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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.
What is the effect of Trulicity® (dulaglutide) on gastric emptying?
Dulaglutide delays gastric emptying and caution should be taken when dulaglutide is concomitantly administered with oral medications.
See important safety information, including boxed warning, in the attached prescribing information.
Introduction
Dulaglutide delays gastric emptying and has the potential to reduce the extent and rate of absorption of concomitantly administered oral medications. The delay in gastric emptying is dose-dependent but is attenuated with the recommended dose escalation to higher doses of dulaglutide. The delay is largest after the first dose and diminishes with subsequent doses.1
In clinical pharmacology studies, dulaglutide 1.5 mg did not affect the absorption, to any clinically relevant degree, of the tested orally administered medications that included
- lisinopril
- metoprolol
- digoxin
- norelgestromin
- ethinylestradiol
- atorvastatin
- metformin
- acetaminophen
- S-warfarin
- R-warfarin, and
- sitagliptin.1
Precautions
Caution should be exercised when oral medications are concomitantly administered with dulaglutide. Drug levels of oral medications with a narrow therapeutic index such as warfarin should be adequately monitored when concomitantly administered with dulaglutide.1
Dulaglutide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is, therefore, not recommended in these patients.1
Clinical Pharmacology Studies
In clinical pharmacology studies, dulaglutide 1.5 mg did not affect the absorption of the tested orally administered medications to a clinically relevant degree. There is limited experience with the use of concomitant medications in clinical trials with dulaglutide doses of 3 mg and 4.5 mg.1
The gastric emptying delay with dulaglutide administration has been demonstrated in 3 clinical pharmacology studies.2,3
In the first study, patients with type 2 diabetes were assigned to 1 of 6 dulaglutide doses that included
- 0.05 mg
- 0.3 mg
- 1 mg
- 3 mg
- 5 mg, and
- 8 mg.2
On 2 occasions, oral acetaminophen was administered and gastric emptying was assessed by following the absorption of acetaminophen.2
The maximum average delay in time to maximum plasma concentration (tmax) of acetaminophen was approximately 1.5 hours, and there was a significant difference in the least squares mean (LSM) ratio of predose to postdose tmax observed between dulaglutide 8 mg and placebo (tmax, 2.31; 90% CI: 1.28, 4.18). The results of the study suggested that gastric emptying was delayed by treatment with dulaglutide.2
In the second study, healthy subjects were assigned to dulaglutide 1 mg or dulaglutide 3 mg and received acetaminophen on 2 occasions to assess acetaminophen pharmacokinetics. Steady-state levels of dulaglutide had no clinically significant effect on the rate or extent of gastric emptying according to the pharmacokinetics of acetaminophen. However, the rate of gastric emptying was decreased after the first dose of dulaglutide 1mg or 3 mg, which
- reduced maximum plasma concentration (Cmax) of acetaminophen by 36% and 50%, respectively, and
- significantly delayed the tmax of acetaminophen by 3 and 4 hours, respectively.3
In the third study, scintigraphy was used in patients with type 2 diabetes to assess t50, defined as the time required for 50% of activity from a radiolabeled meal to empty from the stomach. Compared with baseline, statistically significant delays in gastric emptying rate were observed following each of 4 dulaglutide 1.5 mg doses. The effect was most pronounced after the first dose of dulaglutide, with
- a mean increase in t50 from 1.72 hours (on day 3, after placebo) to 3.77 hours (on day 10, after the first dose of dulaglutide), and
- a corresponding 2.4-fold increase in area under the curve (AUC, residual activity).3
The results demonstrated that dulaglutide treatment delays gastric emptying by approximately 2 hours where the effect is largest after the first dose and diminishes with subsequent doses.3
Enclosed Prescribing Information
References
The published reference below is available by contacting 1-800-LillyRx (1-800-545-5979).
1Trulicity [package insert]. Indianapolis, IN: Eli Lilly and Company; 2022.
2Barrington P, Chien JY, Showalter HDH, et al. A 5-week study of the pharmacokinetics and pharmacodynamics of LY2189265, a novel, long-acting glucagon-like peptide-1 analogue, in patients with type 2 diabetes. Diabetes Obes Metab. 2011;13(5):426-433. https://doi.org/10.1111/j.1463-1326.2011.01364.x
3Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: May 22, 2023