A Randomized Trial Evaluating the Efficacy and Safety of Fast-Acting Insulin Aspart Compared With Insulin Aspart, Both in Combination With Insulin Degludec With or Without Metformin, in Adults With Type 2 Diabetes (ONSET 9)

Abstract

To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp), both with insulin degludec with or without metformin, in adults with type 2 diabetes not optimally controlled with a basalbolus regimen. RESEARCH DESIGN AND METHODS This multicenter, double-blind, treat-to-target trial randomized participants to faster aspart (n 5 546) or IAsp (n 5 545). All available information, regardless of treatment discontinuation or use of ancillary treatment, was used for evaluation of effect. RESULTS Noninferiority for the change from baseline in HbA 1c 16 weeks after randomization (primary end point) was confirmed for faster aspart versus IAsp (estimated treatment difference [ETD] 20.04% [95% CI 20.11; 0.03]; 20.39 mmol/mol [21.15; 0.37]; P < 0.001). Faster aspart was superior to IAsp for change from baseline in 1-h postprandial glucose (PPG) increment using a meal test (ETD 20.40 mmol/L [20.66; 20.14]; 27.23 mg/dL [211.92; 22.55]; P 5 0.001 for superiority). Change from baseline in self-measured 1-h PPG increment for the mean over all meals favored faster aspart (ETD 20.25 mmol/L [20.42; 20.09]); 24.58 mg/dL [27.59; 21.57]; P 5 0.003). The overall rate of treatment-emergent severe or blood glucose (BG)confirmed hypoglycemia was statistically significantly lower for faster aspart versus IAsp (estimated treatment ratio 0.81 [95% CI 0.68; 0.97]). CONCLUSIONS In combination with insulin degludec, faster aspart provided effective overall glycemic control, superior PPG control, and a lower rate of severe or BG-confirmed hypoglycemia versus IAsp in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen.

The continuing quest for better subcutaneously administered prandial insulins: a review of recent developments and potential clinical implications

“…This is conceptually similar to what was observed more than 20 years ago with the introduction of rapid‐insulin analogues . Trials in people with T2DM show a similar but lesser, yet statistically significant, reduction in the 1‐h PPG increment (mean decrease −0.40 to −0.59 mmol/L) compared with aspart . Despite reducing PPG levels in the trials reported, the overall glucose‐lowering ability of faster aspart compared with aspart (based on HbA1c levels) was comparable in T2DM or slightly better in T1DM .…”

“…Trials in people with T2DM show a similar but lesser, yet statistically significant, reduction in the 1‐h PPG increment (mean decrease −0.40 to −0.59 mmol/L) compared with aspart . Despite reducing PPG levels in the trials reported, the overall glucose‐lowering ability of faster aspart compared with aspart (based on HbA1c levels) was comparable in T2DM or slightly better in T1DM . SMPG profile data in several trials indicate that faster aspart has a minimal effect on reducing PPG after mixed meals.…”

“…Eight phase 3 trials have reported the efficacy and safety of faster aspart (Table ) . Seven phase 3 trials are evaluating the efficacy and safety of ultra‐rapid lispro versus lispro, with preliminary results for three of these trials reported as abstracts .…”

“…Two studies compared mealtime faster aspart with aspart in a basal‐bolus regimen in a 26‐week trial with insulin glargine 100 U/mL (glargine‐100) (Onset 2) and in a 16‐week trial with insulin degludec (Onset 9) . No significant difference in HbA1c at the end of treatment was observed in either trial (ETD −0.02% in Onset 2, −0.04% in Onset 9; both in favour of faster aspart).…”

Fast-Acting Insulin Aspart: A Review of its Pharmacokinetic and Pharmacodynamic Properties and the Clinical Consequences

“…Several faster aspart formulations with different combinations of niacinamide and zinc concentrations were tested in a clinical pharmacology trial, and, [16][17][18][19][20][21][22][23][24][25][26][27]. Moreover, phase III trials have investigated the efficacy and safety of faster aspart versus IAsp in subjects with T1D or T2D [28][29][30][31][32][33][34][35]. This review summarises the results from clinical pharmacology trials with faster aspart and relates these findings to the clinical benefits associated with faster aspart compared with IAsp based on outcomes from the phase III trials.…”