SEMAGLUTIDE and tirzepatide have emerged as promising treatments for weight management in adults without diabetes. These glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated significant efficacy in promoting weight loss and improving metabolic health. However, concerns have been raised regarding their safety, particularly the risk of gastrointestinal (GI) adverse events. A recent study evaluated the GI safety profile of both semaglutide and tirzepatide, observing a notable increase in the incidence of GI issues with both drugs, with tirzepatide presenting a higher risk than semaglutide.
Researchers analysed data from 13 RCTs that investigated the effects of semaglutide and tirzepatide on GI, hepatic, pancreatic, and biliary outcomes. In total, 26,894 participants with obesity but without diabetes were included. The studies provided information on adverse events such as nausea, vomiting, diarrhoea, constipation, and more severe GI disorders. The analysis compared the frequency of these adverse events in patients treated with either semaglutide or tirzepatide against control groups receiving placebos. Statistical measures, including risk ratios and confidence intervals, were used to assess the relative risks of GI complications associated with each medication.
The results revealed that GI adverse events were significantly more common in both the semaglutide and tirzepatide groups compared to the control groups. Specifically, 30.81% of participants receiving semaglutide experienced GI issues, while only 12.7% in the control group did. For tirzepatide, 79.8% of participants experienced GI events, a figure notably higher than the 25% observed in the control group. Semaglutide also increased the risk of gallbladder-related disorders, particularly cholelithiasis, by over 2.5 times. However, tirzepatide did not show a significant risk for biliary events. Neither medication was linked to a substantial increase in the incidence of hepatic or pancreatic disorders.
In conclusion, these findings highlight the importance of monitoring patients for potential GI side effects during treatment. However, the study’s limitations include the small number of available RCTs for tirzepatide and the lack of data on varying dosages. Future studies with larger populations and long-term follow-ups are necessary to gain a clearer understanding of the chronic effects of these medications and their safety profiles in clinical practice.
Reference
Safwan M et al. Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis. Ann Saudi Med. 2025;45(2):129-43
