Page 16 - Delaware Medical Journal - May 2017

insulin, the supersaturation changes
its properties. Other studies of the pharmacokinetics of U-500 have shown that this insulin has both basal and bolus properties.4 In general, U-500 insulin takes effect within 30 minutes or less, similar to a bolus insulin. It also has effects for up to 24 hours, demonstrating its basal insulin properties.
Since U-500 insulin has such a prolonged duration of action it has been argued that it may be best suited to twice or three times daily monotherapy, without the use of other basal insulin.4 To further investigate this,
a euglycemic clamp study of 24 healthy, obese subjects was performed. The subjects were given single doses of U-500 insulin
at 50 units (0.4-0.6 units/kg) and 100
units (0.8-1.3 units/kg), and the amount of glucose needed to maintain euglycemia (glucose infusion rate, GIR) was measured. This study showed onset of action in <
15 minutes and a mean duration of action of 21 hours. The range of action was 13 variability seen with the use of insulin, and perhaps especially with U-500 insulin. The rate of insulin absorption and activity are known to be affected by multiple
ADMINISTRATION AND CLINICAL EFFECTIVENESS
U-500 insulin has an FDA approved indication for use only in patients that require greater than 200 units of insulin daily, without additional insulin or antihyperglycemic products, administered with meals in twice or three times per day injections.6 Multiple studies, however, have examined the use of U-500 insulin in other off label uses. These include the use of U-500 along with U-100 insulin in a basal and bolus regimen,6 delivered by insulin pump (continuous subcutaneous insulin infusion, CSII),3 bedtime administration, and in combination with metformin,
thiazolidinediones, and GLP-1 receptor agonists.6 No studies have demonstrated the superiority of any particular dosing regimen, and it appears that, like any diabetes therapy, the ideal characteristics need to be individualized to the particular patient. There is no evidence to support strictly limiting the use of U-500 insulin to only the FDA approved indications, although carefully designed randomized controlled trials have shown evidence
of improved glycemic control with two or three times daily dosing of U-500 insulin as monotherapy.11 Most published case series involving U-500 insulin have involved multiple daily injections (MDI) for dosing, however.
Converting a patient to U-500 insulin
is usually associated with improvement
in glycemic control. The average improvement in glycemic control from multiple published trials, as measured by the change in hemoglobin A1C (HbA1C), has exceeded a 1 percent (11mmol/mol) decline in all studies.6 A meta-analysis published in 2012 showed a mean HbA1C reduction of 1.6 percent.2 The duration of the studies is variable, however. The length has ranged from three to 36 months, with durable glycemic control sustained for up to three years.1 Most studies show a rise
in weight and in the total daily insulin dose when patients are converted to U-500 insulin, suggesting that these patients are under-dosed while on U-100 insulin. The discomfort from multiple large injections of U-100 insulin could be involved in this.
Hypoglycemia has been reported with U-500 insulin. Hypoglycemia is usually measured by episodes that require the assistance of others for treatment, and this is termed severe hypoglycemia. Severe hypoglycemia rates from U-500 have been variable. The prevalence has ranged from zero10 up to 15 percent, although self-titration of the insulin doses may have accounted for this
relatively high rate.10 The rate of severe hypoglycemia in the Humulin R U-500 Initiation Trial of 1.9 percent events/ patients/30 days seems typical.10 Several studies have documented both the cost effectiveness of U-500 insulin5 and improved patient satisfaction.1
NURSING CONCERNS WITH HUMULIN R U-500 INSULIN
There are a number of issues involving U-500 insulin that pertain to nursing care. For an outpatient starting on concentrated insulin, the patient must clearly understand this is a concentrated insulin that is used to control hyperglycemia in adults who need more than 200 units of insulin in a day. than standard insulin (500 units in 1 ml compared to 100units/ml). As with any insulin, the patient will need to understand the dosing frequency and timing. Unlike fast acting insulin, however, self-titration of U-500 is discouraged. The patient should understand to take U-500 exactly as they have been instructed and they must know the dose they are prescribed. This insulin should be take approximately 20 - 30 minutes before eating their meal.
During the education session prior to placing a patient on concentrated insulin, the patient must return demonstrate drawing up a dose of insulin using the
new U-500 syringe (Becton-Dickinson).
If a patient is using the U-500 Kwik Pen, they are instructed NOT to withdraw insulin from the U-500 Kwik pen using a syringe because severe overdose and severe hypoglycemia may occur. Clear instructions should be discussed and written down in the event a dose is forgotten, what to do if they overdose using the syringe, how long before it peaks and how long it stays active in the tissue. They should understand the vial is larger than U-100 vial. They cannot mix U-500 insulin with other insulins in
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Del Med J | May 2017 | Vol. 89 | No. 5