Indirect comparison of efficacy and safety of insulin glargine/lixisenatide and insulin degludec/insulin aspart in type 2 diabetes patients not controlled on basal insulin

Abstract

Background: Fixed-dose combinations of insulin glargine/lixisenatide (IGlarLixi) or insulin degludec/insulin aspart (IDegAsp) constitute treatment intensification in type 2 diabetes mellitus (T2D). Objectives: Compare efficacy and safety of IGlarLixi and IDegAsp (as intensification from basal insulin), by indirect comparison of phase III trials, in the absence of head-to-head trials. Study eligibility criteria: Studies comparing treatment intensification by once-daily IDegAsp or IGlarLixi to basal insulin. Data were extracted from two trials (BOOST: Intensify-Basal and LixiLan-L) retained for analysis. Synthesis methods: Treatments were compared in terms of estimated treatment difference (ETD) in glycated haemoglobin (HbA1c), fasting and postprandial plasma glucose (FPG and PPG) change from baseline; in addition to hypoglycaemia incidence and weight changes. Results: In a fixed-effect model examining HbA1c control, IGlarLixi was more effective than IDegAsp in reducing HbA1c (ETD 0.53%, P < 0.0001]), PPG (ETD 2.65%, P < 0.0001), and body weight (ETD 1.73 kg, P < 0.0001). Patients on IGlarLixi were more likely to achieve HbA1c < 7% than patients on IDegAsp (odds ratio [OR] = 0.40, P < 0.0001), with lower incidence of hypoglycaemia (OR = 1.33, P < 0.001). Limitations: Limited number of studies; different baseline HbA1c and FPG. Conclusion: Once-daily IGlarLixi is more efficient than once-daily IDegAsp in controlling HbA1c and PPG and associates with greater weight loss and lower hypoglycaemia incidence.

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

“…Because of the absence of a Japanese IDegAsp prior insulin study and the small number of studies overall, we were not convinced of the merits of separate analyses of prior insulin versus no prior insulin, but a very recent publication selected the two international prior insulin studies we identified 3 , 16 and reported, by ITC, statistically significant HbA1c and bodyweight improvements of the same order we found, in addition to improvements in PPPG. 29 …”

“…Because of the absence of a Japanese IDegAsp prior insulin study and the small number of studies overall, we were not convinced of the merits of separate analyses of prior insulin versus no prior insulin, but a very recent publication selected the two international prior insulin studies we identified 3,16 and reported, by ITC, statistically significant HbA1c and bodyweight improvements of the same order we found, in addition to improvements in PPPG. 29 One issue might be that iGlar doses were capped in the iGlarLixi studies but not in the IDegAsp studies, thus possibly giving a comparator advantage to iGlarLixi. However, this issue has been investigated for some of the LixiLan studies by Schmider et al, who reported that uncapping the iGlar dose would not have led to significant improvements in fasting self-monitored blood glucose or HbA1c.…”