Efficacy and Safety of GLP-1 Receptor Agonist Fixed-Dose Combinations or in Combination with Insulin in Patients with Poorly Controlled Type 2 Diabetes Mellitus:A Network Meta-Analysis
MA Jingzi
WANG Hongfei
NIU Yaping
WU Yunxiao
WU Shanshan
SUN Feng
Abstract：Objective To systematically evaluate the efficacy and safety of GLP-1 receptor agonist(GLP-1RA)fixed-dose combination or combination with insulin in patients with poorly controlled type 2 diabetes mellitus(T2DM).Methods Databases including PubMed,Embase,Cochrane Library,CNKI,Sinomed,VIP,and Wanfang were searched from inception to October 20,2024.Randomized controlled trials(RCT)involving T2DM patients with poor glycemic control treated with GLP-1RA fixed-dose combinations or GLP-1RA combined with insulin were strictly screened according to inclusion and exclusion criteria.Data were extracted and a network meta-analysis was conducted.Results A total of 40 RCTs involving 18 215 T2DM patients were included.Compared with GLP-1RA,Tirzepatide and Semaglutide combined with insulin showed superior effects in reducing HbA1c(WMD:-1.38,95%CI:-2.03--0.73;WMD:-1.30,95%CI:-2.02--0.58)and fasting plasma glucose(WMD:-3.30,95%CI:-4.17--2.43;WMD:-2.93,95%CI:-3.90--1.96).There was no significant difference in reducing 2-hour postprandial blood glucose(the 95%CI of WMD included 0).Tirzepatide demonstrated excellent weight loss effect(WMD:-6.23,95%CI:-9.45--3.01).No significant differences were observed in the risks of total adverse events,severe hypoglycemia,pancreatitis,or major adverse cardiovascular events(the 95%CI of OR included 1).Semaglutide combined with insulin had a higher risk of discontinuation due to adverse events(OR=6.76,95%CI:1.50-30.49).Conclusion In patients with poorly controlled T2DM,Tirzepatide provides the best glycemic control and weight management effects with high safety;Semaglutide combined with insulin offers excellent glycemic control and high safety,but carries a higher risk of discontinuation due to adverse events.Although GLP-1RA combined with insulin enhances glycemic control,the complexity of treatment requires careful consideration.This study provides evidence-based insights for clinical treatment strategies.
Keywords：type 2 diabetes mellitusGLP-1 receptor agonistnetwork meta-analysisefficacysafety
Publication Date：2026-02-20
Online Publishing Date：2026-03-16(First online date of this platform, not the publication date of the document)
Pages：9( 320-328 )