Comparison of Efficacy and Safety of Commercially Available Fixed-Ratio Combinations of Insulin Degludec/Liraglutide and Insulin Glargine/Lixisenatide: A Network Meta-analysis

To compare the efficacy and safety of commercially available fixed ratio combinations (FRC) of glucagon-like peptide 1 receptor agonists (GLP-1RA) and basal insulins by a network meta-analysis (NMA) of randomised controlled trials (RCT) of type 2 diabetes patients.We report a systematic review and network meta-analyses of RCTs of type 2 diabetes patients randomized to FRCs or to their components for ≥24-weeks reported in PubMed or ClinicalTrials.gov until 28/FEB/2022. Primary outcome was attained HbA1c. Secondary outcomes included fasting plasma glucose, change in body weight, and incident hypoglycaemia. Treatment effects were estimated as mean differences and standard errors (MD; [SE]) or odds ratios (OR) with 95% confidence intervals (95%CI) using iGlarLixi as reference.We included 29 RCTs of the 1404 papers identified. No direct comparison between FRCs were found. After excluding some insulin capped trials to reach model consistency, both FRCs were more efficacious regarding HbA1c than their components, however no difference between FRCs were found (MD: -0.10 [SE: 0.10]%). The effect of IDegLira (-0.47 [0.24] mmol/l) and basal insulins was similar to that of iGlarLixi (ref.) on fasting glucose, while GLP-1RA had lower efficacy than iGlarLixi. Weight gain was lower with GLP-1RAs and IDegLira (-0.72 [0.32] kg) than iGlarLixi (ref.) and higher with basal insulins. Incident hypoglycemia (based on different definitions) was least frequent with GLP-1RAs followed by IDegLira (OR 0.78 95%CI 0.39-1.57), iGlarLixi (ref.) and basal insulins.Regarding HbA1c, both FRCs were more efficacious over their individual components with similar efficacies of the two FRCs.