Insulin Pump Therapy

Introduction The first insulin pumps, or continuous subcutaneous insulin infusion systems (CSII), were introduced in 1976. These early pumps were the size of a backpack and were unreliable. Since then, insulin pump therapy has made significant strides. Today insulin pumps are battery-operated devices the size of a cell phone, and when used in the appropriate population they allow for a more physiologic insulin delivery and may provide better blood sugar control. Currently, approximately 20% to 30% of patients with type 1 diabetes and less than 1% of patients with type 2 diabetes use insulin pumps. 1,2 However, insulin pumps are becoming more commonly used in patients with type 2 diabetes. This document discusses the basics of insulin pump therapy. Detail-Document #261203 This Detail-Document accompanies the related article published in PHARMACIST S LETTER / PRESCRIBER S LETTER December 2010 ~ Volume 26 ~ Number 261203 Insulin Pump Therapy sugar by ten (0.6) to 60 mg/dl (3.3 mmol/l). The higher the number, the more sensitive a patient is to insulin. Dawn phenomenon increase in basal insulin requirements in the early morning hours, in response to an increase in cortisol, growth hormone, glucagon, and adrenaline. In children younger than 12 years of age, a reverse dawn phenomenon may be seen. In children, blood glucose levels are higher in the late evening and early morning (9 pm to 3 am) and then decline in the early morning to early evening (3 am to 6 pm). Dual wave/combination bolus a method where a fraction of the bolus insulin dose is administered immediately, at the start of the meal, and the remaining bolus dose is administered over a period of time, for example one to three hours. This is thought to more closely mimic the body s endogenous first- and second-phase insulin release that occurs in response to carbohydrate ingestion. Insulin to carbohydrate ratio calculations to assist in programming the amount of insulin bolus to cover carbohydrate ingestion. Square wave/extended bolus a dose of insulin which is delivered over a specified time period, for example 30 minutes. This is used for the ingestion of high-fat or high-protein meals or in patients with gastroparesis. Stacking a phenomenon which occurs when two insulin doses are given in close proximity. For example, a patient who administers a bolus Terminology In order to understand insulin pump therapy, there are a number of terms which must be understood. 3,4 Basal rate the amount of insulin needed to meet metabolic needs and maintain blood glucose levels between meals and at night. Bolus insulin delivery insulin doses calculated for meals, snacks, and to correct for elevated blood glucose levels. Bolus-on-board a feature of insulin pumps which estimates the amount of insulin remaining from the previous dose. This prevents stacking. Carbohydrate factor number of carbohydrates (in grams) that one unit of insulin for a meal, but has a snack two hours later will will cover or blunt. For example, in most patients, require additional insulin. However, insulin the carbohydrate factor is between five and 20. In remaining from the mealtime dose must be a patient who is sensitive to insulin, the considered when deciding the bolus dose needed carbohydrate factor may be 20, meaning that one for the snack. unit of insulin will cover 20 grams of ingested Total daily dose total of all the insulin carbohydrate. required in a 24-hour period. Correction factor the number of points (mg/dl or mmol/l) blood glucose drops for each Insulin Pumps unit of rapid-acting insulin. The correction factor Insulin pumps are designed to better mimic typically varies between ten (0.6) and 60 (3.3), physiologic endogenous insulin secretion. In a meaning that one unit of insulin reduces blood

(Detail-Document #261203: Page 2 of 7) person without diabetes, the pancreas secretes a basal amount of insulin throughout the day and similar information, insulin pump therapy appears justified for basal-bolus insulin therapy in patients night. This basal rate can vary. 5 For example, the with type 1 DM who are not adequately controlled rate of basal insulin is higher during the early morning hours (usually between 4 am and 9 am) in response to increases in cortisol, glucagon, adrenaline, and growth hormone. Following the ingestion of food, the pancreas rapidly releases a bolus of insulin initially, followed by a gradual release of insulin over the next one to three hours (also known as first- and second-phase insulin release). 4 Patients using an insulin pump are able to with multiple daily doses of insulin. 9 Information regarding the use of insulin pump therapy in patients with type 2 diabetes is limited. In a review of four randomized controlled trials in patients with type 2 DM, no difference in A1C or hypoglycemic events was noted in patients using multiple daily doses of insulin compared with insulin pump therapy. However, a nonsignificant trend in reduced insulin requirements was found in patients who used insulin pump therapy. 10 receive insulin more closely mimicking endogenous insulin release than those who use multiple daily injectable doses of insulin. Most Patient Population Appropriate patient selection is vital to the insulin pumps use rapid-acting insulin success of insulin pump therapy. 1 Insulin pump preparations (lispro [Humalog], aspart [NovoLog, NovoRapid in Canada], glulisine [Apidra]). Technically regular insulin can be used in a pump, but it is not ideal because it is absorbed too slowly therapy is not appropriate for all patients with diabetes. Rather, the ideal patient would be a patient with type 1 diabetes or a patient with type 2 diabetes and absolute insulin deficiency who to mimic physiological pancreatic function. Also, desires tighter glucose control. 1,2 Patients should in insulin pumps rapid-acting insulin may provide be administering at least four insulin injections better glycemic control without increasing daily and should be self-monitoring blood glucose hypoglycemia compared to regular insulin. 6 Lastly, most newer insulin pumps (MiniMed Paradigm Revel, etc) are tested using rapid-acting insulin analogs rather than regular insulin. Currently available pumps are able to provide multiple basal insulin rates at specific time frames, depending on time of day and other factors such as illness, exercise, and menstrual cycle. In addition, more recent pumps calculate an appropriate insulin bolus dose based on at least four times daily. Patients must be motivated, willing, intellectually and physically able, and be comfortable with the technology. In addition, patients should be willing and able to learn carbohydrate counting, and understand insulin adjustment and correction factors. They must have demonstrated excellent compliance in the past and be willing, at least initially, to maintain frequent contact with members of the healthcare team. 1 carbohydrate content, correction factor, and carbohydrate factor. Bolus insulin doses can be Indications for Insulin Pump Therapy delivered in a variety of manners including There are a variety of situations where more immediate bolus, dual wave/combination bolus, or physiologic delivery of insulin is necessary. 5 square wave/extended bolus. 1,7,8 These include: A number of clinical studies have compared Failure to achieve targeted A1C. One reason multiple daily doses of insulin with insulin pump patients may remain hyperglycemic is fear of therapy in patients with type 1 diabetes. A review hypoglycemia. By using insulin pump of 23 studies involving 976 patients found a therapy, patients can more closely tailor their significantly lower A1C in insulin pump patients insulin regimen to their nutritional intake and of approximately 0.3% [95% confidence exercise, thereby avoiding hypoglycemia. interval, 0.1 to 0.4%]. In addition, patients who Also, by using a basal, peakless dose, used insulin pumps had greater improvements in hypoglycemic reactions are reduced. quality-of-life measures. Severe hypoglycemia Exercise. Patients are often instructed to appeared to be reduced in users of insulin pump avoid exercise while insulin is peaking. This therapy, although no difference between regimens can be problematic in patients who administer was observed for the frequency of less severe multiple daily doses. With pump therapy, hypoglycemia. Based on this review and other

(Detail-Document #261203: Page 3 of 7) patients can suspend therapy and/or reduce the basal rate during exercise 16 to avoid hypoglycemia. Dawn phenomenon. In patients who experience dawn phenomenon, insulin pump therapy can be used to avoid this. By programming an increased basal rate of the pump during the early morning hours, hyperglycemia can be avoided. Pregnancy. Insulin pump therapy has been successfully used in pregnant patients with type 1 diabetes, 16 type 2 diabetes, and gestational diabetes. Insulin pump therapy allows tight glycemic control thereby preventing glycemic-related fetal malformations and obstetric complications. Gastroparesis. Gastroparesis can make blood glucose levels erratic and unpredictable. Pump therapy can be used to deliver bolus insulin doses over an extended period of time to better match the slowed absorption caused by gastroparesis. Changing work/meal schedules. Patients who work different shifts often have difficulty with glucose control. With insulin pump therapy, patients can adjust the basal rates depending on the shifts, allowing improved glucose control. Pediatric patients. Pediatric patients may require minute insulin doses such as 0.1 units of bolus insulin or basal rate alterations of 0.05 units. Using an insulin pump, these minute doses can be easily accommodated. Advantages and Disadvantages of Insulin Pump Therapy Insulin pump therapy is associated with a number of advantages and disadvantages. 1,4,5 With appropriate use, insulin pump therapy more closely mimics physiologic insulin release which may lead to tighter, more precise glucose control, less glycemic variability, and prevention of the dawn phenomenon. Tighter control of diabetes has been shown to reduce the risk of microvascular and macrovascular complications associated with diabetes. 11 In addition, pump therapy may be associated with a reduction in severe hypoglycemia and nocturnal hypoglycemia. 1,4,5 Newer pumps include built-in warning systems and alarms when glucose levels are low. Fewer episodes of hypoglycemia can lead to improved quality of life. 1,4,5 A major disadvantage of insulin pump therapy is the cost. Insulin pumps can exceed $6000 to $7000. In addition, supplies such as tubing and cartridges and for glucose monitoring are needed every month. Infusion site reactions (dermatitis, infection) and the risk of diabetic ketoacidosis must be considered. Because the patient is using only short- or rapid-acting insulin, even a temporary interruption of therapy can lead to diabetic ketoacidosis within a few hours. Patients who choose to use an insulin pump must be highly motivated and competent, and must accept the fact that they are tethered to the pump. This is a common psychosocial limitation, especially in adolescents who do not want others to know they have diabetes. 1,4,5 How to Choose a Pump Once a patient decides to use an insulin pump, the decision of which pump to use must be made. All marketed insulin pumps are reliable, but vary slightly in terms of features. 9,10 Questions to consider include: Is it waterproof? Most pumps are water resistant, but the duration and depth of water vary. How much does the insulin reservoir hold? Currently marketed pumps vary from 176 units to 315 units of rapid-acting insulin. What is the minimum basal increment? The basal increment varies from 0.025 units to 0.1 units. For a child requiring very small dosage adjustments, a pump with 0.025 unit increment may be desired. How many basal rates can be programmed? Currently available meters vary. For example, the insulin pump allows three patterns with up to 48 rates each and the OmniPod insulin pump allows for seven patterns with up to 24 rates. What is the bolus range? Insulin pumps typically start at a lower range of 0.05 to 0.1 units and can give as much as 10 to 35 units, depending on the pump. Boluses are administered over one to 40 seconds depending on the pump. Boluses can be

administered in a variety of methods including normal, extended, dual wave, or square wave depending on the meter. How much does the unit weigh? Pumps weigh between 3.8 ounces and 4.4 ounces including a full reservoir and batteries. What types of batteries are needed? Insulin pumps use AA, AAA, 1.5 volt lithium, or 3.6 volt lithium batteries. These batteries last between two to six weeks. What type of infusion set is used? Some insulin pumps are compatible with any brand of Luer-Lok tubing, while others only work with tubing made for that specific pump. The OmniPod insulin pump does not use tubing, but rather the pod has a built in infusion set, cannula, and inserter. The entire unit is discarded every 72 hours. Is there a food database programmed into the pump to assist with carbohydrate counting? Some pumps include a database of between 500 and 1,000 common foods which can assist a patient in determining carbohydrate values. However, not all pumps have this feature. Does it interact with a blood glucose meter? Some pumps will wirelessly transmit blood glucose information to a blood glucose meter, while the OmniPod insulin pump has a built-in glucose meter. Name of Insulin Pump Accu-Chek Spirit Amigo Dana Diabetescare IIS Deltec Cosmos (discontinued, but in use until warranty expiration) MiniMed Paradigm 522 MiniMed Paradigm 722 (Detail-Document #261203: Page 4 of 7) However, none of these meters are able to calculate an insulin dose and tell the pump how much insulin to administer. The patient must still input insulin dosing information into the pump at every meal or snack. Does it use continuous glucose monitoring? One pump (MiniMed Paradigm Revel) has continuous glucose monitoring equipment which can be purchased separately. This monitoring system can be set to alarm when blood glucose levels are too high or low. How complex is the meter? Most pumps will list the number of steps necessary to program a bolus or basal rate. Currently available meters typically require three to four steps for a single bolus. For a tworate basal pattern, pumps vary between nine and 13 steps. What is the memory? Memory varies considerably between the meters. For example, some meters maintain the last 90 events, while others retain 90 days (up to 5400 records) of data. The table below lists the available insulin pumps, including manufacturer contact information. 7,8 Manufacturer and Contact Information Disetronic Medical Systems (Roche) 800-280-7801 www.accu-chekinsulinpumps.com Nipro Diabetes Systems 888-651-7867 www.niprodiabetes.com Sooil 866-747-6645 www.sooilusa.com Smiths Medical 800-258-5361 www.smiths-medical.com

(Detail-Document #261203: Page 5 of 7) Name of Insulin Pump MiniMed Paradigm Revel MiniMed Paradigm VEO OmniPod One Touch Ping Solo MicroPump Getting Started on Insulin Pump Therapy Initiating insulin pump therapy requires extensive patient education and training, close follow-up, and dosage adjustments. Most adult patients can start insulin pump therapy as outpatients, but children are sometimes hospitalized during the initiation period. 1,4,5,12 Patients who are starting insulin pump therapy should stop all intermediate- and long-acting insulin 12 to 24 hours prior to pump initiation. Hyperglycemia can be treated with short- or rapid-acting insulin. Initial doses are calculated based on the total daily insulin doses prior to pump therapy. Because insulin pump users typically require less insulin, the calculated daily insulin dose should then be reduced by 10% to 20%. In general, 40% to 50% of the calculated insulin pump dose should be given as basal insulin and the remaining dose is delivered as pre-meal boluses. Basal rates throughout the day can be calculated by having a patient fast for a meal and determining the basal insulin rate that prevents a 30 mg/dl (1.7 mmol/l) or more increase or decrease in blood sugar. Patients should vary the meal that is skipped to determine different basal rates throughout the day and night. Pre-meal bolus doses can be determined by the preprandial glucose concentrations as well as the carbohydrate content of the meal, carbohydrate factor, insulin to carbohydrate factor, activity level after the meal, and prior experience. Following initiation, close monitoring is necessary to adjust insulin doses appropriately. 1,4,5 Manufacturer and Contact Information Insulet Corporation 800-591-3455 www.myomnipod.com Animas (Johnson and Johnson) 877-937-7867 www.animas.com Mendingo 800-SOLO-4YOU www.solo4you.com Patients should understand the importance of regularly monitoring blood sugar values (at least four to six times a day). In addition, insulin pump therapy requires extensive attention to details to continually input data into the pump regarding meals and snacks, exercise and activity, blood sugar values, etc. Patients should be instructed to change the catheter site every two to three days. Failure to rotate the insertion site can lead to scar tissue formation and subsequent variations in insulin absorption and blood sugars values. Insulin Pumps in the Hospital Patients receiving insulin pump therapy may be hospitalized for an acute situation. According to the American Diabetes Association, pump therapy can be continued during hospitalization, as long as the patient has adequate oral intake and is able to self-manage their care. Patients must record insulin doses which then becomes part of the medical record. It is important that the patient s medical chart clearly states that the patient is using an insulin pump, especially if the patient is having surgery. Also, patients must remove the pump prior to any electromagnetic procedures such as an MRI. In patients who are too ill to self-manage their insulin pumps, appropriate subcutaneous insulin doses should be determined and administered until insulin pump therapy can be resumed. 13 Reimbursement and Training Medicare and most insurance companies will cover at least part of the expenses associated with

insulin pump therapy as long as specific criteria are met. Patients must be insulin-dependent and have a fasting C-peptide level of 110% or less of the laboratory s lower limit of normal or demonstrate beta-cell autoantibodies. The concurrent fasting glucose level must be 225 mg/dl (12.5 mmol/l) or lower. 14 In addition, the patient must have documentation of at least one of the following: A1C greater than 7%, recurrent hypoglycemia, wide fluctuations of blood glucose before mealtimes, or the dawn phenomenon. 1 Pharmacists and other healthcare professionals can receive pump training from pump manufacturers such as and Animas. Some pharmacists who are certified pump trainers then receive reimbursement from the pump company for initially training and managing patients for up to two months. Typically pharmacists who attend these programs have credentialing such as Certified Diabetes Educator (CDE) certification or Board Certification in Advanced Diabetes Management (BC-ADM). In the U.S., additional patient training beyond the two month period provided by the pump company may be reimbursed under diabetes and selfmanagement codes (Healthcare Common Procedure Coding system codes G0108 and G0109) if the healthcare professional works in an American Diabetes Association-recognized program. 14,15 Users of this document are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and Internet links in this article were current as of the date of publication. Project Leader in preparation of this Detail- Document: Neeta Bahal O Mara, Pharm.D., BCPS References 1. Grunberger G, Bailey TS, Cohen AJ, et al. Statement by the American Association of Clinical Endocrinologists Consensus Panel on insulin pump management. September/October 2010. (Detail-Document #261203: Page 6 of 7) http://www.aace.com/pub/pdf/insulinpumpmanage ment.pdf. (Accessed November 11, 2010). 2. Wittlin SD. Treating the spectrum of type 2 diabetes: emphasis on insulin pump therapy. Diabetes Educ 2006;32:39S-46S. 3. Bradley BA. Insulin pump basics. Diabetes Health 2004. http://www.diabeteshealth.com/read/2004/07/01/40 28/insulin-pump-basics. (Accessed November 11, 2010). 4. Potti LG, Haines ST. Continuous subcutaneous insulin infusion therapy: a primer on insulin pumps. J Am Pharm Assoc 2009;49:e1-13. 5. White RD. Insulin pump therapy (continuous subcutaneous insulin infusion). Prim Care 2007;34:845-71. 6. Radermecker RP, Scheen AJ. Continuous subcutaneous insulin infusion with short-acting insulin analogues or human regular insulin: efficacy, safety, quality of life, and costeffectiveness. Diabetes Metab Res Rev 2004;20:178-88. 7. Anon. Insulin pumps and infusion sets. Diabetes Forecast. 2010 Consumer s Guide. http://forecast.diabetes.org/insulin-pumps. (Accessed November 11, 2010). 8. Anon. Insulin pumps. www.diabeteshealth.com/media/pdfs/prg2010/4- Insulin_Pumps_Chart-Diabetes_Health_2010.pdf. (Accessed November 11, 2010). 9. Misso ML, Egberts KJ, Page M, et al. Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus. Cochrane Database Syst Rev 2010; (1):CD005103. 10. Monami M, Lamanna C, Marchionni N, Mannucci E. Continuous subcutaneous insulin infusion versus multiple daily insulin injections in type 2 diabetes: A meta-analysis. Exp Clin Endocrinol Diabetes 2009;117:220-2. 11. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-86. 12. Scheiner G, Sobel RJ, Smith DE, et al. American Association of Diabetes Educators. Insulin pump therapy: guidelines for successful outcomes. September 2008. http://www.diabeteseducator.org/export/sites/aade/ _resources/pdf/insulin_pump_white_paper.pdf. (Accessed November 11, 2010). 13. American Diabetes Association. Standards of medical care in diabetes 2010. Diabetes Care 2010;33(Suppl 1):S11-61. 14. Centers for Medicare and Medicaid Services. Medicare National Coverage Determinations Manual. (Revision 124, September 24, 2010). https://www.cms.gov/manuals/downloads/ncd103c 1_Part4.pdf. (Accessed November 11, 2010). 15. Boyd LC, Boyd ST. Insulin pump therapy training and management: an opportunity for community pharmacists. J Manag Care Pharm 2008;14:790-4.

(Detail-Document #261203: Page 7 of 7) 16. Canadian Diabetes Association. Clinical practice guidelines for the prevention and management of diabetes in Canada (2008). Can J Diabetes 2008;32(Suppl 1):S1-S201. Cite this Detail-Document as follows: Insulin pump therapy. Pharmacist s Letter/Prescriber s Letter 2010;26(12):261203. Evidence and Advice You Can Trust 3120 West March Lane, P.O. Box 8190, Stockton, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249 Subscribers to Pharmacist s Letter and Prescriber s Letter can get Detail-Documents, like this one, on any topic covered in any issue by going to www.pharmacistsletter.com or www.prescribersletter.com