Adverse Events Related to Tirzepatide.

Area of Science:

• Endocrinology
• Pharmacology
• Clinical Trials

Background:

• Tirzepatide is an FDA-approved dual GIP and GLP-1 receptor agonist for type 2 diabetes mellitus (T2DM).
• Understanding the adverse event (AE) profile across different tirzepatide doses is crucial for clinical practice.

Purpose of the Study:

• To systematically review and meta-analyze the rates of individual adverse events associated with 5, 10, and 15 mg doses of tirzepatide.
• To assess the dose-dependency of adverse events and drug discontinuations.

Main Methods:

• A systematic review and meta-analysis of 5 major databases (PubMed, Embase, CINAHL, Scopus, Web of Science) were conducted.
• Safety data from 10 clinical trials involving 6836 participants were extracted and analyzed using meta-regression.
• Study quality was assessed using the NHLBI Quality Assessment Tool.

Main Results:

• Gastrointestinal (GI) adverse events, including nausea and diarrhea, were the most frequent and dose-dependent, increasing with higher tirzepatide doses.
• Drug discontinuation due to AEs was highest at the 15 mg dose (10%).
• Mild hypoglycemia occurred most frequently with the 10 mg dose (22.6%). Rates of severe hypoglycemia, fatal AEs, pancreatitis, and gallstones were very low (≤1%).

Conclusions:

• Tirzepatide use is associated with a dose-dependent increase in GI adverse events and discontinuations.
• Serious adverse events such as severe hypoglycemia, acute pancreatitis, and cholelithiasis are rare across all studied doses of tirzepatide.