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Trulicity ® (dulaglutide) injection
0.75 mg/0.5 mL, 1.5 mg/0.5 mL, 3mg/0.5mL, 4.5mg/0.5mL
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 Trulicity® (dulaglutide) be used in patients with gastroparesis?
Dulaglutide has not been studied in patients with severe or preexisting gastroparesis, and is therefore not recommended in these patients.
See important safety information, including boxed warning, in the attached prescribing information.
Dulaglutide and Delayed Gastric Emptying
Dulaglutide causes a delay of gastric emptying. The delay in gastric emptying is dose dependent but is attenuated with adequate dose escalation to higher doses of dulaglutide. The delay is largest after the first dose and diminishes with subsequent doses.1
This delay in gastric emptying is associated with reductions in postprandial glucose concentrations in patients with type 2 diabetes. Therefore, the pharmacodynamic effect of delayed gastric emptying is an important factor that contributes to the efficacy of dulaglutide.2
Dulaglutide Use in Patients With Gastroparesis
The use of dulaglutide may be associated with gastrointestinal adverse reactions, which may be sometimes severe.1
Patients with significant gastric emptying abnormality, such as severe gastroparesis, were excluded from the AWARD studies, REWIND study, and AWARD-PEDS clinical trials.2-8
Gastroparesis is a motility disorder characterized by symptoms and objective documentation of delayed gastric emptying of solid food without mechanical obstruction, which should be excluded by imaging studies such as upper gastrointestinal endoscopy or radiology.9
Symptoms include early satiety, nausea, vomiting, bloating, upper abdominal discomfort, postprandial fullness, and weight loss.2,10
The gold standard for diagnosing gastroparesis is gastric emptying scintigraphy. Alternative diagnostic tests for gastroparesis include nonradioactive 13C-labeled gastric emptying breath test and wireless motility capsule.2,12,13
Dulaglutide has not been studied in patients with severe gastrointestinal disease, including severe or preexisting gastroparesis, and is therefore not recommended in these patients.1
Gastroparesis as an Adverse Event in Patients Taking Dulaglutide
Clinical Trial Data
Throughout this document, "potential gastroparesis events" has been used to refer to any of the events that met the search criteria for gastroparesis events as defined by the following Medical Dictionary for Regulatory Activities (MedDRA) preferred terms of
- bezoar
- diabetic gastroparesis
- diabetic gastropathy
- endoscopy upper gastrointestinal tract
- endoscopy upper gastrointestinal tract abnormal
- gastric atony
- gastric emptying study
- gastric hypomotility
- gastric residual increased
- gastrointestinal hypomotility
- gastrointestinal motility disorder
- gastroparesis postoperative
- impaired gastric emptying, and
- regurgitation.2
In order to identify potential events of gastroparesis, an intentionally broad search strategy was utilized that included diagnostic tests, symptoms, and sequelae that may be associated with gastroparesis. As a result, some adverse events may be included that are not gastroparesis. There were no events of bezoar, endoscopy upper gastrointestinal tract abnormal, gastric atony, gastric emptying study, gastric residual increased, or gastroparesis postoperative identified in the search of the clinical trial database.2
The clinical trial database was searched for potential gastroparesis events across all 27 completed controlled phase 2, 3, and 4 studies of dulaglutide as of October 31, 2023.2
In 24 Completed Phase 2, 3, and 4 Glycemic Control Studies
In 24 completed phase 2, 3, and 4 glycemic control studies of dulaglutide in adults (except AWARD-7), at least 1 potential gastroparesis treatment-emergent adverse event (TEAE) was reported in
- 21 of 9882 (0.21%) patients while receiving dulaglutide
- 1 of 1152 (0.09%) patients while receiving another incretin, and
- 1 of 1502 (0.07%) patients while receiving a nonincretin.2
No patients experienced these potential gastroparesis events while on placebo.2
One of the above-mentioned events was a serious adverse event (SAE), which occurred in a patient receiving dulaglutide, but was not fatal.2
In AWARD-7
AWARD-7 was a randomized, multicenter, open-label (blinded for the dose of dulaglutide), 52-week study that compared the efficacy and safety of once-weekly dulaglutide 1.5 mg or once-weekly dulaglutide 0.75 mg versus daily insulin glargine, all in combination with insulin lispro, for the treatment of patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD).5
The search identified a total of 2 of 382 (0.52%) patients who experienced at least 1 potential gastroparesis TEAE while on dulaglutide.2
None of the patients experienced a potential gastroparesis TEAE while receiving insulin glargine.2
There was no SAE reported related to potential gastroparesis event.2
In REWIND
REWIND was a long-term cardiovascular outcome trial conducted in older patients with type 2 diabetes at increased cardiovascular risk with a median follow-up time of 5.4 years.7,14
Adverse event, n (%) |
Dulaglutide 1.5 mg (N=4943) |
Placebo (N=4949) |
Total (N=9892) |
TEAE |
28 (0.57) |
18 (0.36) |
46 (0.47) |
SAE |
2 (0.04) |
1 (0.02) |
3 (0.03) |
Abbreviations: SAE = serious adverse event; TEAE = treatment-emergent adverse event.
There were no fatalities associated with these events.2
The search identified that events of prolonged potential gastroparesis (ie, the patient had not recovered at the final study disposition) occurred in
- 18 of 4943 (0.36%) patients who received dulaglutide 1.5 mg, and
- 10 of 4949 (0.20%) patients who received placebo.2
In AWARD-PEDS
AWARD-PEDS was a phase 3, randomized, placebo-controlled study that assessed the efficacy and safety of dulaglutide 0.75 mg and 1.5 mg in pediatric patients, ages 10 to less than 18 years old, with inadequately controlled type 2 diabetes despite diet and exercise, with or without metformin and/or basal insulin.8
In AWARD-PEDS, no events of potential gastroparesis were reported in the dulaglutide or placebo arms.2
Postmarketing (Spontaneous) Adverse Event Reports
Postmarketing data do not necessarily represent the rate of occurrence of an adverse event in a treated population, but they represent a reporting rate of a particular adverse event to the company. Spontaneous reporting of adverse events can be highly variable and is not appropriately controlled clinical information on which to base an assessment of whether a particular drug product is the causal agent of an adverse event.2
Spontaneous reporting has limited use due to
- lack of control population
- under-reporting or reporting bias, and
- missing or incomplete information regarding patient's medical history or concomitant medications.2
The Eli Lilly and Company (Lilly) spontaneous adverse event database may also include reports of adverse events for products that may be available from Lilly and from other manufacturers. Although verification of product manufacturer is sought, this verification is not always obtainable. The default for these cases is to include them in the database.2
Through September 18, 2023, adverse events with the MedDRA preferred terms of bezoar, diabetic gastroparesis, diabetic gastropathy, gastric atony, gastric hypomotility, gastric residual increased, gastrointestinal hypomotility, gastrointestinal motility disorder, impaired gastric emptying, and regurgitation have been Very Rarely Reported in the Lilly spontaneous adverse event database, based on the estimated exposure of 18,398,000 patients. Very Rarely Reported is defined as an adverse event that has been reported at an estimated rate of <0.01% according to the reporting system information.2
Adverse events with the preferred terms of endoscopy upper gastrointestinal tract, endoscopy upper gastrointestinal tract abnormal, gastric emptying study, and gastroparesis postoperative were not present in the Lilly spontaneous adverse event database through September 18, 2023.2
Patient safety is Eli Lilly and Company’s top priority, and we actively engage in monitoring, evaluating, and reporting safety information for all our medicines.
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Trulicity [package insert]. Indianapolis, IN: Eli Lilly and Company; 2022.
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3A study in participants with type 2 diabetes mellitus (AWARD-1). ClinicalTrials.gov identifier: NCT01064687. Updated January 26, 2015. Accessed January 29, 2024. https://clinicaltrials.gov/show/NCT01064687
4Blonde L, Jendle J, Gross J, et al. Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study. Lancet. 2015;385(9982):2057-2066. https://doi.org/10.1016/S0140-6736(15)60936-9
5Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018;6(8):605-617. https://doi.org/10.1016/S2213-8587(18)30104-9
6Frias JP, Bonora E, Nevarez Ruiz L, et al. Efficacy and safety of dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5 mg in metformin-treated patients with type 2 diabetes in a randomized controlled trial (AWARD-11). Diabetes Care. 2021;44(3):765-773. https://doi.org/10.2337/dc20-1473
7Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130. https://doi.org/10.1016/S0140-6736(19)31149-3
8Arslanian SA, Hannon T, Zeitler P, et al; AWARD-PEDS Investigators. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022;387(5):433-443. https://doi.org/10.1056/NEJMoa2204601
9Camilleri M, Kuo B, Nguyen L, et al. ACG clinical guideline: gastroparesis. Am J Gastroenterol. 2022;117(8):1197-1220. https://doi.org/10.14309/ajg.0000000000001874
10Camilleri M, Parkman HP, Shafi MA, et al. American College of Gastroenterology. Clinical guideline: management of gastroparesis. Am J Gastroenterol. 2013;108(1):18-38. https://doi.org/10.1038%2Fajg.2012.373
11Cai JX, Chan WW. Disorders of gastric & small bowel motility. In: Friedman S, Blumberg RS, Saltzman J, editors. Greenberger’s CURRENT Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy. 4th ed. McGraw Hill; 2022.
12Kalas MA, Dang TQ, Galura G, et al. Frequency of GLP-1 receptor agonists use in diabetic patients diagnosed with delayed gastric emptying and their demographic profile. J Investig Med. 2023;71(1):11-16. https://doi.org/10.1136/jim-2022-002480
13Lacy BE, Tack J, Gyawali CP. AGA clinical practice update on management of medically refractory gastroparesis: expert review. Clin Gastroenterol Hepatol. 2022;20(3):491-500. https://doi.org/10.1016/j.cgh.2021.10.038
14Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Trial Investigators. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018;20(1):42-49. https://doi.org/10.1111/dom.13028
Date of Last Review: January 25, 2024