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.

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 1.73kg, 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.