A previous post-hoc analysis of the 26-week onset 2 trial indicated that with insulin glargine the effect of fast-acting insulin aspart (FA) vs. insulin aspart (IAsp) on PPG increment (meal test) was larger for subjects on high bolus insulin doses in bolus-naïve adults with T2D (duration ≥6 mo). This post-hoc analysis of the 16-week onset 9 trial aimed to confirm this and explore efficacy and safety of FA vs. IAsp, both with insulin degludec, in bolus-experienced adults with T2D (duration ≥10 yrs) by insulin requirement. Participants were divided by meal test bolus dose at baseline: ≤10 U (n=303), 10-20 U (n=518) or >20 U (n=270). Baseline characteristics were similar across subgroups; except for BMI and daily insulin dose, which increased with meal test dose (Table). Change from baseline in HbA1c 16 weeks post randomization was similar for FA vs. IAsp across subgroups. There was a trend in favor of FA vs. IAsp for change from baseline in PPG increments (meal test), but treatment differences did not depend on subgroup. There was a trend towards lower rates of severe or blood glucose-confirmed hypoglycemia with higher insulin doses at meal test, with a benefit for FA vs. IAsp in the >20 U subgroup. Treatment difference (FA vs. IAsp) in change from baseline in PPG increments was unaffected by bolus insulin dose; however hypoglycemia risk may be lower with FA vs. IAsp in adults with long-standing T2D and high bolus insulin requirements.
W. Lane: Research Support; Self; AstraZeneca, Gilead, Mylan, Sanofi, Tolerion, vTv. Other Relationship; Self; Dexcom, Insulet, Novo Nordisk. M. Ekelund: Employee; Self; Novo Nordisk. Stock/Shareholder; Self; Novo Nordisk. Stock/Shareholder; Spouse/Partner; Novo Nordisk. Ó. Thórisdóttir: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. E. Jódar: Other Relationship; Self; Elli Lilly & Co, Novo Nordisk, MSD, Lilly, Janssen, Pfizer, AstraZeneca, Sanofi, UCB, Amgen, FAES, Shire, Mundipharma, Novartis. A. Oviedo: None. N. Rathor: Employee; Self; Novo Nordisk. P. Senior: Research Support; Self; Allergan, Novo Nordisk. G. Sesti: Advisory Panel; Self; Servier, Mylan, Novo Nordisk, Boehringer Ingelheim, Lilly, AstraZeneca, MSD, Sanofi, Amgem, Novartis, GSK. Speaker’s Bureau; Self; Novo Nordisk, Servier, MSD, Boehringer Ingelheim, Lilly, AstraZeneca, L-Nutra, Theras, Sanofi, Mundipharma, Omikron, Novartis. E. Franek: Advisory Panel; Self; Novartis AG. Speaker’s Bureau; Self; AstraZeneca, Bioton, Eli Lilly and Company. Other Relationship; Self; Boehringer Ingelheim, Novo Nordisk.