Tirzepatide tied to lower odds for diabetic retinopathy, pancreatitis than GLP-1s
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Key takeaways:
- The odds of gastrointestinal adverse events are similar among people using tirzepatide and those using GLP-1 receptor agonists.
- Tirzepatide users were less likely to report pancreatitis than GLP-1 users.
Tirzepatide is associated with similar odds for gastrointestinal adverse events and a lower likelihood for diabetic retinopathy and pancreatitis compared with GLP-1 receptor agonists, according to a presenter.
“Our analysis of the FDA Adverse Events Reporting System database suggests that, despite its unprecedented glucose and weight lowering efficacy, tirzepatide has a similar, if not better, safety profile compared to the already widely used GLP-1 receptor agonists in terms of gastrointestinal adverse events, pancreatobiliary disorders, diabetic retinopathy and medullary thyroid cancer,” Irene Caruso, MD, research fellow in the department of precision and regenerative medication and ionian area at the University of Bari Aldo Moro in Italy, told Healio.
In findings presented at the European Association for the Study of Diabetes and simultaneously published in the Journal of Endocrinological Investigation, researchers obtained reports of gastrointestinal adverse events, pancreatitis, cholecystitis, cholelithiasis, diabetes retinopathy and thyroid neoplasm for people using tirzepatide (Mounjaro/Zepbound, Eli Lilly), a GLP-1/GIP receptor agonist, from the FDA Adverse Events Reporting System database. Adverse events for tirzepatide users were compared with events among people using all other drugs, including GLP-1 receptor agonists, SGLT2 inhibitors, metformin and insulin.
There were 20,409 reports related to 1,432 adverse events with tirzepatide, with 38% of the events related to injection-site injuries or incorrect dose administration.
Compared with all other drugs, tirzepatide was associated with a higher likelihood for multiple gastrointestinal adverse events, pancreatitis, biliary colic, diabetic retinopathy and medullary thyroid cancer. The odds for gastrointestinal events and medullary thyroid cancer with tirzepatide were similar to other GLP-1 receptor agonists, and tirzepatide was tied to lower odds for diabetic retinopathy and pancreatitis than GLP-1s.
“We found that tirzepatide had a reduced risk of nausea, vomiting and diarrhea vs. GLP-1 receptor agonists, while the SURPASS-2 trial comparing semaglutide [Ozempic/Wegovy, Novo Nordisk] and tirzepatide did not show any differences,” Caruso said. “However, preclinical studies showed that GIP agonism might activate GABAergic neurons in the brainstem, which in turn will hinder GLP-1-induced malaise, aligning with our results.”
People using tirzepatide were more likely to experience gastrointestinal events compared with those using SGLT2 inhibitors and insulin. Pancreatitis and biliary colic were more common with tirzepatide vs. insulin, but no difference in those events was seen between tirzepatide and SGLT2 inhibitors. No difference in diabetic retinopathy or medullary thyroid cancer odds were observed between tirzepatide and SGLT2 inhibitor users. Tirzepatide was tied to lower odds for diabetic retinopathy and higher odds for medullary thyroid cancer compared with insulin.
Caruso noted the FDA Adverse Events Reporting System has limitations, including incomplete information and biases leading to underreporting or overreporting. Additionally, Caruso said the study only included data through the third quarter of 2023.
“Rigorous observational studies with a longer follow-up and the possibility to match cohorts with techniques such as propensity-score matching are required to overcome these limitations,” Caruso said. “Also, we found a reduced risk of gallbladder and biliary-related disorders with tirzepatide vs. GLP-1 receptor agonists. Mechanistic studies might be useful to investigate the role of GIP and tirzepatide on gallbladder and biliary function.”
Reference:
Caruso I, et al. J Endocrinol Invest. 2024;doi:10.1007/s40618-024-02441-z.
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Caruso I, et al. P735. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 9-13, 2024; Madrid, Spain.
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