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. (C) 2020 The Author. Published by Elsevier Ltd on behalf of Primary Care Diabetes Europe.