IDegLira improves CV risk markers in patients with T2D uncontrolled on basal insulin (DUAl V/ VII)

Background and aims: the efficacy and safety of insulin degludec/liraglutide (IDegLira) has been demonstrated in patients with type 2 diabetes (T2D) uncontrolled on basal insulin, with superior HbA1c reductions vs basal insulin. The CV benefit of liraglutide vs placebo has also been shown in the LEADER CV outcomes trial. This post hoc analysis examined the effect of IDegLira vs insulin degludec (IDeg; DUAL II) and vs insulin glargine U100 (IGlar U100; DUAL V), both with metformin (Met) for 26 weeks, on CV risk markers. Materials and methods: DUAL II was a 26-week, randomised, double-blind, treat-to target trial; 413 patients with T2D (HbA1c 7.5-10%) on basal insulin (20-40 U) and Met (±sulfonylurea/glinides) were randomised 1:1 to once-daily (OD) IDegLira or IDeg. DUAL V was a 26-week, randomised, open-label, treat-to-target trial; 557 patients with T2D (HbA1c 7-10%) treated with IGlar U100 and Met were randomised 1:1 to OD IDegLira or IGlar U100. Results: in both trials, there was a greater decrease in systolic blood pressure with IDegLira and small but statistically significant increases in mean heart rate were observed with IDegLira vs comparators (both p<0.001). IDegLira was associated with weight loss vs weight gain with comparators (estimated treatment difference [ETD] -2.5kg [-3.2; -1.8]95%CI p<0.0001 and ETD: -3.2kg [-3.8; -2.6]95%CI p<0.05 for DUAL II and DUAL V respectively). Lipid profile improved with IDegLira in both trials; total cholesterol and LDL-cholesterol were significantly lower vs comparators. In DUAL II, Apolipoprotein-B and Brain Natriuretic Peptide (BNP) were significantly lower with IDegLira vs IDeg (estimated treatment ratio [ETR] 0.92 [0.88; 0.95]95%CI p<0.0001 and 0.66 [0.55; 0.79]95%CI p<0.0001 respectively), while high-sensitivity C-reactive protein (hsCRP) was similar after 26 weeks of treatment (ETR 0.90 [0.78; 1.04]95%CI p = NS). Conclusion: IDegLira is associated with a general improvement in CV risk markers vs basal insulin therapy after 26 weeks of treatment, which is likely attributable to the liraglutide component.