Insulin found to provide better control of post-prandial glucose without significantly elevating hypoglycemia risk.
Type 1 diabetes is usually detected early in childhood or youth, which prompts them to use daily insulin therapy for life. This is also a period of continuous changes in diet, body weight and insulin sensitivity, and parental assistance. All these factors make their therapy more difficult to adjust. As a result, these young patients seldom meet their HbA1C goals. The use of rapid-acting insulin represents an advantageous therapy approach for reducing post-prandial glucose levels when they are not properly controlled with long-acting basal insulin. Commonly used fast-acting agents include: Lispro (Humalog) and Aspart (Novolog) insulin; however, they may not get absorbed fast enough to achieve the glycemic targets as well as delay the elimination, which may cause post-meal hypoglycemia. The introduction of faster-acting insulin may offer earlier exposure and higher absorption compared to normal fast-acting insulins. Faster-acting insulin Aspart (FIAsp) has already been approved in adults achieving great outcomes controlling the HbA1c when tested versus normal Aspart (IAsp). The focus of the following study is to test the effectiveness and safety of faster-acting insulin in children and youth.
A randomized, double-blind, single-center crossover trial in Germany tested faster aspart in children ages 6 to 11, adolescents ages 12 to 17 and adults (over 18 years old). Patients who had major comorbid diseases or had been using insulin treatment for less than a year were excluded. The study included 3 single visits separated from 3 to 22 days, in which they were administered either faster Aspart or IAsp 0.2 units/kg SQ dosing immediately prior to a standardized meal of 17.3 g carbohydrate/100 mL, which was adjusted by body weight. In a randomized sequence, both groups were treated with a blinded pen-injector prefilled pen. Then their blood was withdrawn for assessing pharmacokinetic values and glucose reductions in both treatment groups. Of the 55 screened individuals, 41 were randomized (13 children, 13 adolescents, and 15 adults) and 40 were exposed to trial product.
For all age groups, onset of insulin appearance occurred almost as twice as fast with faster Aspart vs IAsp. While t-max occurred significantly earlier for faster Aspart than for IAsp in adults (P = 0.03), the earlier t-max for faster Aspart vs IAsp in children and adolescents was not statistically significant. The onset of insulin exposure did not differ statistically significantly between age groups. The overall plasma glucose excursion appeared to be reduced for faster Aspart compared with IAsp, particularly in children and adults. In children, plasma glucose readings on average were reduced for faster Aspart vs IAsp by approximately 21-28 mg/dL at 1 and 2 hours intervals. Meanwhile in adolescents and adults, the difference in plasma glucose did not differ statistically significantly between treatment groups. At the end of the study only 8 participants per group had to be glucose alleviated of hypoglycemic symptoms. Both faster Aspart and IAsp were well-tolerated in all 3 age groups, and no safety issues were identified during the trial. There were no serious adverse events and most adverse events were mild.
The most relevant findings were a faster onset of action with greater early exposure observed for faster Aspart versus IAsp in children and adults. Faster Aspart showed significant reduction in the 2 hours post-prandial glucose excursion in children. Other studies on adults with T1DM suggest that faster Aspart may be given up to 20 minutes post meal with no impact on overall glycemic control or hypoglycemia risk as compared to IAsp dosed at mealtime, still this concept has not been tested in children yet.
A limitation of this study was the relatively low pool of participants in each age group, which may not reflect definitive pharmacokinetic or pharmacodynamic properties of an insulin product in a certain population.
In conclusion, the current findings of a faster onset and greater early exposure for faster Aspart vs IAsp in children and adolescents are in line with those in adults and suggest that the faster Aspart may induce better mealtime glucose control relative to current rapid-acting insulins, also in pediatric patients with T1DM.
- Faster Aspart insulin has proven to be a safe and effective controlling type 1 diabetes in children, teenagers and adults.
- Faster Aspart can provide better post-prandial glucose control without significantly elevating the risk of hypoglycemia.
- Faster Aspart insulin has quick onset of action with high early glucose exposure.
Maryam Fath, Thomas Danne. Faster-acting insulin aspart provides faster onset and greater early exposure vs insulin aspart in children and adolescents with type 1 diabetes mellitus. Pediatric Diabetes. February 2017.
Fabio Rodriguez, PharmD. candidate 2018, LECOM School of Pharmacy