Insulin degludec/liraglutide has proven to be superior to insulin glargine in hemoglobin A1c reduction, risk of hypoglycemia, and weight reduction in the DUAL V study. This result of the open-label DUAL V trial was reported at the Annual Meeting of the European Association for the Study of Diabetes 2015.
Dr. Ildiko Lingvay, of the University of Texas Southwestern Medical Center, Dallas, explained that the 26-week, open-label DUAL V trial compared the efficacy and safety of insulin degludec/liraglutide vs insulin glargine in subjects with type 2 diabetes uncontrolled on insulin glargine (20 ‒ 50 U) and metformin.
Adults (n=557, hemoglobin A1c 7‒10%) were randomized to either once-daily insulin degludec/liraglutide or continued insulin glargine uptitration, both plus metformin.
Initial doses were 16 dose steps (16 U insulin degludec + 0.6 mg liraglutide, maximum 50 dose steps) for insulin degludec/liraglutide and a mean pretrial dose for insulin glargine of 32 U (no maximum). The fasting self-measured blood glucose titration target was 4.0 ‒ 5.0 mmoL/L for both arms.
Mean hemoglobin A1c decreased from 8.4% to 6.6% with insulin degludec/liraglutide (change from baseline ‒1.81% ± 1.08%) and from 8.2 to 7.1% with insulin glargine (change from baseline ‒1.13% ± 0.98%); estimated treatment difference between insulin degludec/liraglutide and insulin glargine, ‒0.59 [‒0.74; ‒0.45], P < .001.
Mean fasting plasma glucose decreased similarly in both arms from 8.9 to 6.1 mmoL/L with a change from baseline of ‒2.83 ± 2.80 mmoL/L with insulin degludec/liraglutide and ‒2.77 ± 3.02 mmoL/L with insulin glargine. The estimated treatment difference was not significant at ‒0.01 mmoL/L [‒0.35; 0.33].
Weight decreased from 88.3 to 86.9 kg with insulin degludec/liraglutide (change from baseline ‒1.4 ± 3.5 kg and increased from 87.3 to 89.1 kg with insulin glargine (change from baseline 1.8 ± 3.6 kg). The estimated treatment difference for weight change was ‒3.20 kg [‒3.77; ‒2.64], P < .001.
Significantly more subjects achieved the American Diabetes Association hemoglobin A1c target and prespecified composite endpoints with insulin degludec/liraglutide vs insulin glargine: hemoglobin A1c <7%, 71.6 vs 47.0%, estimated odds ratio 3.45 [2.36; 5.05]; hemoglobin A1c <7% without hypoglycemia, 54.3 vs 29.4%, estimated odds ratio 3.24 [2.24; 4.70]; hemoglobin A1c <7% without hypoglycemia and no weight gain, 38.8 vs 12.2%, estimated odds ratio 5.53 [3.49; 8.77], respectively, all P < .001.
Insulin degludec/liraglutide was insulin sparing: the mean 26-week dose of insulin degludec/liraglutide was 41 dose steps vs 66 U of insulin glargine (P < .001).
Dr. Lingvay concluded that insulin degludec/liraglutide proved to be superior to insulin glargine in reducing hemoglobin A1c, lowering hypoglycemia risk, weight reduction, and decreasing insulin dose requirements.
Due to its greater reduction in hemoglobin A1c and lower rate of hypoglycemia, insulin degludec/liraglutide offers meaningful clinical advantages over insulin glargine in intensifying therapy in subjects with type 2 diabetes uncontrolled on insulin glargine.