Efficacy and safety of iGlarLixi versus IDegAsp: Results of a systematic literature review and indirect treatment comparison

Abstract

Aim: To assess the efficacy and safety of iGlarLixi, a fixed-ratio combination of basal insulin glargine 100 U/mL and lixisenatide (glucagon-like peptide-1 receptor agonist) versus IDegAsp, a co-formulation of basal insulin degludec 100 U/mL with rapid-acting insulin aspart. Materials and Methods: A systematic literature search of randomized controlled trials (RCTs) was performed. Outcomes from eligible RCTs were compared by an indirect treatment comparison using a Bayesian framework. Subanalyses of Japanese and international trials were performed. Results: Eight RCTs (duration 26-30 weeks) were included. Mean difference in HbA1c change with iGlarLixi exceeded that for IDegAsp: −0.64 (95% credible interval −1.01, −0.28) %-units (−7.0 [−11.0, −3.1] mmol/mol) for all trials, −0.39 (−0.55, −0.23) %-units (−4.3 [−6.0, −2.5] mmol/mol) for international, and −0.88 (−1.11, −0.64) %-units (−9.6 [−12.1, −7.0] mmol/mol) for Japanese trials. HbA1c target achievement (<7.0%-units [<53 mmol/mol]) was greater for iGlarLixi in all trials (odds ratio 2.50 [1.06, 5.56]) and Japanese trials (2.17 [1.27, 3.70]), but not in international trials (2.17 [0.42, 11.11]). Analyses suggesting differences in mean postmeal self-measured plasma glucose were significantly lower by 1.0-2.0 mmol/L (18-36 mg/dL) with iGlarLixi in all analyses. Bodyweight change was more favourable (1-2 kg) for iGlarLixi versus IDegAsp for all analyses (P < 0.05). Comparisons of hypoglycaemia were inconclusive owing to differences in definitions between studies. Adverse events were more frequent with iGlarLixi because of gastrointestinal intolerance. Conclusions: iGlarLixi appears to offer clinical benefit in glucose control and bodyweight change in people needing both basal and meal-time intervention.