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Review
. 2023 Jan 26;7(4):bvad016.
doi: 10.1210/jendso/bvad016. eCollection 2023 Feb 9.

Adverse Events Related to Tirzepatide

Rahul Mishra  1 , Rishi Raj  2 , Ghada Elshimy  3 , Isain Zapata  4 , Lakshmi Kannan  5 , Priyanka Majety  6 , Dinesh Edem  7 , Ricardo Correa  8
Affiliations
Review

Adverse Events Related to Tirzepatide

Rahul Mishra et al. J Endocr Soc. .

Abstract

Context: Tirzepatide is a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the US Food and Drug Administration in May 2022 for patients with type 2 diabetes mellitus (T2DM).

Objective: 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 5 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 AEs. Study quality assessment was performed using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.

Results: Ten trials (6836 participants) were included. Gastrointestinal (GI) 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 the 5, 10, and 15 mg dose, respectively. Among all GI AEs, nausea and diarrhea were most frequent at any dose of tirzepatide. Drug discontinuation due to AEs was highest with the 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 a dose-dependent increase in incidence of GI AEs and AEs leading to drug discontinuation. Severe hypoglycemia, fatal AEs, acute pancreatitis, cholelithiasis, and cholecystitis are rare with this medication.

Keywords: LY3298176; adverse events; diabetes; dual GIP/GLP-1 receptor agonist; glucose; meta-analysis; safety; systematic review; tirzepatide.

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Figures

Figure 1.
Figure 1.
PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram of the study selection process.
Figure 2.
Figure 2.
Incidence (%) of serious adverse events, fatal adverse events, and adverse events leading to treatment discontinuation with tirzepatide 5, 10, and 15 mg, respectively.
See this image and copyright information in PMC

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