Fast-acting insulin aspart efficacy confirmed in CSII setting
medwireNews: Fast-acting insulin aspart (FA) is as effective as insulin aspart (IAsp) for glucose control when used for continuous subcutaneous insulin infusion (CSII) in adults with type 1 diabetes, results of the onset 5 study show.
During the study, glycated hemoglobin (HbA1c) levels in 236 patients randomly assigned to receive CSII treatment with FA fell from 7.49% (58 mmol/mol) at baseline to 7.44% at week 16. This compared with a fall to 7.35%, from the same baseline level, among the 236 patients randomly assigned to receive CSII with IAsp.
The estimated treatment difference (ETD) of 0.09% was significantly lower than the noninferiority margin of 0.4%, indicating that treatment with FA is noninferior to that with IAsp, David Klonoff (Mills-Peninsula Medical Center, San Mateo, California, USA) and co-researchers report in Diabetes, Obesity and Metabolism.
And although the fall in HbA1c with IAsp was significantly greater than that with FA, the likelihood of achieving a HbA1c level below 7.0% (53 mmol/mol) did not differ between the two treatments, with rates of 20.3% and 23.3% for FA and IAsp, respectively.
In addition, following a standardized meal challenge, there was a significant improvement in 1-hour postprandial glucose (PPG) increment in the FA versus IAsp groups, with the former experiencing a reduction of 0.89 mmol/L (16.0 mg/dL) relative to baseline and the latter experiencing an increase of 0.05 mmol/L (0.98 mg/dL). Significant differences were also observed at 30 minutes and 2 hours.
There were also significantly lower incremental increases with FA than with IAsp in mean interstitial glucose at 1 and 2 hours after breakfast, lunch, and an evening meal, as well as across all meals combined (ETD at 1 hour of −0.21 mmol/L; −3.77 mg/dL).
However, despite “the positive PPG findings,” Klonoff and co-authors say “it is surprising that [FA] did not improve HbA1c to a greater extent than IAsp,” noting that FA was statistically superior in the onset 1 study of people with type 1 diabetes using multiple daily injections.
They note that individuals in the FA group had “higher nocturnal and pre-meal levels” of interstitial glucose that “may have countered the expected overall glycaemic benefit of improved PPG control.”
According to the investigators, it is unclear why there was such a rise in interstitial glucose in the FA group, but they suggest it could be because basal rate and bolus pump settings need “optimization to adjust delivery according to the distinct pharmacological profile of faster aspart.”
There was no difference between the two groups in the overall rate of severe or blood glucose-confirmed hypoglycemia, at 45.07 versus 45.29 episodes per patient–year of exposure with FA and IAsp, respectively, but there were more hypoglycemic events with FA than with IAsp during the first hour after the start of a meal (1.25 vs 0.71 per patient–year).
“This finding may be partly due to an imbalance when randomizing participants who had previously experienced severe hypoglycaemia during the run-in period. All three of these participants were randomly assigned to the faster aspart group and experienced 10 of the 21 episodes of severe hypoglycaemia during the treatment period,” the authors note.
By Laura Cowen
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