weeks of stopping).
- Abdullah I, El-Ghousain H, Alenezi M. Tirzepatide-related acute liver injury. Eur J Case Rep Intern Med. 2024;11:004813.. [PMC free article: PMC11379107] [PubMed: 39247248](24 year old obese woman developed abdominal pain 4.5 months after starting tirzepatide for weight loss and, while liver tests were initially normal, within days they rose precipitously [ALT 6212 U/L, AST 6712 U/L, Alk P 132 U/L, bilirubin 7.3 mg/dL, INR 9] and rapidly resolved after tirzepatide was stopped).
- Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A, Sands SA, et al; SURMOUNT-OSA Investigators. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391:1193-1205.. [PMC free article: PMC11598664] [PubMed: 38912654](Among 467 obese adults with obstructive sleep apnea treated for 52 weeks in 2 controlled trials, there was greater weight loss and decrease in apneic events with tirzepatide than placebo, and there were no hepatic adverse events).
- Sohal A, Casanova L, Kowdley KV. A rare case of tirzepatide-induced hepatotoxicity. ACG Case Rep J. 2024;11:e01484.. [PMC free article: PMC11452087] [PubMed: 39372916](37 year old woman developed elevated serum aminotransferase levels 12 weeks after starting tirzepatide for weight loss [ALT 500 U/L, bilirubin and Alk P not provided] with improvement on stopping [ALT 110 U/L], worsening again on restarting [ALT 184 U/L], and ultimately resolving 2 months with stopping again [ALT 24 U/L).
- Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, Menon V, Ge J, et al; SUMMIT Trial Study Group. Tirzepatide for heart failure with preserved ejection fraction and obesity. N Engl J Med. 2025;392:427-437.. [PubMed: 39555826](Among 731 obese adults with heart failure with preserved ejection fraction who were treated for 52 weeks, death from cardiovascular disease or worsening heart failure was less with tirzepatide [10%] than placebo [15%] while adverse event rates were similar, serious adverse events occurring in 26.4% vs 25.6% of patients; no mention of ALT elevations or hepatotoxicity).
- Jastreboff AM, le Roux CW, Stefanski A, Aronne LJ, Halpern B, Wharton S, Wilding JPH, et al; SURMOUNT-1 Investigators. Tirzepatide for obesity treatment and diabetes prevention. N Engl J Med. 2025;392:958-971.. [PubMed: 39536238](Among 2539 obese adults treated with 5, 10, or 15 mg of tirzepatide or placebo subcutaneously once weekly for 3 years, tirzepatide treated resulted in greater weight loss [-12% to -20% vs -1.3%] and a lower rate of new onset of diabetes [1.3% vs 13.3%], while both overall [85% to 88% vs 83%] and serious adverse event rates [13% to 15% vs 12%] were similar, and serum ALT and AST levels decreased with tirzepatide but remained unchanged with placebo treatment).
- Phox M, Thesing J, Kilgore WR 3rd, Alderson J. Tirzepatide-induced liver injury: a rare medication side effect. ACG Case Rep J. 2025;12:e01661.. [PMC free article: PMC11984778] [PubMed: 40212859](76 year old obese woman developed fatigue and dark urine 7 weeks after starting tirzepatide for weight loss [bilirubin 3.0 mg/dL, ALT 486 U/L, Alk P 73 U/L], biopsy showing lobular inflammation and injury, and abnormalities resolving within 2 months of stopping tirzepatide).
- Look M, Dunn JP, Kushner RF, Cao D, Harris C, Gibble TH, Stefanski A, et al. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. Diabetes Obes Metab. 2025;27:2720-2729.. [PMC free article: PMC11965027] [PubMed: 39996356](Among 160 obese adults treated with tirzepatide or placebo who underwent DXA scans before and after 72 weeks of treatment, weight loss was greater with tirzepatide but the proportion of lean vs fat mass loss [approximately 25% vs 75%] was the same in the two groups).
- Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, Das S, et al; SURMOUNT-5 Trial Investigators. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025 May 11. Epub ahead of print.. [PubMed: 40353578](Among 781 obese adults without diabetes treated with tirzepatide vs semaglutide for 72 weeks, weight loss was greater with tirzepatide [-20% vs -14%] while both overall [77% vs 79%] and serious events [4.8% vs 3.5%] were similar; no mention of ALT elevations or hepatic adverse events).
- PMCPubMed Central citations
- PubChem SubstanceRelated PubChem Substances
- PubMedLinks to PubMed
- The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect.[Cardiovasc Diabetol. 2021]The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect.Fisman EZ, Tenenbaum A. Cardiovasc Diabetol. 2021 Nov 24; 20(1):225. Epub 2021 Nov 24.
- Review Beyond weight loss: tirzepatide as a dual GIP/GLP-1 receptor agonist for obstructive sleep apnea.[Curr Opin Endocrinol Diabetes ...]Review Beyond weight loss: tirzepatide as a dual GIP/GLP-1 receptor agonist for obstructive sleep apnea.Noreña JA, Akcan T, Desai D. Curr Opin Endocrinol Diabetes Obes. 2026 Jun 1; 33(3):108-114. Epub 2025 Dec 17.
- Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, exhibits favourable effects on pancreatic β-cells and hepatic steatosis in obese type 2 diabetic db/db mice.[Diabetes Obes Metab. 2024]Tirzepatide, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, exhibits favourable effects on pancreatic β-cells and hepatic steatosis in obese type 2 diabetic db/db mice.Iwamoto Y, Kimura T, Dan K, Iwamoto H, Sanada J, Fushimi Y, Katakura Y, Shimoda M, Yamasaki Y, Nogami Y, et al. Diabetes Obes Metab. 2024 Dec; 26(12):5982-5994. Epub 2024 Sep 30.
- [SURMOUNT-OSA study : tirzepatide improves obstructive sleep apnoea in patients with obesity].[Rev Med Liege. 2025][SURMOUNT-OSA study : tirzepatide improves obstructive sleep apnoea in patients with obesity].Scheen A. Rev Med Liege. 2025 Apr; 80(4):251-257.
- Review [Tirzepatide : overview of clinical studies SURPASS in type 2 diabetes and SURMOUNT in obesity].[Rev Med Liege. 2024]Review [Tirzepatide : overview of clinical studies SURPASS in type 2 diabetes and SURMOUNT in obesity].Scheen A. Rev Med Liege. 2024 Dec; 79(12):812-820.
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