medwireNews: Fast-acting insulin aspart (faster aspart) results in equal, but not better, glycemic control to insulin aspart (IAsp) in adults whose long-standing type 2 diabetes is not adequately controlled with a basal–bolus regimen, a trial conducted in 17 countries suggests.
The phase 3b Onset 9 trial revealed an estimated treatment difference of 0.04% (0.39 mmol/mol) in the primary endpoint of change in baseline glycated hemoglobin (HbA1c) 16 weeks after its 1091 participants were randomly assigned to faster aspart or IAsp, with both treatments used in combination with insulin degludec with or without metformin.
The researchers acknowledge that the superiority of faster aspart over IAsp “could not be confirmed” in statistical analysis but add that the former did result in significantly better post-prandial glucose (PPG) regulation 1 hour after a meal at 16 weeks compared with baseline, with an estimated treatment difference of 0.40 mmol/L (7.23 mg/dL).
This finding was supported by a significantly greater increase in 1,5-anhydroglucitol with faster aspart than with IAsp, with an estimated treatment difference of 0.50 mg/mL at 16 weeks.
“Together, these findings are encouraging given that patients with advanced type 2 diabetes (~19 years in the reported study population) treated with a basal-bolus regimen represent a difficult patient population to manage, with PPG control being particularly challenging,” the researchers report in Diabetes Care.
Faster aspart also resulted in significantly fewer episodes of severe or blood-glucose-confirmed hypoglycemia than IAsp, including both daytime and nocturnal rates, with an estimated treatment ratio in favor of faster aspart of 0.81.
This is in line with recent trial post-hoc analyses in patients with type 1 diabetes indicating less nocturnal hypoglycemia with faster aspart versus IAsp, note the researchers led by Wendy Lane (Mountain Diabetes and Endocrine Center, Asheville, North Carolina, USA).
“These findings demonstrate that these next-generation insulins, faster aspart and insulin degludec, can provide important clinical value in tailoring of complex basal-bolus regimens to limit the incidence of hypoglycemia for patients with advanced type 2 diabetes,” they say.
Onset 9 included adults at 165 sites who had been diagnosed with type 2 diabetes for at least 10 years, had been treated with a basal–bolus insulin regimen for at least a year and had HbA1c of 7.0–10.0% (53–86 mmol/mol) at screening.
Participants undertook a 12-week run-in period when they were switched from their previous basal insulin to insulin degludec once daily, at 100 units/mL, to allow for basal insulin titration.
Following this, patients who still had an HbA1c of at least 9.0% (75 mmol/mol) were randomly assigned to receive either faster aspart (n=546) or IAsp (n=545), both at 100 units/mL administered within 2 minutes of each main meal, together with once-daily insulin degludec with or without metformin.
During the run-in period there were considerable HbA1c improvements, with mean levels dropping from 8.25% (66.69 mmol/mol) to 7.15% (54.64 mmol/mol) in participants subsequently assigned to faster aspart and from 8.28% (67.01 mmol/mol) to 7.05% (53.54 mmol/mol) in those assigned to IAsp.
Bolus insulin was titrated twice weekly to achieve preprandial and bedtime blood glucose levels of 4.0–6.0 mmol/L (71–108 mg/dL), with participants titrating bolus insulin using a predefined dosing algorithm.
The researchers report that at the end of the 16-week treatment period, observed mean HbA1c was 7.00% (52.96 mmol/mol) with faster aspart and 6.96% (52.59 mmol/mol) with IAsp.
By Anita Chakraverty
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