Adverse Events Related to Tirzepatide

Abstract

Objective Tirzepatide is a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the Food and Drug Administration (FDA) in May 2022 for patients with type 2 diabetes mellitus (T2DM). We aimed to determine the rates of individual adverse events (AEs) related to 3 studied doses of tirzepatide. Methods We performed a Systematic Review with Meta-analysis including five databases (PubMed, Embase, CINAHL, Scopus and Web of Science), for all clinical trials reporting AEs related to tirzepatide. The safety data from individual studies were extracted and analyzed through meta-regression to assess rates of individual adverse events. Study quality assessment was done using National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results Ten trials (6836 participants) were included. Gastrointestinal AEs were the most commonly reported AEs and were dose-dependent 39% (95% CI: 35-43), 46% (95% CI: 42-49), and 49% (95% CI: 38-60) for 5 mg, 10 mg, and 15 mg dose, respectively. Among all gastrointestinal AEs, nausea and diarrhea were most frequent at any dose of tirzepatide. Drug discontinuation due AEs was highest with 15 mg dose of tirzepatide (10%). Incidence of mild hypoglycemia (blood glucose <70 mg/dL) was highest with tirzepatide 10 mg dose 22.6% (9.2- 39.8%). Rates of fatal AEs, severe hypoglycemia, acute pancreatitis, cholelithiasis, and cholecystitis were extremely low (≤1%) across all doses of tirzepatide. Conclusion Tirzepatide is associated with dose-dependent increase in incidence of gastrointestinal AEs and AEs leading to drug discontinuation. Severe hypoglycemia, fatal AEs, acute pancreatitis, cholelithiasis, and cholecystitis are rare with this medication.