Real-World Analysis of Tirzepatide Reveals Comparable Safety Profile to GLP-1 Receptor Agonists

The researchers revealed that TZP was linked to a higher risk of certain adverse events. However, its overall safety profile was comparable to that of GLP-1 receptor agonists, with no elevated risk for pancreatic-biliary adverse events, diabetic retinopathy, or medullary thyroid cancer.

"Tirzepatide is linked to similar rates of gastrointestinal adverse events and shows a reduced likelihood of diabetic retinopathy and pancreatitis compared to GLP-1 receptor agonists," the researchers reported in the Journal of Endocrinological Investigation. 

Randomized controlled trials of tirzepatide have demonstrated remarkable efficacy in reducing glucose levels and body weight in individuals with type 2 diabetes and/or obesity, while its safety profile is comparable to that of glucagon-like peptide-1 receptor agonists (GLP-1RA), primarily featuring gastrointestinal (GI) adverse events. The trials also addressed concerns related to diabetic retinopathy, pancreato-biliary disorders, and medullary thyroid cancer.

Against the above background, F. Giorgino, University of Bari Aldo Moro, Bari, Italy, and colleagues aimed to examine whether similar safety concerns were reported in the FAERS post-marketing surveillance database.

For this purpose, the researchers utilized OpenVigil 2.1-MedDRA-v24 and AERSMine (data from Q1 2004 to Q3 2023) to query the FAERS database. They investigated reports of gastrointestinal adverse events (AE), diabetic retinopathy, pancreato-biliary disorders, and medullary thyroid cancer. The analysis was refined based on factors such as age, gender, and designation as the primary suspect. The occurrence of AEs with tirzepatide (TZP) was then compared to those associated with insulin, sodium-glucose cotransporter-2 inhibitors, metformin, and GLP-1 receptor agonists.

The following were the key findings of the study:

• Disproportionate reporting of GI [i.e., nausea (ROR 4.01] and pancreato-biliary disorders [i.e., pancreatitis (ROR 3.63], diabetic retinopathy (ROR 4.14), and medullary thyroid cancer (ROR 13.67) were detected.
• TZP exhibited a similar risk of GI AE and medullary thyroid cancer and a lower risk of most pancreato-biliary AE and diabetic retinopathy vs. GLP-1RA.

"Real-world evidence from the FAERS database shows that tirzepatide has a reassuring safety profile. Despite its notable efficacy, TZP demonstrates comparable gastrointestinal tolerability to the widely used GLP-1 receptor agonists and does not show an increased risk of pancreatitis, diabetic retinopathy, or medullary thyroid cancer," the researchers concluded.

The researchers noted that the FAERS database has limitations, including the lack of established cause-effect relationships for adverse events (AEs) and potential duplicates or incomplete reports. Additionally, missing details, varied reporting sources, and difficulties distinguishing drug formulations may affect data. The analysis also covers only the first 16 months of tirzepatide availability in the U.S.

Reference:

Caruso, I., Di Gioia, L., Di Molfetta, S. et al. The real-world safety profile of tirzepatide: pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02441-z