Comparation of fixed‐ratio (IDegLira and iGlarLixi) versus free combination of basal insulin and glucagon‐like peptide‐1 receptor agonist for uncontrolled type 2 diabetes: A systematic review and network meta‐analysis

Abstract Objective This study aimed to evaluate the safety and efficacy of the fixed‐ratio combination (FRC) and free combination of basal insulin and glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) in patients with type 2 diabetes mellitus (T2DM). Methods PubMed, Web of Science, Embase, The Cochrane Library, and four Chinese databases were searched for relevant studies from inception to April 13, 2023. Phase III clinical trials involving FRC or free combination in patients with uncontrolled T2DM were included. A network meta‐analysis (NMA) was used to evaluate the effects of FRC and free combination. The Cochrane Collaboration's tool was used to evaluate the risk‐of‐bias. The primary outcomes were changes in hemoglobin A1c (HbA1c), body weight, and incident hypoglycemia. Secondary outcomes included changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). This study was registered with PROSPERO (CRD42023409585). Results Forty‐two trials with 23,619 patients were included in the NMA, and treatments were categorized as FRC, free combination and NOINSGLP (neither FRC nor free combination). The forest plots revealed comparable HbA1c control (mean difference (MD) = 0.07%, 95% confidence interval (CI): –0.17 to –0.30) between free combination and FRC. However, there were significant differences in the body weight (MD = –2.06 kg; 95% CI: –3.34 to –0.77), SBP (MD = –1.22 mmHg; 95% CI: –2.41 to –0.04), and DBP (MD = –1.09 mmHg; 95% CI: –1.94 to –0.24) between the two groups. Conclusions In patients with uncontrolled T2DM, the safety and efficacy of FRC and free combination therapy were comparable. The use of FRC is justifiable in patients requiring free combination.