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Zepbound ® (tirzepatide) injection
2.5 mg/ 5 mg/ 7.5 mg/ 10 mg/ 12.5 mg/ 15 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
Can Zepbound® (tirzepatide) be used in patients with gastroparesis?
Tirzepatide has not been studied in people with severe gastroparesis and is therefore not recommended in these patients.
See important safety information, including boxed warning, in the attached prescribing information.
Prescribing Information Related to Tirzepatide and Gastroparesis
The use of tirzepatide has been associated with gastrointestinal adverse reactions, sometimes severe.1
Tirzepatide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.1
Clinical Trial Data
In the completed phase 2 and phase 3 studies from the type 2 diabetes and chronic weight management clinical trial programs, at least 1 treatment-emergent adverse event (TEAE) of gastroparesis and related events were reported by
- 38 (0.43%) of the 8830 participants receiving tirzepatide
- 2 (0.19%) of the 1077 participants receiving placebo
- 1 (0.15%) of the 682 participants receiving GLP-1 receptor agonist comparator, and
- 0 of the 2288 participants receiving a non-glucagon-like peptide-1 (GLP-1) receptor agonist comparator.2
In this analysis, gastroparesis and related events included the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms of regurgitation, impaired gastric emptying, gastrointestinal motility disorder, diabetic gastroparesis, diabetic gastropathy, endoscopy upper gastrointestinal tract, and gastrointestinal hypomotility.2
Of these TEAEs, 1 case was considered serious in the tirzepatide arm and 1 in the placebo arm.2
Eli Lilly and Company has reviewed clinical data of patients reporting at least 1 TEAE of gastroparesis-related events in completed studies. This review did not provide evidence of a causal association between tirzepatide and gastroparesis. However, considering patients with known clinically significant gastric emptying abnormality including severe gastroparesis were excluded from clinical trials, the mechanistic plausibility with the known effect of delaying gastric emptying, and the fact the cases have been observed with tirzepatide, Lilly considers it as a potential risk.2
Postmarketing Data for Tirzepatide
Spontaneous reporting of adverse events can be highly variable and is not controlled clinical information on which to assess causality of a drug to an adverse event. Spontaneous reporting rates do not represent the rate of occurrence of an adverse event; they merely represent the rate of reporting of a particular adverse event to Lilly.2
As of May 13, 2024, spontaneous adverse events potentially related to tirzepatide were very rarely reported (<0.01%) including the MedDRA preferred terms of
- diabetic gastroparesis
- regurgitation
- impaired gastric emptying
- gastrointestinal motility disorder, and
- gastrointestinal hypomotility.2
Tirzepatide and Gastric Emptying Delay
Tirzepatide is a long-acting glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist.2
Tirzepatide delays gastric emptying. The delay is largest after the first dose and this effect diminishes over time.2
Clinical Trial Exclusion Criteria Related to Gastric Emptying
In the tirzepatide type 2 diabetes and chronic weight management clinical trial programs, participants were excluded if they
- had a known clinically significant gastric emptying abnormality such as severe diabetic gastroparesis or gastric outlet obstruction, or
- were chronically taking drugs that directly affect gastrointestinal motility.2-15
Enclosed Prescribing Information
References
1Zepbound [package insert]. Indianapolis, IN: Eli Lilly and Company; 2024.
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3Rosenstock 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. https://doi.org/10.1016/S0140-6736%2821%2901324-6
4Frías JP, Davies MJ, Rosenstock J, et al; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515. https://doi.org/10.1056/NEJMoa2107519
5Ludvik 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. https://doi.org/10.1016/S0140-6736(21)01443-4
6Del 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. https://doi.org/10.1016/S0140-6736(21)02188-7
7Dahl D, Onishi Y, Norwood P, et al. 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. https://doi.org/10.1001/jama.2022.0078
8Rosenstock J, Frías JP, Rodbard HW, et al. Tirzepatide vs insulin lispro added to basal insulin in type 2 diabetes: the SURPASS-6 randomized clinical trial. JAMA. 2023;330(17):1631-1640. https://doi.org/10.1001/jama.2023.20294
9Kadowaki T, Chin R, Ozeki A, et al. Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial. Lancet. 2022;10(9):634-644. https://doi.org/10.1016/S2213-8587(22)00187-5
10Inagaki N, Takeuchi M, Oura T, et al. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet. 2022;10(9):623-633. https://doi.org/10.1016/S2213-8587(22)00188-7
11Gao L, Lee BW, Chawla M, et al. Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial. Nat Med. 2023;29(6):1500-1510. https://doi.org/10.1038/s41591-023-02344-1
12Jastreboff AM, Aronne LJ, Ahmad NN, et al; SURMOUNT-1 Investigators. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. https://doi.org/10.1056/NEJMoa2206038
13Garvey WT, Frias JP, Jastreboff AM, et al; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402(10402):613-626. https://doi.org/10.1016/S0140-6736(23)01200-X
14Wadden TA, Chao AM, Machineni S, et al. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023;29(11):2909-2918. https://doi.org/10.1038/s41591-023-02597-w
15Aronne LJ, Sattar N, Horn DB, et al; SURMOUNT-4 Investigators. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024;331(1):38-48. https://doi.org/10.1001/jama.2023.24945
Date of Last Review: September 13, 2024