Humulin Regular U-500 Insulin: Practical Application in the Outpatient Setting Karen McAvoy RN, MSN, CDE Joslin Diabetes Center Affiliate at The Hospital of Central Connecticut January 22, 2013

Objectives: Identify the challenges of using large does of U-100 insulin in insulin resistant patients Discuss candidates for U 500 insulin therapy or when to initiate or transition a patient to U500 insulin List the advantages and disadvantages of using U-500 insulin Discuss the recommended dosing of U-500 insulin in insulin resistant patients. State the importance of patient education in the safety and use of U500 insulin therapy.

Challenges of Large Dose U-100 Absorption is significantly reduced at high doses of insulin Pain at the injection site due to large volumes of insulin Increased number of injections per day Large doses are split up more Insulin pens only carry 300 units with a maximum of 60 to 80 units in a dose Multiple injections per dose (and multiple pens) if patient is taking more than 200 units/day Cost becomes an issue with such large doses of insulin Increased insulin amount Need for more supplies Syringes, pens, and needles

Candidates for U-500 Insulin Therapy Initial years of using U500 were for Type 1 patients with severe insulin resistance with receptor abnormalities Now….for ……. Type 2 diabetes with insulin resistance requiring large doses of insulin Poor glycemic control despite > 200 units of insulin per day Large doses of insulin that need to reduce the amount of injections and cost Pain at the injection site due to large volumes of insulin Place Title Here in Header and Footer 9/18/2018

Reference: Data on File. Eli Lilly and Company.

Why U-500? Less volume can improve the absorption of insulin and improve insulin metabolism because U 500 insulin is very concentrated…U-500 is an insulin formulation that is 5 times more concentrated than usual U-100 insulin. U-500 insulin has the same peak as the usual U-100 regular insulin, but its duration is more like that of NPH, thus works as both basal and bolus insulin, so patients take less insulin by volume, and typically only one type of insulin. Cost Place Title Here in Header and Footer 9/18/2018

Volume Differences Between U100 and U500 Insulin Place Title Here in Header and Footer 9/18/2018

Humulin R U500 Insulin Action: How Does it Work? onset: 30 minutes Peak: 1.75 – 4 hours (mean about 3 hours) Duration of Action: 6 – 10 hours but could last up to 24 hours The action is similar to both Regular and NPH Both Basal and Bolus There is potential for severe hypoglycemia—18 – 24 hours after the initial injection Place Title Here in Header and Footer 9/18/2018

Advantages of switching to U-500 Allows the patient to receive much larger doses of insulin with less volume (for example, 100 units U 100 is 20 units of U-500 insulin) Will improve absorption at the site Decreased pain at injection site Fewer daily injections Only one kind of insulin-both basal and bolus A Decrease in A1C Average drop is 1.6% at same TDD of U-100

Disadvantages of U-500 Insulin Does not come in a pen, no U-500 syringe, low vision or impaired dexterity may need device—magni-guide works and magnifies 1.7 times!! Can use U-100 or tuberculin syringe, the ½ cc insulin is easier to obtain and easier for insurance coverage Hypoglycemia – potential for severe 18 – 24 hours after the initial injection, especially if skipped meal or unexpected activity Hypoglycemia Hypoglycemia may increase upon initiation but reduce in frequency with increased duration of use Weight gain Average weight is 4.2 kg (9.33 lbs)

Dosing recommendations Insulin is administered two to four times a day depending on the TDD It is not recommended to use in combination with other insulins To determine the starting dose the TDD of U-100 insulin can be converted 1:1 Greater percentage of TDD is administered in the morning Adjustments to therapy are based on weekly trends of pre-meal and bedtime glucose 2 hr postprandial readings cannot be relied on due to action profile of the insulin

Dosing for a TDD of 200-299 units Twice daily injections recommended 60% of the TDD in the morning and 40% in the evening Three daily injections can be used 40% to 45% of TDD with breakfast 30% to 40% of TDD at lunch 20% to 30% of TDD at supper If readings are less than 50 points from goal the adjustment increment is 5 points If readings are more than 50 points above target the adjustment increment is 10 points

Dosing for a TDD of 300-599 units Three daily injections with meals are recommended 40% to 45% of TDD with breakfast 30% to 40% of TDD at lunch 20% to 30% of TDD at supper Four daily injections can be used 30% of the TDD is administered before each meal 10% of the TDD is a bedtime injection If the readings are less than100 points from goal the dose is adjusted by 25 units If the readings are more than 100 points from goal the dose is adjusted by 50 units

Dosing for a TDD greater than 600 units Four daily injections is recommended 30% of the TDD is administered before each meal 10% of the TDD is a bedtime injection If blood glucose readings are not at goal then adjustments are made in 50 unit increments

Accurate Prescriptions Complete: Humulin R U-500 (concentrated) 150 units at breakfast draw to 30 unit mark on ½ ml U100 insulin syringe 80 units at dinner draw to 16 unit mark on ½ ml U 100 insulin syringe Disp: 1 vial Other tips: Patient Education about prescription Place Title Here in Header and Footer 9/18/2018

Patient Education: Important Points 5 Times stronger Humulin R U-500 insulin is dispensed as a 20 ml vial. It may take a few days for you to obtain the Humulin R U-500 from your pharmacy. Never adjust the dose, unless directed Take 30 minutes before the meal Do not mix U-500 insulin with any other insulin. Blood sugar levels under 70/always carry something with you. Adjusting for special circumstances. Place Title Here in Header and Footer 9/18/2018

Handouts Also Include……. Card to identify use of Humulin R U-500 insulin. Present the card at the Emergency Department or the Hospital Place Title Here in Header and Footer 9/18/2018

Practical tips……………. You can use a magni guide with Humulin R U-500 insulin Unopened vials in refrigerator, once opened room temperature for 28 days Take 30 minutes before meals Important to continue working with people on lifestyle modification including physical acitivity Wallet Card Free sample voucher for Lily for 1 vial of Humulin R U-500 Insulin Your suggestions to add to this list?? Place Title Here in Header and Footer 9/18/2018

References Taylor S. U-500 Concentrated Regular Insulin: Practical Application in the Outpatient Setting. The Nurse Practitioner 2012; 37 (9): 47-52 Segal A, Brunner J, Burch FT, Jackson J. Use of Concentrated Insulin Human Regular (U-500) for Patients with Diabetes. Am J Health-Syst Pharm 2010; 67: 1526-1535 Valentine, V. Don’t Resist Using U-500 Insulin and Pramlintide for Severe Insulin Resistance. Clinical Diabetes 2012. Vol 30: 80- 84.

Reference: Data on File. Eli Lilly and Company.