Celebrities have often mentioned on broadcasts that they received obesity medication injections and lost weight, but they experienced nausea. It is possible that changing the medication could have prevented such issues. Recent research results show that new-generation obesity medications have fewer side effects than those currently in widespread use.
A research team from the University of Pennsylvania announced on the 19th that animal experiments have demonstrated that tirzepatide has fewer gastrointestinal side effects than semaglutide. The research findings were published in the international journal "Science Advances" on the same day.
Tirzepatide is an ingredient in the obesity drug "Zepbound" produced by the American pharmaceutical company Eli Lilly, while semaglutide is found in Denmark's Novo Nordisk's "Wegovy." Recently, Zepbound's superiority in weight loss effects has been confirmed, and with this new finding of fewer side effects, attention is focused on how it may change the landscape of the obesity medication market.
Both Zepbound and Wegovy are obesity treatments within the glucagon-like peptide (GLP)-1 class. These drugs mimic the hormone GLP-1, secreted in the small intestine after meals, which promotes the secretion of insulin, lowering blood sugar, while suppressing glucagon that raises blood sugar, thereby enhancing feelings of fullness.
GLP-1 class obesity medications have shown double-digit weight loss effects and have been sold like hotcakes worldwide. However, as the use of these medications increased, various side effects also emerged. The typical side effects include gastrointestinal issues such as nausea and vomiting.
The research team conducted experiments by administering semaglutide and tirzepatide to rodents. The drugs were repeatedly administered at a certain dosage through subcutaneous injections or oral administration. Overall, the results showed no significant difference in weight loss effects.
However, the side effects showed clear differences. The researchers examined the kaolin intake level to confirm nausea in the experimental animals. Kaolin is a clay mineral used in cosmetics and pottery and can induce nausea when ingested. Animals administered semaglutide had higher kaolin intake levels than those in the tirzepatide group.
The drug that mimics GLP-1 contains kaolin. The researchers noted that kaolin was detected in high amounts in animals administered semaglutide, but almost none was found in the tirzepatide group, which used a gastric inhibitory peptide (GIP) agonist.
In fact, many patients who took Wegovy discontinued it due to nausea. In previous research, 44.2% of patients who took semaglutide reported experiencing nausea, while 24.8% complained of vomiting. Most of these side effects occurred within 20 weeks of starting the medication.
Zepbound has been known to have fewer side effects such as nausea or vomiting compared to Wegovy. Tirzepatide acts not only on GLP-1 but also on GIP. GIP breaks down fat cells and reduces nausea.
The research team stated, "The GIP receptors of tirzepatide induce anti-nausea effects, suppressing nausea and vomiting, while reducing side effects like nausea, vomiting, and aversion reactions caused by GLP-1 receptor activation, while maintaining weight loss and blood sugar improvement effects."
The University of Pennsylvania research team indicated, "This study allowed for a systematic analysis of the side effects of the two medications that are currently the most effective treatments for obesity and type 2 diabetes," and it is a study aimed at designing drugs that reduce gastrointestinal side effects and maximize therapeutic effects.
This research is expected to impact not only academia but also the market. Wegovy received U.S. Food and Drug Administration (FDA) approval and was launched in June 2021, and Zepbound entered the market in December 2023 as a new contender. Consequently, Wegovy captured over 70% of the market quickly, with Zepbound following behind.
Recently, the dynamics of the obesity medication market are shifting. This is because Zepbound's superiority has been confirmed in both weight loss effects and side effects. Last month, a research team from Weill Cornell Medicine announced in the international journal "New England Journal of Medicine" that Zepbound had greater weight loss effects compared to Wegovy in a clinical trial that directly compared the two drugs. Patients administered Zepbound experienced an average weight loss of 20.2%, while those on Wegovy lost 13.7%.
As it has now been confirmed that Zepbound has fewer side effects than Wegovy, it has gained a more advantageous position in the market. Initially, Eli Lilly struggled to meet demand due to insufficient production facilities for the obesity medication, but this issue has recently been resolved. With the drug's efficacy confirmed and supply issues addressed, there are projections that the top position in the obesity medication market may change.
References
Science Advances (2025), DOI: https://doi.org/10.1126/sciadv.adu1589
New England Journal of Medicine (2025), DOI: https://doi.org/10.1056/NEJMoa2416394