What are the common side effects of tirzepatide (Glucagon-like peptide-1 (GLP-1) receptor agonist)?

From the Guidelines

Tirzepatide commonly causes gastrointestinal side effects, including nausea, vomiting, diarrhea, and esophageal reflux, as well as injection site reactions and elevated heart rate, as reported in the most recent study 1.

Common Side Effects of Tirzepatide

The most frequent side effects of tirzepatide include:

• Gastrointestinal side effects such as nausea, vomiting, diarrhea, and esophageal reflux
• Injection site reactions
• Elevated heart rate
• Hypoglycemia These side effects are likely due to tirzepatide's mechanism of action as a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, which slows gastric emptying and affects gut hormone signaling 1.

Management of Side Effects

To minimize these side effects, patients can start with a low dose and gradually increase it (dose titration) 1. Additionally, patients should stay well-hydrated and consider smaller, more frequent meals to help manage gastrointestinal symptoms while their body adapts to the medication.

Important Safety Considerations

It is essential to monitor patients for potential consequences of delayed absorption of oral medications with narrow therapeutic indices, and to advise females using oral contraceptives to switch to a non-oral contraceptive method or add a barrier method of contraception for 4 weeks after initiation and dose escalations 1.

From the FDA Drug Label

5.5 Acute Kidney Injury MOUNJARO has been associated with gastrointestinal adverse reactions, which include nausea, vomiting, and diarrhea [see Adverse Reactions (6. 1)]. 5.6 Severe Gastrointestinal Adverse Reactions Use of MOUNJARO has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions 6.1]. 6.1 Adverse Reactions

The common side effects of trizepitide include:

• Gastrointestinal adverse reactions: nausea, vomiting, and diarrhea
• Severe gastrointestinal adverse reactions
• Hypoglycemia with concomitant use of insulin secretagogues or insulin
• Hypersensitivity reactions: anaphylaxis, angioedema
• Pancreatitis: acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis
• Acute kidney injury
• Acute gallbladder disease: cholelithiasis or cholecystitis 2

From the Research

Common Side Effects of Trizepitide

• Gastrointestinal side effects are common with trizepitide, including:
  • Nausea: incidence rate of 20.43% 3
  • Vomiting: incidence rate of 9.05% 3
  • Constipation: incidence rate of 2.54% 3
  • Decreased appetite: incidence rate of 9.64% 3
  • Diarrhea: incidence rate of 16.24% 3
  • Dyspepsia: incidence rate of 7.13% 3
• These side effects may negatively affect the drug's efficacy and patient tolerance 3
• The incidence of gastrointestinal side effects is positively correlated with the dose of trizepitide 4
• Gastrointestinal side effects of trizepitide decrease gradually over time, and long-term steady medication may be expected to reduce these side effects 4

Comparison with Other Treatments

• Trizepitide has a higher incidence of gastrointestinal side effects compared to placebo and insulin 4
• The incidence of gastrointestinal side effects with trizepitide is comparable to GLP-1 receptor agonists 4
• Trizepitide may have a lower risk of hypoglycemia compared to other antidiabetic drugs, but the risk is dependent on individual factors 5