Page 15 - Delaware Medical Journal - May 2017
P. 15
SCIENTIFIC ARTICLE
Introduction
The dramatic rise in obesity in our society has played a direct role in the parallel rise in type 2 diabetes. There are a growing number of patients that require very high doses of insulin due to insulin resistance. There are both genetic and environmental causes of insulin resistance. The amount of insulin required to maintain acceptable glycemic control is usually proportional to the individual’s weight. Severe insulin resistance greater than 2 units/kg/day, or requirements in excess of 200 units/day.1,2 This usually requires patients to either administer insulin via multiple injections or to use a concentrated formulation of insulin. The most commonly used concentrated insulin is U-500 insulin (Humulin ® R U-500, Eli Lilly and Company, Indianapolis, Ind.).
U-500 insulin has unique pharmacologic properties that make it useful in the treatment of hyperglycemia in the setting of extreme insulin resistance. There
are also a number of safety concerns regarding this insulin, with risks and complexity inherent in the dosing.
In this review we examine the properties of U-500 and propose an approach to the use of U-500 insulin that may improve its safety.
METHODS
A literature search for English language articles that reference U-500 insulin was performed. The 51 articles, and additional websites as applicable, were independently reviewed.
HISTORY OF U-500 INSULIN
Iletin (beef) U-500 regular insulin was
FIGURE 1
Pharmacokinetic properties of U-500 regular insulin 9.
3 In the era prior to recombinant human insulin and insulin analogs, insulin was obtained from animal sources (i.e. porcine and bovine). On occasion this would be associated with requiring large doses of insulin. The current formulation, human regular U-500 insulin, has been available since 1997. The use of U-500 has increased dramatically in the
last decade. Between August 2008 and September 2010 there was a 97 percent increase in the use of U-500 insulin.4 This may be related to both the increased need by obese patients and an increase in patients and clinicians that are comfortable with
the use of concentrated insulin.5 Initially U-500 insulin was used in patients with severe insulin resistance syndromes, as well as conditions frequently associated with
the need for large doses of insulin, such as Cushing syndrome, acromegaly, and drug- induced insulin resistance. More recently, U-500 insulin has been used frequently for obese patients with type 2 diabetes.
As described below, U-500 insulin is now
available in a pen and a syringe dedicated to U-500 insulin.
PROPERTIES OF U-500 INSULIN
concentrated (500 units/ml) than regular human insulin (100 inits/ml). This allows higher doses of insulin to be administered in smaller injection volumes. The result of this is an improved patient experience, with reduced discomfort and fewer injections.6 In addition, there may be improved
insulin absorption when compared to a subcutaneous injection with higher volumes of insulin.6
U-500 insulin appears to have unique pharmacologic properties. The actions of Galloway et al. in healthy male volunteers.7 time to the peak response of U-500 insulin than seen with U-40 or U-100 regular insulin. Although U-500 is human regular
Del Med J | May 2017 | Vol. 89 | No. 5
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