Insulin: A 2014 Primer, Part 2 Insulin Delivery and Insulin Pumps
September 1, 2014
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Insulin: A 2014 Primer, Part 2 Insulin Delivery and Insulin Pumps
Editor’s Note
In Part 1, the authors reviewed the clinical aspects of insulin dosing and titration for primary care physicians. In this section, the authors review new and emerging insulin products, the practical aspects of writing insulin prescriptions, delivery of insulin, and advanced insulin delivery systems (via pump and patch).
Executive Summary
Primary care physicians need to be conversant with the accurate prescribing of insulin products and follow standardized nomenclature in order to effectively communicate with pharmacists to avoid prescribing errors.
- Most patients who plan to start insulin therapy prefer insulin pens as they are more portable and reduce the necessary equipment to carry. They hold 3 mL (300 units) compared to vials, which hold 10 mL (1000 units). Prescriptions need to include pen needle lengths as well.
- Each unit of lispro, aspart, and glulisine has similar glucose-lowering effects, allowing for accurate prescribing, dosing, and even switching between insulins.
- For patients taking more than 300 units of insulin per day, concentrated insulins such as HumuLIN R U500 can be given 30 minutes prior to meals but can have effects up to 24 hours due to pharmacokinetic issues.
- Emerging insulin products include inhaled and oral insulin delivery systems as well as "smart insulins," which have built-in glucose sensors that potentially can mitigate the serious issue of hypoglycemia.
- Insulin pumps were first introduced 30 years ago; in the United States, approximately 400,000 people use pump therapy. CMS has strict criteria for patient eligibility, as pumps can cost $2000-$8000 with $300/month maintenance.
Insulin Delivery
At present, all insulin products are delivered via subcutaneous insulin injections (see Table 1). Outpatient regimens most often are based on injections from a syringe and insulin drawn from a vial or delivery via an insulin pen. Insulin pens are available as reusable devices (pens) with replaceable insulin cartridges or disposable single-use pens.
Table 1: Available Insulin Products and Delivery Methods
Insulin Product |
Regular Insulin |
NPH |
Glulisine |
Aspart |
Lispro |
Detemir |
Glargine |
Afrezza |
Vial |
X |
X |
X |
X |
X |
X |
X |
|
Permanent refillable insulin pen |
X Echo pen Novo Jr. pen Novopen 3 |
X Luxura HD |
||||||
Disposable insulin pen |
X |
X Solostar pen |
X Flexpen |
X Kwikpen |
X Flexpen, Flextouch |
X Solostar pen |
||
Inhaler |
X |
Patients who currently use or plan to start insulin usually prefer insulin pens1 because they are more portable and allow for attachment of pen needles, thus reducing the necessary equipment the patient has to carry. Insulin pens hold 3 mL (or 300 units) of insulin, so they need to be replaced more often than vials, which hold 10 mL (1000 units). Additionally, adherence is improved for insulin pens compared to vials and syringe.2
Writing Insulin Prescriptions
Most insulin products in the United States are U100 insulin (100 units/mL), which translates as 100 units in each mL of insulin. This standardization is important in terms of safety and reliable clinical effect. Each "unit" is standardized for a similar clinical response — one unit of lispro, aspart, and glulisine should each have similar glucose-lowering effects — which allows for accurate prescribing and dosing, even when switching between insulins. A vial of U100 insulin holds 10 mL or 1000 units. An insulin pen holds 3 mL or 300 units.
Prescriptions for insulin pens also need to include pen needles, which come in regular (8 mm), short (5 mm), mini (4 mm), and nano (3 mm). Recent evidence has shown that all needle lengths are equally effective.3
Errors in insulin prescription and/or dosing are among the most common in inpatient and outpatient settings.4 To minimize the chance for error a few general rules should always be followed:
1. Always write out the word "unit" — do not use the abbreviation U as it can be mistaken for a 0.
2. The current recommended nomenclature (http://www.ismp.org/tools/tallmanletters.pdf) is to capitalize the last three letters of a brand name to limit confusion between similarly named products. For example: HumaLOG vs HumuLIN or NovoLOG vs NovoLIN.
3. Specify whether the prescription is for pens or vials.
4. Try to be as specific as possible so the pharmacist can help provide the correct instructions. Write NovoLIN R 6 units before each meal three times per day instead of writing Novolin R take as directed at mealtimes.
5. If a patient needs to take a correction dose, it should be spelled out on the prescription: Write HumaLOG 6 units per meal plus correction 1 unit for every 50 mg/dL above 150 mg/dL.
6. Always include the maximum dose per day on the prescription so the pharmacist can dispense the correct total volume.
The following is an example of what a prescription might look like: Apidra SolostarR pens, Take ApidraR 6 units per meal plus 1 unit for every 50 mg/dL above 150 mg/dL for a maximum of 40 units per day, 30-day supply, 5 refills.
Determining the Prescription Dose
Estimating the volume on the prescription is based on daily dose. Each vial of U100 insulin holds 1000 units. Dividing by a typical 30-day month corresponds to 33 units per day. To allow for different numbers of days per month, estimate 1 vial per month. If a person typically takes 40 units per day of insulin by vial, write for two vials. When prescribing vials, insulin syringes will also be needed. The current sizes for insulin syringes include 0.3 mL, 0.5 mL, and 1 mL, which allow for injections of 30 units, 50 units, and 100 units, respectively. Insulin pens hold 300 units of insulin and typically come in a box of five, for a total of 1500 units. This means that a person who uses 45 units per day of insulin will use one box of five pens per month.
Many electronic medical records can assist in the calculation of the volume needed. This can be made easier if the prescription is written in volume rather than units of insulin, particularly for concentrated insulin.
Concentrated Insulins
Patients who are obese and have type 2 diabetes typically need more insulin for a therapeutic effect, which often means very large doses of daily insulin (200-300 units per day). Once a person needs more than 300 units of insulin per day, the number of injections increases and the pharmacokinetics of the insulin can be less consistent due to potential depot effects at the injection site. Concentrated insulins are a potential solution to this challenge.
Regular human insulin is available in a concentrated form, HumuLIN R U500, with the same mechanism of action as U100 regular insulin. However, increased concentrations create more aggregation of insulin molecules into dimers/hexamers, thus prolonging absorption. HumuLIN R U500 contains 500 units/mL of insulin vs the non-concentrated form, which contains 100 units/mL. Each vial holds 20 mL of U500 insulin or 10,000 units, which is 10 times more than other vials. A single dose of concentrated U500 regular insulin may have effects up to 24 hours. HumuLIN R U500 is recommended for subcutaneous administration 30 minutes prior to a meal and is typically administered 2-3 times per day based on the dose.5
Concentrated U500 insulin can be an excellent tool when used appropriately. However, understanding dosing of HumuLIN R U500 is important to prevent severe hypoglycemia or death. Eli Lilly, which manufactures HumuLIN R U500, provides online information for assistance in prescribing concentrated insulin. The current recommendation is that dosing for this insulin be determined by volume and not by number of units in an effort to reduce dosing errors and improve safety. Humulin U500 insulin is currently only approved for subcutaneous insulin injections, but it has been used off-label in insulin pumps as well.
Case example: A 57-year-old male has had diabetes for 22 years. He tried a number of oral medications but has used insulin solely for the last 6 years. Over time, he has needed more insulin to get the desired glucose-lowering effect. He is currently taking insulin detemir 100 units twice daily, and insulin lispro 60 units at each meal (three times per day) and additional correction scale if he is higher than the target. The total insulin he is taking daily is at least 380 units. He reports that his glucose readings are typically high and he needs to add correction most of the time. He is not able to use insulin pens as the volume of each injection is more than the max dose for a single injection (larger volume than a single pen injection can give). He could give two injections each time with the pen but this becomes burdensome. His A1c is 9.8%. This person would be an ideal candidate for U500 insulin. His 5-10 injections could be reduced to three injections of U500 regular insulin.
When switching a person from traditional U100 insulin to U500, the best first step is to identify the total daily dose by adding the total number of units of all insulins given in 1 day. In this case example, the total daily dose is typically around 380 units. Next, divide the total daily dose by 5 (in this case example, 380 divided by 5 is 76 units). Then divide the total U500 insulin into the appropriate doses for each day. In our practice, we use two U500 injections if patients are on < 300 units of U100 insulin and three shots if patients are taking > 300 units of U100 insulin. To maximize safety, we prescribe HumuLIN R U500 regular insulin in volumetric quantities. We recommend a TB syringe or 1 mL insulin syringe. For the patient in this case example, we would recommend 0.76 mL of HumuLIN R U500. The dosage would be divided into thirds because he eats three meals per day. He will take 0.25 mL at breakfast and lunch and 0.26 mL with dinner. Based on the prolonged duration of action of this insulin, we can recommend dosing at breakfast, lunch, and bedtime or at breakfast, dinner, and bedtime based on the size and carbohydrate content of his meals. This reduces the number of injections, involves only one kind of insulin, and provides better stability of his glucose. Since HumuLIN R U500 insulin is more expensive than U100 insulin, it is important to consider the patients’ insurance coverage. In addition, some people are prone to swelling and weight gain on U500 insulin compared to U100 insulin.
Emerging Insulin Products
Researchers are constantly searching for innovative insulins and insulin delivery methods. Products currently in development include inhaled and oral insulin as well as insulin with different pharmacokinetics that allow them to be even more physiologic. In January 2006, an inhaled insulin product (Exubera®, Pzifer) came to market, but sales were not robust enough to continue its production.6
In June 2014, the FDA approved Afrezza® (MannKind Corporation),7,8 an rDNA human dry powder insulin indicated for both type 1 and type 2 diabetes. This inhaled insulin is combined with an inert excipient and used with the Technosphere® Inhalation System. An "ultra-rapid mealtime insulin," Afrezza is designed to reach peak insulin levels 12-15 minutes after inhalation and it is cleared faster than rapid-acting insulin. Therefore, it is dosed with meals. Afrezza is expected to be available in the United States in 2015. Most common side effects are cough, throat pain, headaches, and higher rates of hypoglycemia.7 This medication should not be used in people who smoke or have problems with moderate-to-severe asthma or COPD symptoms. In these patients, there is a black box warning for bronchospasm.
Dance 501 (Dance Biopharm Inc.) is an inhaled insulin device in development that releases an insulin mist with an appropriate inhalation from the patient.9 Dance 501 is being studied in adult patients with type 2 diabetes.
In addition, several novel concentrated insulins, including U200 and U300 basal insulins, are in development for patients who take large volumes of insulin. These concentrated insulins will most likely have longer durations of action. Glargine insulin, in a concentration 300 units/mL, appears to have a similar clinical effect with the U100 version.10
Degludec (NovoNordisk), a basal insulin with a duration of 42 hours, has been studied in a U100 and a U200 concentration.11,12 Although it is available in Europe, the FDA is requiring the manufacturer to produce additional cardiovascular outcome data.11 PEGylated insulin lispro (Lilly)11,13 is insulin lispro attached to a polyethylene glycol, which makes this molecule have a large hydrodynamic size and prolonged duration of action. This insulin may also have preferential hepatic uptake and may more closely approximate normal endogenous insulin physiology.
In addition, emerging "ultra-fast insulins" that may provide faster insulin coverage for meals and correction are in development to help prevent formation of dimers and hexamers. One promising approach is the use of hyaluronidase to speed absorptions and time to onset. Another option is to add excipients to speed insulin absorption or insulin dispersion.14
A new area of insulin technology is biosimilar insulin.15 Since many insulin analogs will go off patent in the coming years, manufacturers have the opportunity to make close copies, called biosimilars. Although the compounds may have the same amino acid sequence, they may have slightly different clinical characteristics when produced under different conditions. Biosimilars are available in other countries, but there are not enough data from controlled clinical trials to adequately compare them. The FDA has provided guidance for the development of biosimilars in the United States.16
The final products in development are "smart insulins," which have built-in glucose sensors that allow the insulin delivery component according to the ambient glucose. These have the potential to resolve the serious issue of hypoglycemia, which is a concern with current insulin formulations. Examples of smart insulins include protein-binding ligands (lectins) that can reversibly bind to carbohydrates and nanotechnology and nanoplugs that sense glucose levels and control insulin release from microgels or bioactive membranes. In addition, bulk hydrogel matrices, microgel sponges, and phenyl boronic acid in hydrogel have been reported to work like closed-loop insulin delivery devices. These hydrogels will swell in the face of hyperglycemia and in turn release insulin from its pores until the glucose normalizes. Although these technologies are exciting, they have only been researched in animal models at this time.17
Advanced Insulin Delivery
V-Go is a disposable patch insulin delivery device specifically designed for use in adults with type 2 diabetes.18 The V-Go includes many of the advantages of an insulin pump and it comes in a non-motorized plastic device that is disposable. V-Go is not an insulin pump as others will be described below, and is best used only in type 2 diabetes.
Unlike pumps, V-Go has a mechanical power source that delivers insulin with button presses rather than an electronic motor. Each disposable patch is used for 24 hours. The V-Go is waterproof to a depth of about 3 feet for 24 hours, so there is no need to remove the patch while swimming or bathing. It does not work with data management software.
Similar to insulin pumps, V-Go uses a rapid-acting insulin. Only U100 lispro and aspart insulin are approved to use with this device. V-Go pumps are available in three different sizes based on the basal doses patients will receive in a 24-hour interval. For example, the V-Go-20 pump delivers 20 units of insulin over 24 hours (20/24 units = 0.83 units per hour). The delivery devices are also available in 30- and 40-unit systems. Each pump is capable of delivering an additional 36 units of prandial insulin throughout the day through the discrete depression of a bolus button on the side of the pump.
The V-Go has a number of advantages. First, the V-Go is portable so patients do not have to carry insulin pens or a vial and syringes. In addition, some people require less insulin with this system for the same clinical effect compared with MDI because the delivery method is more effective. There may be increased adherence because of easy use and no need to take long-acting insulin, which may represent an expense benefit. Also, the V-Go system requires no exposed needles, which makes V-Go a simple, convenient, and preferred method of insulin delivery. Finally, the NDC code for each pump size indicates that the device should be dispensed as a drug rather than as a device. As such, the V-Go is covered by most insurance companies, including Medicare and Medicaid.
Disadvantages of the V-Go include the potential for insurance coverage issues, the potential for skin irritation from the adhesive pad, and a risk for infections at the infusion site. It is also less specific than an insulin pump, provding only one non-adjustable basal rate and fixed dosed boluses in 2-unit increments. Finally, this device should be removed before any magnetic resonance imaging (MRI) testing.18
Insulin Pumps
Insulin pumps were first introduced more than 30 years ago in the United States. Approximately 400,000 people use insulin pump therapy in the United States today.19 The January issue of Diabetes Forecast, published by the American Diabetes Association, includes a directory of all diabetes-related supplies, currently approved insulins, pumps, and injecting supplies, and is an excellent resource for patients and providers.20 Insulin pumps are a good option for people who are on multiple daily insulin injections.
In the most basic terms, insulin pumps are advanced and expensive syringes. Insulin is delivered from a reservoir in the insulin pump and provides a basal amount of a single insulin dose through a transcutaneous catheter. Further boluses of insulin can be manually provided in response to carbohydrate ingestion. Insulin pumps are battery-powered devices with software that allow patients to program in advance, temporarily adjust, or suspend insulin basal infusion rates. In addition, insulin pumps can deliver precise boluses. These continuous subcutaneous insulin infusion (CSII) delivery systems attempt to mimic the pancreas function. Insulin pumps deliver different basal insulin rates throughout the day based on changes in insulin sensitivity, which allows for greater precision for bolus insulin dose delivery relative to carbohydrate intake and absorption from the gastrointestinal tract. Rapid- or short-acting insulin should be used in the pump. Although not FDA-approved, Humulin R U500 insulin has been used successfully off label in insulin pumps to improve A1c without an increase in hypoglycemia.21,22
Insulin pumps are attached to patients by one of two means: 1) an infusion set consisting of long, thin, flexible tubing with a catheter or a stainless steel needle on the end that is inserted into the patient’s subcutaneous tissue, or 2) a tubing-free pump, also known as a patch pump, that is attached with a subcutaneous needle-inserted catheter and self-adhesive tape. The patient programs and operates the pump or the pump’s remote control device to deliver insulin doses that match individual needs. Patients must know that insulin pumps do NOT calculate the appropriate dose of insulin that will be given prior to eating. Patients and health care professionals should work together to calculate a patient’s daily insulin amounts, and patients program the pump to deliver insulin based on their specific requirements.23,24
The American Association of Clinical Endocrinologists (AACE) recommends considering a CSII device for type 1 and type 2 diabetes patients who have clear indications, including suboptimal control on a regimen of basal/bolus injections; not achieving glycemic goals despite maximal adherence to multiple dose insulin injections; wide and erratic glycemic excursions; frequent severe hypoglycemia; hypoglycemia unawareness; marked dawn phenomenon; pregnancy or planning for pregnancy; those people with erratic or unpredictable daily schedules/lifestyle; and patient preference.25
Who Is a Good Candidate for an Insulin Pump?
Type 1 or type 2 diabetes patients who are well versed in multiple daily injection therapy are good candidates for insulin pumps. These patients already check their glucose four or more times daily, inject insulin four or more times daily, perform carbohydrate counting, demonstrate the ability to adjust dosing appropriately, and are willing and motivated to work closely with the health care team to achieve optimal glucose control.25 Patients who can actively manage their diabetes will find that insulin pump therapy provides more real-time flexibility and some important safety features. However, patients who are looking for ways to take short cuts in their diabetes care are NOT good candidates for insulin pump therapy.
Programmable Settings on an Insulin Pump
Basal Rate. Basal rates are programmed by the provider. The basal insulin release is intended to replicate physiologic insulin release. For patients on subcutaneous injections, this replaces their glargine or detemir dose. Unlike current long-acting basal analogs that provide a steady state of insulin release, insulin pumps can be set to a few basal rates within any 24-hour period. This provides more physiologic matching of insulin delivery to hourly insulin needs based on a person’s daily schedule. With normal physiology, a person secretes very little insulin overnight while sleeping but needs much more in the early morning to midmorning hours based on growth hormone and cortisol secretion. Insulin needs the rest of the day are specific to the patients’ lifestyle. Insulin pump therapy can make the basal insulin match the patients’ lifestyle more closely than subcutaneous basal insulin injections.
Typically, patients who switch from injections to a pump need less insulin. It is customary to set the first pump dose at 75-80% of the previous injection dose to reduce the chance of hypoglycemia.
Carbohydrate (Carb Ratio). Many patients with type 1 diabetes and some with type 2 diabetes utilize carbohydrate counting to make the mealtime insulin match what they are about to eat. If done carefully, this can significantly reduce the risk of post-meal hyperglycemia and hypoglycemia. A provider or diabetes educator should work closely with each patient to determine a specific carb ratio. Then, with this knowledge, patients can estimate what they are about to eat and count the carbohydrate grams (or exchanges) at the meal. This number can be input into the pump and the insulin pump will calculate what dose of insulin is needed for that amount of carbohydrates. For example, a 1:20 carb ratio means that for every 20 grams of carbs to be eaten, the patient should take 1 unit of insulin. If a patient is going to eat 70 grams of carbs at a meal and the carb ratio is 1:20, the patient should input 70 carbs in the pump. Then the pump will indicate that the patient needs 3.5 units. Although this calculation is relatively straightforward, the pump can calculate a dose for any carb content and calculates to a fraction of a unit.
Correction Factor. Most people who are on subcutaneous injections have a "sliding scale" or correction scale. The term and typical use of "sliding scale" should be discouraged. Instead, it is recommended that a scale be used for correction of hyperglycemia to a target level, but it should be adjusted daily to specifically remove the need for that scale. The active adjust and individualization is the key difference. A correction scale describes how much the glucose is expected to drop per 1 unit of insulin given. This is set to correct to a desired target range. For example, if target glucose is 100 and the correction factor is 50, then the patient will take correction insulin when he/she is above 100, 1 unit for every 50 mg/dL above 100. A pump can dispense a fraction of a unit, e.g., 0.5 units if the glucose is 125 mg/dL.
Case Example: A person takes 24 units of glargine, uses aspart at meals with a 1:10 carb ratio, and takes a correction factor of 30. His target is 120 mg/dL. To program his pump, the first step is to program his basal rate. To start, take the total basal insulin and subtract 20% (24 units; 20% of 24 or 4.8 units). The remaining 19 units may be given either as one fixed basal rate of 0.79 units/hour (20 units/24 hours in a day) or as multiple basal rates so that less insulin is given during the nighttime and more in the morning when insulin resistance is the highest. The latter is more like physiologic insulin release. Next, enter the carb ratio, correction factor (also called sensitivity), and target blood glucose. The carb ratio and correction factor for insulin injections can remain the same for the pump. With the pump, different target glucose levels can be set for different times of the day. Commonly, a lower glucose level (or range) is used as the target during the day and a higher one toward bedtime and overnight to limit the risk of hypoglycemia.
In the case described above, we maintain the carb ratio of 1:10 and correction factor of 30 mg/dL. We set the target glucose 80-120 between 6 a.m. and 9 p.m. and 120-160 mg/dL between 9 p.m. overnight until 6 a.m.
Reverse Correction. This important safety feature can help keep a person at the target range. At a meal, a person can enter information for the carbohydrate content and current glucose into the pump. If the glucose is below the target range, the pump will automatically subtract insulin from the dose about to be given, allowing the person to bolus for a meal if below target and allowing him not to drop immediately back into the hypoglycemic range. While this is possible without an insulin pump, most people with diabetes "guess" how much less insulin they need or estimate a lower number of carbohydrates than they are really eating. Using the reverse correction is much more accurate.
Suspend Feature. When patients taking insulin injections start to experience hypoglycemia, the only thing they can do is eat something to treat the low. The insulin injection has already been taken and cannot be reversed. For someone who has lots of lows or has lows at night, this "forced eating" to treat a low rather than for hunger or nutrition can be problematic. This can make eating less pleasurable and can contribute to unintended weight gain. However, patients with an insulin pump who have a hypoglycemic episode first can suspend the pump so that no additional insulin is administered until it is safe again, and second eat to treat the low. This allows the person to eat less to treat a hypoglycemic episode and may prevent over-treating the low and thus prevent rebound hyperglycemia.
Active Insulin. This feature prevents a person from taking too much insulin or "stacking insulin boluses." Often after patients take a correction dose of insulin, their glucose is still high. If the second correction is given before the first correction has taken full effect, patients are at higher risk for dropping low by "stacking their insulin." Patients taking injections cannot know how much of the insulin from their meal is still working, so they make an educated guess about much additional insulin to take. With an insulin pump, the amount of time that insulin is acting can be programmed, which limits the amount of additional insulin that can be given with subsequent boluses within that window of time. In other words, this feature prevents patients from taking repeated injections while the previous injection is still acting, thus avoiding "stacking insulin." This is a great way to prevent hypoglycemia.
Case Example: A patient’s pump is set for an active time of 4 hours. His glucose after dinner was 300 mg/dL at 8 p.m. Since the target glucose is 100 mg/dL with a correction factor of 1 unit for every 50 above 100 mg/dL, the pump will deliver 300-100/50 or 4 units of correction insulin. If the patient’s blood glucose is still above target at 10 p.m. and the glucose 250 mg/dL, the normal correction dose would be 3 units. However, the pump would subtract the amount of insulin that is still predicted to take effect. As an example, the recommended dose would be approximately 1.2 units instead. With all boluses, the person can accept this suggestion or override it.
Temporary Basal Rate. This allows patients to increase or decrease the current basal for a set amount of time to respond to a change in their activity, physical state, or glucose. Often, the programmed basal rates will work for normal days but there will be exceptions that necessitate more or less insulin. For example, when a person gets sick with a respiratory illness or when a woman is menstruating, the glucose levels will rise significantly. Under these circumstances, patients can change their basal rate to a set level or by a percentage.
Case Example: A person is going to take a final exam. The stress of getting to and taking the exam has raised the patient’s glucose. In response, he may run a temporary basal of 150% for 4 hours when he is going to take the exam. This means that if the normal basal is 1 unit per hour, then during this 4-hour period it will be 1.5 units. It will automatically revert back to 1 unit per hour after 4 hours.
Advantages and Disadvantages of Insulin Pump Therapy
Intensive glucose control has clearly been shown to reduce microvascular complications in type 1 and type 2 diabetes as well to reduce macrovascular complications later in the disease.26-28 Intensive insulin therapy can include multiple daily insulin injections (MDI) or insulin pump therapy (CSII). Multiple studies have shown that insulin pump therapy with rapid-acting analog insulin improves glucose control and reduces hypoglycemia compared to MDI in type 1 diabetes.29-35 Insulin pump therapy is also equally effective in type 2 diabetes. The majority of patients (93%) with type 2 diabetes prefer insulin pump therapy over MDI.36,37
A 2010 Cochrane review compared insulin pump therapy to MDI and found that insulin pump therapy has better A1c reduction, improves quality of life, and appeared to reduce overall hypoglycemia rates.38
The advantages of CSII include improved adherence, increased dosing accuracy, lifestyle flexibility, improved control of the dawn phenomena without induction of nocturnal hypoglycemia, and suspension or temporary reduction in basal insulin to compensate for increased physical activity.
The disadvantages of CSII include a high degree of technicality, a high level of ongoing engagement, potential skin reactions to tape, diabetic ketoacidosis risk if the pump malfunctions, infusion-site problems (tunneling of insulin or clogged infusion set), and inactivated insulin (due to heat) that can lead to ketoacidosis in a few hours if not addressed in a timely manner.39 These complications, albeit rare, can be minimized by an active patient who performs ongoing monitoring.
Is an Insulin Pump Cost Effective?
Cost is a significant concern as insulin pumps can cost $2000-$8000 per pump and up to $300 per month for supplies. For people with commercial insurance or copays, this can amount to a substantial personal/insured cost. Despite this cost, evidence indicates that CSII is a cost-effective treatment option compared with MDI for children and adults with type 1 diabetes.40-42
The use of an insulin pump is a personal choice, and patients should be given the opportunity to evaluate all available options in the market before making their final decision. Factors to consider are management complexity, size, weight, appearance, available features, warranty, technical support, and cost.39
Starting Patients on an Insulin Pump
Typically, the discussion of using of an insulin pump begins when patients have trouble maintaining glucose control despite multiple daily insulin injections. Most insurance companies cover insulin pumps for patients with type 1 diabetes or advanced type 2 diabetes if there is evidence they no longer make endogenous insulin (as measured by a fasting c-peptide level and glucose). Physicians who treat a lot of patients with insulin pumps should assign a staff member to help with pump selection and patient training. If physicians do not treat a lot of patients who use insulin pumps, the pump companies generally will provide patient training to maximize patient satisfaction and safety. Ongoing pump adjustments will be made by experienced providers.
Insulin pump patients must be familiar with the use of multiple daily injections in case of mechanical failure. In addition, pump patients should always carry rapid-acting insulin pens and needles in case the insulin pump malfunctions.
How Do I Prescribe and Start a Patient on an Insulin Pump?
Insulin pumps are medical devices and will need insurance preapproval before being prescribed. (See Table 2.) Most insurance companies will cover insulin pump therapy for patients with type 1 diabetes, advanced type 2 diabetes in which the person no longer makes insulin, and gestational diabetes or pregnancy complicated by diabetes. To expedite coverage, physicians should complete the following steps. First, most insurance companies require documentation that patients have records of basal bolus insulin therapy, proof of diabetes education, and ability to do carbohydrate counting. In addition, physicians should show that patients are no longer making endogenous insulin by ordering a c-peptide in combination with a glucose level. The c-peptide is a measure of endogenous insulin production and should be low or undetectable in patients with type 1 diabetes or advanced type 2 diabetes (no longer making insulin). In addition, physicians should order a glucose test because insulin secretion is glucose dependent; if the glucose is low at the time of the lab draw, the normal physiologic response is to suppress insulin secretion. Patients with type 1 diabetes also need laboratory evidence of related autoimmunity, so physicians should order glutamic acid decarboxylase antibodies and islet cell antibodies. A positive response will usually provide evidence for coverage for an external insulin pump.
Table 2: Insulin Pumps Available in the United States
Manufacturer |
Pump Name |
Animas Corporation |
OneTouch Ping |
Asante Solutions |
Snap |
Insulet Corporation |
OmniPod |
Medtronic Diabetes |
MiniMed 530G MiniMed Paradigm |
Roche |
Accu-Chek Combo |
Sooil Development |
Dana Diabecare IIS |
Tandem Diabetes Care |
t:slim |
Although many insulin pumps are available, most have similar central functions. Most of the differences are related to patient preference or stylistic components. Pump manufacturers provide patients and families with information (via print literature and online) to help with pump selection. Some offices offer pre-pump classes to give patients a hands-on review of insulin pumps. Selecting a pump is a like selecting a car. Most cars serve the same practical function, but people have strong preferences of one brand over another. This is an important part of patient satisfaction.
Most patients can initiate the process of ordering a pump. Insurance companies usually require the physician to provide documentation that an insulin pump is appropriate for the individual patient. For optimal success, providers should be trained and experienced in using insulin pump therapy, and patients should meet the criteria listed in Table 3. Pump manufacturers can provide training for both providers and patients, and it is important that treating providers and support staff be central in the training of their patients on insulin pump therapy. In addition, providers who prescribe and use insulin pump therapy need to be able to provide support 24 hours per day, 7 days a week in case patients experience trouble with their pumps.
Table 3: CMS Guidelines for Insulin Pump Coverage25,43
U.S. Centers for Medicare & Medicaid Services (CMS) Insulin Pump Patient Eligibility Criteria |
Adapted from: Centers for Medicare & Medicaid Services. Decision Memo for Insulin Pump: C-Peptide Levels as a Criterion for Use (CAG-00092R). www.cms.gov. |
To be eligible for CMS insulin pump coverage, patients must meet one of the following criteria: (A) Patient has completed a comprehensive diabetes education program and has been receiving MDI insulin with frequent self-adjustments for at least 6 months before pump initiation. Patient has documented SMBG frequency an average of ≥ 4 times per day during the previous 2 months. Patient must also meet ≥ one of the following criteria:
|
(B) Patient on pump therapy before enrollment with a documented SMBG an average of ≥ 4 times per day during the month before enrollment. |
(C) Fasting C-peptide ≤ 110% lower limit of normal or ≤ 200% lower limit of normal if CrCl ≤ 50 mL/min with concurrent FPG ≤ 225 mg/dL; or beta-cell autoantibody positive |
Adhering to the following guidelines will help ensure patients have successful pump management.44 Patients should be able to:
- actively manage diabetes, including counting carbohydrates
- calculate insulin dose based on carbohydrates ingested
- calculate correction dose of insulin based on current and target glucose and sensitivity to insulin
- identify, prevent, and treat hypoglycemia
- adjust treatment to manage sick days
- problem solve when experiencing hyperglycemia.
Patients also must be able to manage the pump, including preparing, inserting, and changing the cannula and infusion set; utilize the pump to administer a bolus of insulin; suspend the pump and program a temporary basal rate; problem solve if there is a warning of a problem, and provide care to maintain the pump.
Problem Solving with Insulin Pumps
Patients who use insulin pump therapy must be able to resolve problems with their device. This requires ongoing active management and includes knowledge about changing infusion sites and reservoirs regularly, using the pump as intended, and managing pump alarms. Patients who are pumping need to keep backup supplies, such as quick-acting insulin pens, in case of pump failure. If the case of mechanical failure, patients should contact the pump company directly. Most companies will replace the pump within 24 hours. In addition, patients should contact their health care team for any other problems, such as unexpected hyperglycemia, problems with insulin delivered with no obvious mechanical failure, or an infected site.
The Future of Insulin Pump Therapy
While beyond the scope of this paper, continuous glucose monitoring devices can be linked to insulin pump therapy. Currently, only one company in the United States has a commercially available integrated system. However, most insulin pumps companies are working on this capacity. One pump in the United States has a sensor augmented system in which the pump will shut off for 2 hours if the glucose drops low.45 This technology has been shown to reduce the risk of severe hypoglycemia and nocturnal hypoglycemia with similar glucose-lowering effects.45,46
Manufacturers are constantly developing new technologies to improve insulin pumps. Researchers are designing artificial intelligence software to recognize glucose patterns and to alert patients and providers to possible needs for changes in basal or bolus doses. In the future, there likely will be simplified and more rapid data downloading and improved connectivity. Transmission of CGM and control of insulin infusion rates by small devices with remote displays and alarms also are in development.46,47 Smartphones will be able to act as data integrators to allow sharing of information from multiple meters, CGM, and pumps between patients and clinicians. Modified smartphones with built-in glucose testing and pump controllers are also in development.47
A recent study tested a "bionic" pancreas with a linked sensor and dual hormone (insulin and glucagon) pump for people with type 1 diabetes.48 This system improved glucose control and reduced hypoglycemia compared to current insulin pump therapy. With these advances, the future of insulin pump therapy appears to be very bright.
Summary
Insulin is an increasingly important component of diabetes treatment. The number of people requiring insulin is likely to rise dramatically in response to the pandemic of obesity facing our nation and the increased rates of type 2 diabetes. The use of insulin, with new more physiologic insulins and advanced delivery methods, can be effective and convenient across a wide profile of patients. With the continued development of "smarter" pumps, the management of one of the most common chronic conditions is becoming safer and more effective.
Acknowledgements: The authors would like to thank Samantha Shubrook, MA, for her extensive editorial assistance in this manuscript.
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