Real-World Data Reveals Tirzepatide's Risks and Benefits

Tirzepatide is associated with a lower risk of pancreatitis and diabetes-related vision loss compared to other drugs in the same class, a real-world data suggests.

Tirzepatide, sold under the names Mounjaro and Zepbound, is a type of glucagon-like peptide-1 receptor agonist (GLP-1s), a class of drugs for treating type 2 diabetes and obesity. They work by regulating blood glucose levels, reducing appetite, and slowing gastric emptying.

With their increasing use — one in eight Americans report ever taking GLP-1s — there is a growing concern over adverse events. Research has associated some types of GLP-1s with an increased risk of pancreatitis, stomach paralysis, and bowel obstruction.

However, real-world evidence from the FDA Adverse Event Reporting System (FAERS) database, presented at this year's Annual Meeting of The European Association for the Study of Diabetes (EASD) and published in The Journal of Endocrinological Investigation, suggests a reassuring safety profile for tirzepatide.

Moreover, tirzepatide has shown greater weight loss, which is crucial for reducing the risk of developing type 2 diabetes and improving health outcomes in those living with diabetes or obesity.

A 30-times higher risk of burping

In the study, researchers mined the FAERS post-marketing surveillance database, which includes reports from manufacturers, patients, and health professionals.

They retrieved reports of adverse events for tirzepatide related to gastrointestinal disorders, pancreatitis, gallbladder inflammation, gallstones, diabetic retinopathy, and thyroid neoplasms. A total of 7,460 reports, referring to 286 selected adverse events, were analyzed, of which 22 showed a disproportionality signal.

Adverse event occurrence with tirzepatide was also compared to other diabetes treatments, including insulin, SGLT-2 inhibitors, metformin, and GLP-1s.

Reports of burping were 30 times more likely with tirzepatide compared to other drugs. Additionally, nausea, indigestion, constipation, and pancreatitis were four times more likely to be reported with tirzepatide compared to all other drugs.

However, tirzepatide was associated with a similar risk of gastrointestinal adverse events as other GLP-1s, except for a lower risk of nausea and a higher risk of constipation.

Concern over thyroid cancer risk

While tirzepatide was associated with a greater risk of pancreatitis compared to insulin, the risk was lower in comparison to other GLP-1s.

Based on three cases of medullary thyroid cancer reported to FAERS, tirzepatide was associated with a similar risk for the condition as other GLP-1s and SGLT-2 inhibitors, and a greater risk compared to insulin.

The label of Mounjaro and other GLP-1s carries a warning that the drugs caused thyroid cancer in rats. However, an investigation by the European Medicines Agency didn't find any evidence that these medications cause thyroid cancer in humans. A recent study also concluded that the treatment with GLP-1s doesn't significantly increase the risk for the condition.

As for diabetic retinopathy, tirzepatide showed a similar risk to SGLT-2 inhibitors and a consistently lower risk compared with GLP-1ss and insulin. However, the findings are based on 12 reports of diabetic retinopathy only.

The authors note that the findings should be interpreted with caution, as the study is limited by its observational nature and the relatively short experience with tirzepatide.

Tirzepatide may have a better safety profile compared to other GLP-1s, but it still can cause adverse events that require immediate medical care.