A systematic review of the safety of tirzepatide-a new dual GLP1 and GIP agonist - is its safety profile acceptable?

AimsTirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA). At present, there is no controversy over its effectiveness, but its safety. We conducted a systematic review to assess the safety of tirzepatide.MethodsWe searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) of tirzepatide from databases inception to August 28, 2022 and used the Cochrane Systematic Assessment Manual Risk of Bias Assessment Tool (version 5.1) and modified Jadad scale to assess risk of bias. The systematic review was conducted via Revman5.4.ResultsNine RCTs with a total of 9818 patients were included. The overall safety profile of tirzepatide is similar to GLP-1RAs, except for the hypoglycemia (tirzepatide 15mg, pooled RR=3.83, 95% CI [1.19- 12.30], P=0.02) and discontinuation (tirzepatide 10mg, pooled RR=1.75,95%CI[1.16-2.63], P=0.007 and 15mg, pooled RR=2.03, 95%CI [1.37-3.01], P=0.0004). It also showed that the dose escalation could not rise the occurrence rates of total, severe, gastrointestinal adverse events and hypoglycemia (P>0.05); Compared with 5mg, tirzepatide 10mg and 15mg were associated with more frequent nausea (P