Insulin u-500

Although insulin u-500 has been available since the 1950s, the use has sharply increased in only the past five years as a result of increasing rates of obesity and insulin resistance.

Insulin u-500 is a concentrated form of regular insulin, containing five times the units of insulin per mL as u-100.  Although it is a regular insulin, its pharmacokinetic profile may more resemble that of NPH;  a dose of u-500 may last up to 8 or even 24 hours. and there is a delay associated with the peak of action.¹  Although the total dose of u-500 may be more completely absorbed than large doses of u-100, there is a delay in absorption. ² 

There have been limited pharmacokinetic studies done.  Despite the availability of algorithms for the initiation of insulin u-500, much of the conversion may be trial and error. ¹  Pharmacokinetic reports have shown that a sharp rise in insulin concentration occurs 30 minutes after the dose is injected and peaks at 5 hours.  Insulin level will remain high even at 7 hours.  Insulin u-500 should be given 30 minutes before eating. ^2,3

Initiation of insulin u-500 is recommended for patients that are taking greater than 200 units of insulin daily and have not reached or have difficulty maintaining their goal A1c.  The total daily dose (TDD) of insulin should be added up.  If the patient’s A1c is less than 8%, 10-20% of the TDD should be subtracted. ^1,3

Insulin u-500 has both basal and prandial insulin properties.  On initiation, the TDD can be divided into three doses to be taken with breakfast, lunch and dinner although adequate glycemic control has also been achieved with the use of insulin u-500 in two divided doses.¹  If the TDD is 200-300 units, initiate a BID dosing regimen; 300-750, a TID regimen, and for doses 750-2000 consider dosing four times daily⁴.

Dividing the total daily dose²:  

BID dosing: Give 60% TDD qAM, 40% qPM

TID dosing:  Give 40-45% qAM, 30-40% at noon, and 20-30% qPM

no greater than 10% should be given at bedtime

Insulin u-500 acts more as prandial insulin in some patients, others more as basal; it is unclear if this is due to patient weight, insulin resistance, or the dose given^2,3.  The extent of peaking in insulin concentration has varied between studies.³

The patient should be followed every 2 weeks.  If over half of the blood sugar levels are 70-130, no dose change is needed.  If patient is experiencing hypoglycemic episodes, the dose can be decreased 25 units daily.  For fasting glucose levels of 130-200, the dose can be increased 25 units daily and for fasting glucose levels greater than 200, the daily dose may be increased 50 units. ¹

Insulin u-500 is associated with more weight gain than regular insulin.  For every 1% decrease in A1c, a 2kg increase in body weight can be expected³.  Despite the weight gain, patients will be a decreased risk of diabetic complications later on because of more tightly controlled blood sugar.  Weight loss should continue to be emphasized in patients taking insulin u-500.  Decreased weight will improve insulin sensitivity and may allow the patient to eventually step back down to using insulin u-100.  Weight gain with the switch to this insulin should be something assessed as part of the risks and benefits to starting insulin u-500. ^2,3

References:

1.  Ballani P et al.  Clinical experience with u-500 regular insulin in obese, markedly insulin-resistant type 2 diabetic patients.  Diabetes Care 2006; 29(11):2504-5.

2.  Daily AM et al.  Extreme insulin resistance: indications and approaches to the use of u-500 insulin in type 2 diabetes mellitus.  Curr Diabetes Rep 2011; 11:77-82.

3.  Segal AR et al.  Use of concentrated insulin human regular (u-500) for patients with diabetes.  American Journal of Health System Pharmacists 2010; 67:1526-35.

4.  Cochran E et al.  The use of u-500 in patients with extreme insulin resistance.  Diabetes Care 2005; 28(5): 1240-4.