See important safety information, including boxed warning, in the attached prescribing information.

Tirzepatide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.1

The use of tirzepatide has been associated with gastrointestinal adverse reactions, sometimes severe. In a pool of 2 tirzepatide clinical studies for weight reduction (SURMOUNT-1 and SURMOUNT-2), severe gastrointestinal adverse reactions were reported more frequently among patients receiving tirzepatide (5 mg 1.7%, 10 mg 2.5%, 15 mg 3.1%) than placebo (1%).1 

Similar rates of severe gastrointestinal adverse reactions were observed in tirzepatide clinical studies for weight reduction and obstructive sleep apnea.1

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.2

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 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

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

ZEPBOUND® (tirzepatide) injection, for subcutaneous use, Lilly

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).