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

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.