Insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi) compared to premix or addition of meal-time insulin to basal insulin in people with type 2 diabetes: A systematic review and Bayesian network meta-analysis.

AIMS In people with type 2 diabetes (T2D) inadequately controlled on basal insulin (BI), advancement to other insulin regimens is recommended. A fixed-ratio combination of insulin glargine 100U/mL and lixisenatide, iGlarLixi, is a marketed treatment option. However, head-to-head studies against other intensification and alternative therapeutic regimens are not available. Efficacy and safety of iGlarLixi was assessed relative to other insulin options through network meta-analysis. METHODS A systematic literature search identified randomized controlled trials (RCTs) comparing iGlarLixi, premix insulin, or BI in combination with meal-time insulin, in people inadequately controlled with BI. Eligible RCTs were compared using Bayesian network meta-analysis. RESULTS Eight RCTs, some open-label, involving 3,538 participants, with a study duration of 24-30 weeks were included. The estimated difference in HbA1c reduction with iGlarLixi compared to premix insulin was -0.50 %-units (95% credible interval: -0.93, -0.06) with 98% probability of iGlarLixi being superior to premix. Estimates for iGlarLixi vs meal-time+basal insulin (three times daily meal-time insulin + basal) and basal-plus (once per day meal-time insulin + BI) were -0.35 (-0.89, +0.13) %-units and -0.68 (-1.18, -0.17) %-units with probabilities of real-difference of 94% and 99%. Safety outcome analysis suggested iGlarLixi had lower rates of both confirmed and documented symptomatic hypoglycaemia compared to premix insulin (probabilities 85% and 93%), and lower weight gain (probability 98%). CONCLUSIONS iGlarLixi demonstrated similar or improved efficacy and safety versus other intensification choices from BI included in this study, providing a clinically relevant treatment option in people with T2D not well controlled on BI This article is protected by copyright. All rights reserved.