To the Editor A recent study reported that once-weekly treatment with tirzepatide can effectively lead to weight reduction. However, we have several concerns about this article. First, the effect of lifestyle in this study requires further exploration. Among patients receiving tirzepatide, there was a weight reduction of 11.3% to 15.1% compared with placebo. All patients underwent lifestyle intervention, and after 52 weeks of treatment, the placebo group had only a 2.3% reduction in body mass. Although the populations in the studies differed, the effect of lifestyle in the placebo group was significantly lower than in prior trials. Additionally, due to the Hawthorne effect, the tirzepatide group may have had improved uptake of the lifestyle intervention. Furthermore, data on the implementation of the lifestyle intervention in both the treatment and placebo groups were limited in this study. Second, a prior study reported a 20.9% weight reduction after 36 weeks of continuous tirzepatide use. However, patients who discontinued the drug experienced a 14% weight gain over the next 52 weeks despite undergoing lifestyle intervention. Does this imply that tirzepatide needs to be used long term to maintain weight control? If so, this raises concerns about the long-term safety of tirzepatide, including the risk of thyroid C-cell tumors mentioned in the black box warning. Third, during the tirzepatide dose escalation period, most participants reported at least 1 gastrointestinal adverse effect (eg, diarrhea, nausea, abdominal distension, vomiting, and gastroenteritis) and some patients discontinued the drug due to these gastrointestinal symptoms. Therefore, the suitability of tirzepatide for patients with preexisting gastrointestinal symptoms or conditions requires further investigation. Additionally, it is worth exploring whether certain medications that do not affect the efficacy of tirzepatide but can alleviate gastrointestinal symptoms could be used during the dose escalation period to improve patient comfort.
