In the case of significant insulin resistance (defined as needing more than 200 units per day), multiple injections of insulin are needed throughout the day to keep the blood sugar in check.  There is no written rule about the maximum volume of insulin that can be absorbed by the subcutaneous tissue at one time, but many prescribers will split an insulin dose into multiple injections when dose requirements are approaching 70 units in a single administration.

An insulin pen can deliver 80 units, and the largest size insulin syringe can hold 100 units.  So if your insulin dose is somewhere between 60 and 100 units, you might need more than one injection to deliver all of that insulin at one time.  In order to avoid becoming a human needle cushion, concentrated insulins like Humulin R U-500 were developed.

What is the difference in insulin concentrations?

Most of the insulins on the market today are U-100 strength, meaning there are 100 units of insulin per mL.  Examples are Regular insulin, NPH, 70/30 and other mixed insulin, glargine and detemir.  U-500 concentrated insulin has 5 times the potency of U-100 insulin, giving 500 units per mL.  By reducing the injected volume, better absorption, less injection discomfort and decreased number of injections can be experienced.

Until recently, U-500 was the only concentrated form of insulin.  Since 2015, two concentrated basal insulins U-300 {Glargine (Toujeo)} and U-200 {Degludec (Tresiba)} have become available in the US.  These have a strength of 300 units per mL and 200 units mL, also resulting in smaller volumes injected. Dosing conversion charts are used to safely move from a U-100 insulin to U-500 insulin.

Who needs U-500 insulin?

Good candidates for U500 insulin are those whose total daily insulin dose exceeds 200 units per day, or need more than 2 units/kg/day.  Average insulin requirements are 0.5 to 1 unit/kg/day.

How many times a day is U500 injected?

U-500 is typically injected 2-4 times per day. It starts working in about 30 minutes, peaks around 2-4 hours and lasts up to 10 hours.  Your individual dose will likely require some adjustments to find the right number of injections and exact dose to match your needs.  

How is it delivered?

U-500 can be given in a variety of syringes, which can be confusing and a source of errors! Traditional U-100 syringes require the dose to be divided by 5 to find the correct marking on the syringe.  Tuberculin (TB) syringes can also be used, but are marked in mL for volume rather than units.  

A dedicated U-500 syringe is on the horizon for late 2016.  The manufacturer states that the new insulin syringe is a 0.5mL syringe with clear, bold U-500 scale markings in 5 unit increments and allows for dosing up to 250 units. Finally, a U-500 Kwikpen is available, using standard pen needles.


U-500 syringe

Is U-500 the about same price as other insulins?

U-500 insulin is significantly more expensive per 10-mL bottle than U-100 insulin, but the cost per unit is usually the same or sometimes less than other types of insulin.  Because it is more potent, the vial or pen will last longer. Check with your insurance plan on the exact price to avoid sticker shock at the pharmacy.

Why do some people require such high insulin doses?

There are many conditions that contribute to insulin resistance.  Excess weight is the most common reason, but certainly not the only one.  Physical inactivity, use of drugs like steroids, pregnancy, severe infections, sleep problems like sleep apnea, and simply older age can also play a role.  One of the most effective ways to improve insulin resistance is through diet and increased activity.

Safely using U-500 insulin

All diabetics should know how to treat a blood sugar low and have a source of sugar readily available in case they need it.  Everyone on insulin, and especially U-500, should fully understand how to draw up and deliver the proper dose.  If you are even slightly unsure, contact your doctor or pharmacist to clear things up. In people with significant insulin resistance, the concentrated insulins can be an excellent tool in helping keep blood sugar controlled, without an enormous number of injections each day.

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