Gastrointestinal adverse events of tirzepatide in the treatment of type 2 diabetes mellitus: A meta-analysis and trials sequential analysis

Background: Tirzepatide (TZP) is a novel drug for type 2 diabetes mellitus (T2DM), but the gastrointestinal (GI) adverse events (AEs) is a limiting factor in clinical application. Therefore, this study systematically evaluated the GI AEs of TZP for T2DM. Methods: Clinical trials of TZP for T2DM were retrieved from eight databases published only from the establishment of the database to February 2023. Revman5.3 and TSA0.9.5.10 Beta were used for meta-analysis and trials sequential analysis (TSA). Results: Meta-analysis showed that compared with placebo, total GI AEs, nausea, decreased appetite, constipation and vomiting were significantly higher in all dose groups of TZP (P < .05), while abdominal pain and abdominal distension were comparable (P > .05). TSA showed that the differences in total GI AEs, nausea, decreased appetite and constipation were conclusive. Compared with insulin, nausea, diarrhea, vomiting and decreased appetite were significantly increased in all doses of TZP (P < .05), and dyspepsia was significantly increased with TZP 15 mg (P < .05). TSA showed that these differences were all conclusive. Compared with GLP-1 RA, decreased appetite was significantly higher with TZP 5 mg, total GI AEs, decreased appetite and diarrhea were significantly higher with TZP 10 mg (P < .05), while nausea, vomiting, dyspepsia and constipation were significantly different in all dose groups, abdominal pain were not significantly different (P < .05) and TSA showed no conclusive results in this group. Conclusion: The GI AEs of TZP were significantly higher than those of placebo and insulin, but comparable to GLP-1 RA. Nausea, diarrhea and decreased appetite are very common GI AEs of TZP, and the incidence is positively correlated with dose. GI AEs of TZP decrease gradually over time, so long-term steady medication may be expected to reduce GI AEs.