Tirzepatide use linked to GI adverse events in dose dependant manner

The researchers revealed gastrointestinal adverse events to be the most commonly encountered AEs with incidence rates of up to 50% with the 15-mg dose of tirzepatide. For the majority of GI AEs, they found a dose-dependent relationship, with higher doses being associated with higher incidence rates of adverse events. The researchers note severe hypoglycemia, acute pancreatitis, fatal AEs, cholecystitis, and cholelithiasis to be rare with this medication.

Tirzepatide is a dual glucagon-like peptide-1 receptor agonist (GLP-1 RA) and glucose-dependent insulinotropic peptide (GIP) that got approval from the US Food and Drug Administration (FDA) in May 2022 for type 2 diabetes (T2D) patients.

Rahul Mishra, Cleveland Clinic Foundation, Cleveland, Ohio, USA, and colleagues aimed to determine the rates of individual adverse events related to 3 studied doses of tirzepatide. The study also evaluated rare adverse events linked with tirzepatide, including gall bladder and pancreatic adverse events besides common AEs associated with tirzepatide.

For this purpose, the researchers performed a systematic review with meta-analysis comprising five databases for all clinical trials reporting adverse events related to tirzepatide. From each study, they extracted safety data and analyzed it through meta-regression to assess rates of individual adverse events.

National Heart, Lung, and Blood Institute Quality Assessment Tool was used to perform study quality assessment. Ten trials consisting of 6836 participants were included.

The authors reported the following findings:

• Gastrointestinal AEs were the most commonly reported AEs and were dose-dependent at 39%, 46%, and 49% for the 5, 10, and 15 mg doses, respectively.
• Among all GI AEs, nausea and diarrhoea 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%.
• Rates of fatal AEs, severe hypoglycemia, acute pancreatitis, cholelithiasis, and cholecystitis were meagre (≤ 1%) across all doses of tirzepatide.

"We found gastrointestinal AEs to be the most common adverse events tied to tirzepatide use, including constipation, diarrhoea, decreased appetite, dyspepsia, vomiting, and nausea," the researchers wrote. "Tirzepatide was found to have a similar adverse events profile as GLP-1 RA."

They noted that, as evidenced by a dose-dependent HbA1c in prior studies, tirzepatide has been considered a great addition to next-generation medications for type 2 diabetes.

"Our study showed that tirzepatide is safe and has a tolerable AE profile and is expected to play a huge role in the management of T2DM, insulin resistance, and weight loss soon," they concluded.

Reference:

Rahul Mishra, Rishi Raj, Ghada Elshimy, Isain Zapata, Lakshmi Kannan, Priyanka Majety, Dinesh Edem, Ricardo Correa, Adverse Events Related to Tirzepatide, Journal of the Endocrine Society, Volume 7, Issue 4, April 2023, bvad016, https://doi.org/10.1210/jendso/bvad016