Abstract
OBJECTIVE: IDegLira is a novel, fixed-ratio combination of the long-acting basal insulin, insulin degludec, and the long-acting glucagon-like peptide-1 analog liraglutide. We studied the effect of IDegLira versus its components on postprandial glucose (PPG) in type 2 diabetes. METHODS: In this substudy, 260 (15.6%) of the original 1663 patients with inadequate glycemic control participating in a 26-week, open-label trial (DUAL I) were randomized 2:1:1 to once-daily IDegLira, insulin degludec or liraglutide. Continuous glucose monitoring (CGM) for 72 hours and a meal test were performed. RESULTS: At week 26, IDegLira produced a significantly greater decrease from baseline in mean PPG increment (normalized iAUC0-4h) than insulin degludec (estimated treatment difference [ETD] -12.79 mg/dl [95% CI: -21.08; -4.68], P = .0023) and a similar magnitude of decrease as liraglutide (ETD -1.62 mg/dl [95% CI: -10.09; 6.67], P = .70). CGM indicated a greater reduction in change from baseline in PPG increment (iAUC0-4h) for IDegLira versus insulin degludec over all 3 main meals (ETD -6.13 mg/dl [95% CI: -10.27, -1.98], P = .0047) and similar reductions versus liraglutide (ETD -1.80 mg/dl [95% CI: -2.52, 5.95], P = .4122). Insulin secretion ratio and static index were greater for IDegLira versus insulin degludec (P = .048 and P = .006, respectively) and similar to liraglutide (P = .45 and P = .895, respectively). CONCLUSIONS: Once-daily IDegLira provides significantly better PPG control following a mixed meal test than insulin degludec. The improvement is at least partially explained by higher endogenous insulin secretion and improved beta cell function with IDegLira. The benefits of liraglutide on PPG control are maintained across all main meals in the combination.