Adverse Events Related to Tirzepatide
Open accessAbstract
Context: Tirzepatide is a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the US Food and Drug Administration in May 2022 for patients with type 2 diabetes mellitus (T2DM). Objective: We aimed to determine the rates of individual adverse events (AEs) related to 3 studied doses of tirzepatide. Methods: We performed a systematic review with meta-analysis including 5 databases (PubMed, Embase, CINAHL, Scopus, and Web of Science) for all clinical trials reporting AEs related to tirzepatide. The safety data from individual studies were extracted and analyzed through meta-regression to assess rates of individual AEs. Study quality assessment was performed using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Ten trials (6836 participants) were included. Gastrointestinal (GI) AEs were the most commonly reported AEs and were dose dependent 39% (95% CI, 35%-43%), 46% (95% CI, 42%-49%), and 49% (95% CI, 38%-60%) for the 5, 10, and 15 mg dose, respectively. Among all GI AEs, nausea and diarrhea were most frequent at any dose of tirzepatide. Drug discontinuation due to AEs was highest with the 15 mg dose of tirzepatide (10%). Incidence of mild hypoglycemia (blood glucose < 70 mg/dL) was highest with tirzepatide 10 mg dose 22.6% (9.2%-39.8%). Rates of fatal AEs, severe hypoglycemia, acute pancreatitis, cholelithiasis, and cholecystitis were extremely low (≤ 1%) across all doses of tirzepatide. Conclusion: Tirzepatide is associated with a dose-dependent increase in incidence of GI AEs and AEs leading to drug discontinuation. Severe hypoglycemia, fatal AEs, acute pancreatitis, cholelithiasis, and cholecystitis are rare with this medication.
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The use of semaglutide and tirzepatide may increase the risk of biliary disorders such as cholelithiasis, a risk similar to that of other GLP-1 receptor agonists.
“The use of semaglutide and tirzepatide may increase the risk of biliary disorders such as cholelithiasis, a risk similar to that of other GLP-1 receptor agonists, and therefore patients should be monitored during clinical use [89,90].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [90]
The Results section (Incidence of Gallbladder and Pancreatic Adverse Events; page unavailable) reports cholelithiasis and cholecystitis among tirzepatide users, but describes cholelithiasis as rare and its pooled proportion as nonsignificant. The Conclusion (page unavailable) says tirzepatide has a similar overall adverse-event profile to GLP-1 receptor agonists. The paper does not establish an increased biliary-disorder risk or make that comparison specifically for biliary disorders, and it does not report a semaglutide-specific risk. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn clinical trials, severe hypoglycemia, acute pancreatitis, gallstones, and cholecystitis occurred rarely and were observed only in a few cases during the use of high-dose semaglutide and tirzepatide.
“In clinical trials, severe hypoglycemia, acute pancreatitis, gallstones, and cholecystitis occurred rarely and were observed only in a few cases during the use of high-dose semaglutide and tirzepatide [89,90].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [90]
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Cites
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes
Frías, J. P., Davies, M. J., Rosenstock, J., Pérez Manghi, F. C., Fernández Landó, L., Bergman, B. K., Liu, B., Cui, X., & Brown, K. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2107519 · Cited by 2,096 · see citing works
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868 · see citing works
Coskun, T., Sloop, K. W., Loghin, C., Alsina-Fernandez, J., Urva, S., Bokvist, K. B., Cui, X., Briere, D. A., Cabrera, O., Roell, W. C., et al. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.09.009 · Cited by 882 · see citing works
Frias, J. P., Nauck, M. A., Van, J., Kutner, M. E., Cui, X., Benson, C., Urva, S., Gimeno, R. E., Milicevic, Z., Robins, D., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)32260-8 · Cited by 815 · cited 8× · see citing works
“Five studies [14, 16, 19, 21, 22] with a placebo arm had a similar pooled proportion for acute pancreatitis of 0.”
BackgroundInfluentialDahl, D., Onishi, Y., Norwood, P., Huh, R., Bray, R., Patel, H., & Rodríguez, Á. (2022) · JAMA · doi:10.1001/jama.2022.0078 · Cited by 597 · cited 8× · see citing works
“The SURPASS-5 trials showed that diarrhea, nausea, and vomiting were the most common treatment-emergent adverse events (AEs) in the groups receiving tirzepatide; however, the incidence of new AEs decreased over time in the groups and there were no deaths were recorded during the study [16].”
BackgroundInfluentialBlonde, L., Umpierrez, G. E., Reddy, S. S., McGill, J. B., Berga, S. L., Bush, M., Chandrasekaran, S., DeFronzo, R. A., Einhorn, D., Galindo, R. J., et al. (2022) · Endocrine Practice · doi:10.1016/j.eprac.2022.08.002 · Cited by 507 · cited 1× · see citing works
“GLP-1 receptor agonists (GLP-1 RAs) have been approved for the treatment of T2DM since 2005 and are recommended, as per the latest guidelines, early in the treatment algorithm given the associated weight reduction, glycemic efficacy, and favorable cardio-nephrovascular outcomes [7, 8].”
BackgroundGlucose-Dependent Insulinotropic Polypeptide
Christensen, M., Vedtofte, L., Holst, J. J., Vilsbøll, T., & Knop, F. K. (2011) · Diabetes · doi:10.2337/db11-0979 · Cited by 353 · see citing works
Gasbjerg, L. S., Helsted, M. M., Hartmann, B., Jensen, M. H., Gabe, M. B. N., Sparre-Ulrich, A. H., Veedfald, S., Stensen, S., Lanng, A. R., Bergmann, N. C., et al. (2019) · Diabetes · doi:10.2337/db18-1123 · Cited by 193 · see citing works
Permana, H., Yanto, T. A., & Hariyanto, T. I. (2022) · Diabetes & Metabolic Syndrome: Clinical Research & Reviews · doi:10.1016/j.dsx.2022.102640 · Cited by 38 · see citing works
Flagged first, then by citations
Research works printed but not linked: 22
- [1]Kim W, Egan JM. The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev. 2008; 60(4): 470– 512. 19074620 PMC2696340
- [2]Elrick H, Stimmler L, Hlad CJ Jr, Arai Y. Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab. 1964; 24(10): 1076– 1082. 14228531
- [3]Creutzfeldt W. The incretin concept today. Diabetologia. 1979; 16(2): 75– 85. 32119
- [4]DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005; 28(5): 1092– 1100. 15855572
- [5]Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368(9548): 1696– 1705. 17098089
- [7]American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes–2022. Diabetes Care. 2022; 45(Suppl 1): S125– S143. 34964831
- [10]Nauck MA, Bartels E, Orskov C, Ebert R, Creutzfeldt W. Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. J Clin Endocrinol Metab. 1993; 76(4): 912– 917. 8473405
- [12]Yip RGC, Boylan MO, Kieffer TJ, Wolfe MM. Functional GIP receptors are present on adipocytes. Endocrinology. 1998; 139(9): 4004– 4007. 9724057
- [13]Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020; 31(6): 410– 421. 32396843
- [15]Min T, Bain SC. The role of tirzepatide, dual GIP and GLP-1 receptor agonist, in the management of type 2 diabetes: the SURPASS clinical trials. Diabetes Ther. 2021; 12(1): 143– 157. 33325008 PMC7843845
- [17]Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-analyses: the PRISMA statement. Ann Intern Med. 2009; 151(4): 264– 269, W64. 19622511
- [18]Urva S, Quinlan T, Landry J, Martin J, Loghin C. Effects of renal impairment on the pharmacokinetics of the dual GIP and GLP-1 receptor agonist tirzepatide. Clin Pharmacokinet. 2021; 60(8): 1049– 1059. 33778934 PMC8332596
- [19]Frías JP, Nauck MA, Van J, et al Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens. Diabetes Obes Metab. 2020; 22(6): 938– 946. 31984598 PMC7318331
- [20]Raj R. Study Quality Assessment—Adverse Events Related to Tirzepatide. V1 ed. Harvard Dataverse; 2023. PMC9915969 36789109
- [21]Rosenstock J, Wysham C, Frías JP, 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. 34186022
- [24]Del Prato S, Kahn SE, Pavo I, 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. 34672967
- [25]Ludvik B, Giorgino F, Jódar E, 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. 34370970
- [26]Furihata K, Mimura H, Urva S, Oura T, Ohwaki K, Imaoka T. A phase 1 multiple-ascending dose study of tirzepatide in Japanese participants with type 2 diabetes. Diabetes Obes Metab. 2022; 24(2): 239– 246. 34647404 PMC9299227
- [27]Yu Y, Hu G, Yin S, Yang X, Zhou M, Jian W. Optimal dose of tirzepatide for type 2 diabetes mellitus: a meta-analysis and trial sequential analysis. Front Cardiovasc Med. 2022; 9: 990182. PMC9472131 36119737
- [28]Karagiannis T, Avgerinos I, Liakos A, et al Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis. Diabetologia. 2022; 65(8): 1251– 1261. 35579691 PMC9112245
- [29]Dutta D, Surana V, Singla R, Aggarwal S, Sharma M. Efficacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: a Cochrane meta-analysis. Indian J Endocrinol Metab. 2021; 25(6): 475– 489. 35355921 PMC8959203
- [30]Bhagavathula AS, Vidyasagar K, Tesfaye W. Efficacy and safety of tirzepatide in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized phase II/III trials. Pharmaceuticals (Basel). 2021; 14(10): 991. 34681215 PMC8537322
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RETRACTED: Tirzepatide and exercise training in obesity
Bagherzadeh-Rahmani, B., Marzetti, E., Karami, E., Campbell, B. I., Fakourian, A., Haghighi, A. H., Mousavi, S. H., Heinrich, K. M., Brazzi, L., Jung, F., et al. (2024) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-242134 · Cited by 21 · see citing works
RetractedWen, J., Syed, B., Nadora, D., How‐Volkman, C., Bernstein, E., Truong, A., Akhtar, M., Razick, A., Puglisi, J., & Frezza, E. (2025) · Endocrinology, Diabetes & Metabolism · doi:10.1002/edm2.70045 · Cited by 17 · see citing works
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Dissanayake, H. A., & Somasundaram, N. P. (2024) · Current Diabetes Reports · doi:10.1007/s11892-023-01530-2 · Cited by 8 · see citing works
- Authors
- Mishra, R., Raj, R., Elshimy, G., Zapata, I., Kannan, L., Majety, P., Edem, D., & Correa, R.
- Affiliations
- Cleveland Clinic (US)
- Pikeville Medical Center (US)
- Augusta University (US)
- Rocky Vista University (US)
- Virginia Commonwealth University (US)
- University of Arkansas for Medical Sciences (US)
- Corresponding author
- Raj, Rishi
- ORCID
- Venue
- Journal of the Endocrine Society
- Publisher
- The Endocrine Society
- Published
- 2023-01-26
- Volume
- 7
- Issue
- 4
- Pages
- bvad016-bvad016
- ISSN
- 2472-1972 (ISSN-L)
- PMC
- PMC9915969
- OpenAlex
- W4318184530
- Cited by
- 110
- References
- 9
- Citations by year
- 2026: 37 · 2025: 36 · 2024: 28 · 2023: 9
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the Endocrine Society (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- tirzepatide, adverse events, drug safety, type 2 diabetes, GIP/GLP-1 receptor agonist, gastrointestinal adverse effects, nausea, diarrhea, hypoglycemia, drug discontinuation, acute pancreatitis, gallstones, cholecystitis
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