OBJECTIVES: To compare the efficacy and safety of lixisenatide combined with basal insulin versus Insulin regimens for the treatment of patients with type 2 diabetes mellitus (T2DM) inadequately controlled by basal insulin.

METHODS: A systematic literature review was conducted in PubMed, Cochrane Library, CNKI, and WanFang database up to January 15, 2018. Randomized controlled trials (RCTs) that investigated lixisenatide combined with basal insulin, premixed insulin and basal insulin plus prandial insulin with the main meal (basal plus) or progressively covering all meals (basal-bolus) in the treatment of T2DM patients inadequately controlled by basal insulin for ≥24 weeks were identified. Taking the heterogeneity into account, network meta-analysis (NMA) using a random effect model was applied to calculate the relative risk (RR) or standardized mean difference (SMD) with 95% credibility interval (95%Crl) within a Bayesian framework.

RESULTS: Eight RCTs involving 3,584 patients were included. NMA showed that lixisenatide combined with basal insulin had a similar reduction in HbA1c compared with basal plus (SMD=-0.23%, 95%Crl: -0.61% to 0.15%), premixed insulin (SMD=-0.12%, 95%Crl: -0.50% to 0.25%) and basal bolus (SMD=0.09%, 95%Crl: -0.31% to 0.49%). There are significant differences in the change of body weight in favor of lixisenatide combined with basal insulin compared with basal plus (SMD=-1.73kg, 95%Crl: -2.37 to -1.09kg), premixed insulin (SMD=-2.28kg, 95%Crl: -2.91 to -1.64kg), and basal bolus (SMD=-2.35kg, 95%Crl: -3.05 to -1.65kg). The relative risk of symptomatic hypoglycemia of lixisenatide combined with basal insulin was significantly lower compared with premixed insulin (RR=0.60, 95%Crl: 0.46 to 0.93) and basal bolus (RR=0.60, 95%Crl: 0.43 to 0.83), and was no significant difference compared with basal plus (RR=0.75, 95%Crl: 0.55 to 1.04).

CONCLUSIONS: Lixisenatide combined with basal insulin showed similar HbA1c reduction to premixed insulin, basal plus and basal bolus, accompanied by a significantly lower risk of hypoglycemia and a greater body weight loss.