Faster aspart has a quicker onset of action, but does this impact glycemic control?
The goal of fast-acting insulin aspart is to mimic the physiologic action of endogenous insulin better. The addition of niacinamide and L-arginine to insulin aspart resulted in a quicker onset of approximately nine minutes, with a 150% greater glucose-lowering effect during the first 30 minutes after dosing than insulin aspart in patients with type 2 diabetes. Several studies have been completed that have examined the two insulins, including Onset 2, which included patients who were bolus-naïve and utilized insulin glargine for a 26-week study period. Faster aspart improved one-hour PPG and overall glycemic control compared to insulin aspart, successfully demonstrating noninferiority. Additionally, several studies have shown the importance of targeting postprandial glucose. In addition to improving overall glycemic control, there was a positive correlation between a higher level of PPG and intraocular pressure and an association with global cognition.
This study’s purpose is to confirm the effect in terms of glycemic control of treatment with faster aspart compared with insulin aspart (IAsp), combined with insulin degludec, with or without metformin in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen. An additional purpose was to test superiority in terms of PPG regulation while evaluating the safety profile of both regimens. A multicenter, double-blind, treat-to-target, randomized, parallel-group design was utilized in this study that randomized participants 1:1 with either faster aspart or IAsp delivered in a basal-bolus regimen with once-daily insulin degludec with or without metformin. A total of 1091 adults diagnosed with diabetes for over ten years and a history of basal-bolus treatment for at least one year were randomized – 546 to faster aspart and 545 to IAsp. There was a 12-week run-in period, which allowed for basal insulin titration after participants switched from their previous basal insulin. Bolus insulin was administered 0-2 minutes before each main meal and was titrated twice weekly to achieve a glycemic target of pre-prandial and bedtime blood glucose between 71-108 mg/dL. All other diabetes medications were discontinued, apart from metformin. The primary outcome was changed from baseline in HbA1c 16 weeks after randomization. Secondary outcomes included change from baseline in one-hour PPG increment (measured after a meal test), FPG, PPG, and safety. Noninferiority has been confirmed if the upper boundary of the two-sided 95% confidence interval was ≤0.4%. Change from baseline in HbA1c 16 weeks after randomization was analyzed using an ANOVA model, and HbA1c and PPG responder endpoints were analyzed using a logistic regression model.
Baseline characteristics were similar across the two groups, including age, sex, metformin use at baseline, weight, baseline HbA1c, FBG, and diabetes duration. At the end of the 16-week treatment period, the observed mean HbA1c with faster aspart was 7.00% and with IAsp was 6.96%, successfully demonstrating noninferiority (estimated treatment difference (ETD) -0.04% [95% CI -0.11 to 0.03]; -0.39 mmol/mol [-0.15 to 0.37]; P < 0.001 for noninferiority). This study could not confirm superiority with faster aspart in terms of change from baseline in HbA1c; the superiority was confirmed in change from baseline in one-hour PPG increment using a meal test, with a decrease in blood glucose by 7.72 mg/dL in faster aspart and an increase in blood glucose by 1.52 mg/dL in IAsp (ETD -7.23 mg/dL [-11.92 to -2.55]; P = 0.001 for superiority). There was no difference in change from baseline in FPG between the treatment arms. The overall rate of severe or BG-confirmed hypoglycemic episodes was statistically significantly lower for faster aspart (ETD 0.81 [95% CI 0.68 to 0.97]; P = 0.019). Daytime and nocturnal rates were also lower with faster aspart (0.83 [0.70;0.99], P = 0.038, and 0.66 [0.49; 0.88]; P = 0.004, respectively). There was no significant difference in the change in weight from baseline between treatment arms.
Faster aspart was confirmed to be non-inferior to IAsp, demonstrated by a significantly lower difference in PPG at one hour and a similar mean HbA1c after 16 weeks in patients with long-standing type 2 diabetes not well controlled on a basal-bolus regimen. In addition, there was a significantly lower rate of overall hypoglycemia and daytime and nocturnal hypoglycemia than with IAsp. This study demonstrates that the switch to and optimization of insulin degludec led to sustained improvements in HbA1c in both treatment arms, indicating a successful treatment option for patients with advanced type 2 diabetes to improve glycemic control. Future studies could determine whether these two insulins have a difference in complex clinical outcomes.
- Faster aspart was confirmed to be non-inferior to insulin aspart, with a similar mean reduction in HbA1c over 16 weeks.
- Faster aspart significantly reduced one-hour postprandial glucose compared with IAsp.
- The overall rate of hypoglycemia was lower with faster aspart.
Lane, Wendy S et al. “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).” Diabetes care, dc192232. March 24. 2020, doi:10.2337/dc19-2232
Jessica Rogers, PharmD candidate, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences