Effect of the Dual Glucose‐Dependent Insulinotropic Peptide/Gulcagon‐like Peptide 1 Receptor Agonist Tirzepatide on Lipid Profile and Waist Circumference: A Systematic Review and Meta‐analysis

Purpose Tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide 1 receptor agonist, has been approved by the US Food and Drug Administration for the treatment of type 2 diabetes. The purpose of this meta-analysis is to evaluate the impact of tirzepatide on lipid profile and waist circumference (WC), both of which are risk factors of cardiovascular diseases. Methods The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were systematically searched for articles published from database inception to July 31, 2022. This meta-analysis included 7 randomized controlled trials with a minimum duration of 12 weeks that compared tirzepatide with placebo or other antidiabetic medications. The random-effects model was used to estimate mean differences in lipid profile and WC from baseline. The Cochrane risk-of-bias tool for randomized trials, version 2 was used to assess the outcome's risk of bias. We evaluated the evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Findings A total of 8 articles from 7 trials with 7151 participants were included. All 3 eligible maintenance doses of tirzepatide (5, 10, and 15 mg once a week) were effective in increasing total cholesterol (TC) (P < 0.05), HDL-C (P < 0.05), VLDL-C (P < 0.01), triglyceride (TG) (P < 0.01), and WC (P < 0.01) changes from baseline compared with control agents including placebo, semaglutide, dulaglutide, and degludec. Although the evidence for VLDL-C and TGs by GRADE were high or moderate, the evidences for TC, HDL-C, and WC were low or moderate. Only 5mg once-weekly tirzepatide (P < 0.05), not 10 or 15 mg, could induce significant alteration in LDL-C before sensitivity analysis. The evidence by GRADE was moderate. Implications Tirzepatide had superiority over placebo or other antidiabetic agents in controlling lipid and WC levels. However, the levels of evidence by GRADE varied greatly across different outcome indicators. Limitations of the study include evaluating secondary outcomes of original trials for the meta-analyses, not assessing the effect of baseline lipid-lowering therapy on lipid levels, and not exploring the bias induced by glycemic improvement and weight loss.