Insulin Therapy— Reducing Barriers, Overcoming Fears Insulin is a safe and effective treatment method to help patients manage type 2 diabetes By Jerry Meece, RPh, FACA, CDE

T

he burden that diabetes has placed on the health care system as a result of increased morbidity, mortality, and economic costs has continued to increase with each new decade. In 2005, diabetes prevalence in the United States grew to 20.8 million, representing 7 percent of the population. In 2002, cost estimates for diabetes care reached $132 billion and are projected to reach $156 billion by 2010. The disease will no doubt continue to present challenges. Economic studies have verified the value of good glycemic control in terms of reducing morbidity and mortality and improving quality of life (QOL). However, there is an important ally in treating diabetes—insulin. In particular for patients with type 2 diabetes, insulin is safe, effective, and the most potent drug available to achieve glycemic targets. Unfortunately, it is not used early enough, often enough, or aggressively enough to help patients to achieve glycemic goals that have been proven to reduce morbidity and mortality. Approximately five million people with diabetes in this country inject 20

america’s

Pharmacist | June 2006

insulin daily. Several studies point to the fact that this number is not as high as it should be due to reluctance of patients and providers to initiate insulin. Prior to the 32nd annual American Association of Diabetes Educators meeting in August 2005, an informal survey of diabetes educators identified the following barriers to starting insulin: • Patient resistance and fear • Needles and injections equated with pain • Complications (such as amputations or kidney failure) • Weight gain • Inconvenience • Physician resistance • Time-consuming • Inadequate support/resources • Lack of updated information • Cost www.ncpanet.org

The focus here will be on addressing these barriers, primarily looking at patient resistance, but also providing insight as to how diabetes educators can enhance communications between patients with type 2 diabetes and health care providers by promoting active self-management and reducing barriers to effective therapy.

Pharmacists taking an active role in diabetes education can help patients understand that the failure of therapy is not their fault, but is due to the progressive nature of the disease. The most important thing is to work together with the patient as a member of a diabetes care team to make sure that the treatment matches the disease’s pathophysiology, which may include insulin use.

Dispelling Myths

Needle Phobia

One of the major myths to be dispelled is that insulin should be used as a last resort, only when the patient has “failed” oral therapy. Too often, this results in poorly controlled patients who incur increased morbidity and mortality. However, it is well known that as time goes on, type 2 diabetes becomes more challenging to manage. Most patients with type 2 diabetes will eventually need to use insulin because of the natural course of the disease, a point that should be explained to patients in the initial stages of their treatment.

Many patients with type 2 diabetes have some degree of psychological insulin resistance (PIR), a term used to identify insulin initiation avoidance by patients. There is good reason to believe that providers may be affected just as much by PIR as patients, especially concerning type 2 diabetes. Causes of this may include economic as well as social issues, such as the stigma that needle use carries in society. Needle phobia is thought to be a significant reason for the delay in starting insulin by both providers and patients. People carry with them images of the first time

www.ncpanet.org

June 2006 | america’s Pharmacist

21

they saw a physician come at them with what looked like a 6-inch needle, and the fear they associated with these early events. From the first mention of insulin therapy, providers need to reassure patients that today’s needles are much finer compared to the past, are laser sharpened, and are silicone coated for ease of entry into the skin. Thus, the injection process is now one that many patients consider painless. The use of insulin-delivery systems such as pens can also help to minimize needle fear. Insulin pen devices have been developed to offer easier, safer, more accurate, and more discreet insulin injections. Their availability for various types of insulin products can improve patient acceptance and provide accurate and easier dosing than conventional syringes. The benefits of using insulin pens include accurate dosing, faster and easier injection times, increased patient acceptance and adherence, faster and easier ability to change dosage settings, and in some cases, automatic resetting of the dosing button after drug delivery in some devices. Pen needles are also sharper than standard insulin needles are, as they don’t go through the insulin vial stopper prior to injection. The newest method of delivering insulin, by inhalation, may also help address the fear of self-injection, and could lead to insulin being accepted more readily and used earlier in therapy. In January, 2006, the Food and Drug Administration’s approved the first ever inhaled insulin, Exubera, an inhaled powder form

of recombinant human insulin (rDNA) developed by Pfizer and Sanofi-Aventis for the treatment of adult patients with type 1 and type 2 diabetes. How much of an impact Exubera will have on adherence and earlier insulin use remains to be seen as it starts being used outside clinical trials. Inhaled insulin will not replace all insulin injections for patients with type 1 diabetes and in some patients with type 2 diabetes, because in all cases of type 1 and many cases of type 2, patients will still need long-acting insulins for basal control of blood sugars. The role of the pharmacist will become increasingly important as questions arise as to which therapy is best suited for each individual patient. An important role of the diabetes educator is to take the time to sit down with the patient and ask open-ended, nonjudgmental questions that help the patient address his or her concerns and aid in decision making in all areas of diabetes management. Addressing specific concerns and pointing out the advantages of getting blood glucose levels under control (such as more energy, fewer complications, and fewer trips to the bathroom at night), along with pointing out the advantages of insulin pen devices, can greatly reduce the degree of PIR.

Complication Fears Some cultures believe that starting insulin is the beginning

of the end, or that insulin is actually toxic. Obviously, these concerns will cause insulin therapy resistance. It is only by having conversations with the patient that this particular reason for resistance may reveal itself. Diabetes educators need to promote a culturally sensitive approach and to be aware of the patient’s perspective and opportunities for education and clarification. Several major studies have shown that good glycemic control (including the use of insulin) lowers complication risks. Recent studies have shown that tight control, such as that available with insulin therapy, reduced heart attacks and stroke by 57 percent. Put simply, tighter control means fewer complications over time. The best educators not only have the skills to understand complex studies such as these, but also have the ability to explain them in terms that can be easily understood by their patients.

Simplifying Insulin Initiation One of the barriers to the early and aggressive use of insulin is the belief, often held by clinician and patient alike, that starting insulin may be too complicated and too time-consuming. Diabetes educators can ameliorate this by becoming familiar with proven initiation and subsequent titration protocols and procedures for insulin use. Upon approval by the physi-

cian, printed titration schedules can be offered that empower patients to help manage their own insulin regimens. Delays in starting insulin for patients with type 2 diabetes may be due in part to uncertainty about how to best to make the transition from oral therapy to insulin. While there is no one “right” way to initiate insulin therapy, there are several options, depending on the patients’ preference, needs, and abilities. Recent studies provide evidence-based guidelines that present relatively clear guidance on treatment protocols. These studies show that when appropriate glycemic targets are chosen and a systematic titration of insulin dosage is agreed on by both the clinician and patient, several methods of initiating insulin may be successful.

Patient Convenience Patients are often concerned about the inconveniences and complexities, perceived or real, associated with insulin therapy. For patients using short-acting human regular insulin, these concerns can be valid. Human regular insulin, due to its slow onset of action, can create an adherence problem with patients who have to inject 30‑45 minutes before a meal. This requires the patient to know exactly what they will be eating for a meal that may or may not be served on time, and how the meal is prepared with regard to portion amounts that may or may

not equate carbohydrates consumed to insulin that has already been injected. You only have to consider the 30- to 45-minute countdown once regular insulin is injected for the patient to get to where they are going and to start eating to understand how difficult using regular insulin really is in real-life situations. Menu confusions, busy restaurants, traffic delays, and meetings running overtime are all part of the patient’s everyday life, and are often reasons patients are not doing well on regular insulin. Inject too early and hypoglycemia is a real problem. Inject too late and postprandial highs are followed by late postprandial hypoglycemic events. Rapid-acting insulin analogs or premixed insulin analogs delivered with insulin pens (or in pumps) offer a tremendous advantage to a patient’s ability to adhere to insulin regimens, regardless of lifestyle. With insulin pens, having the ability to carry a rapid-acting insulin, such as insulin lispro, insulin aspart, or insulin glulisine, in an injection device that is only slightly larger than an ink pen improves patient adherence. This is because the insulin can be injected immediately before meals, instead of the 30‑45 minute interval needed with regular human insulin, and because the pen delivery systems are more discreet and easy to carry.

Minimizing Therapy Side Effects Physicians and patients alike are often concerned about the side effects of insulin therapy. The two most often mentioned are hypoglycemia and weight gain.

Hypoglycemia Hypoglycemia is the most recognized adverse effect of intensive insulin therapy. Physicians familiar with the Diabetes Control and Complications Trial (DCCT) are aware that patients treated with intensive insulin therapy demonstrated a three-fold increase in the relative risk of an occurrence of severe hypoglycemia. In their own practices, they have seen similar results as tighter control is attempted by using insulin. Fears such as these and those based on studies such as the DCCT often create longer than necessary insulin initiation delays, causing greater loss of glycemic control. Fear of nocturnal hypoglycemia by both patient and provider was a major cause of nonadherence to the titration scheme in patients with type 2 diabetes enrolled in the Treat-to-Target study. Patients should be made aware that, although some degree of hypoglycemia may occur in as many as 30 percent of patients receiving insulin, severe hypoglycemia is rare and has been shown to affect only about 0.5 percent of patients with type 2 diabetes, a rate much lower than that seen in patients with type 1 diabetes. Hypoglycemia needs to be addressed early, and the role of the educator is integral in helping patients achieve glycemic goals by showing them how to recognize, treat, and avoid this problem. Patients should have a good understanding of not only 24

america’s

Pharmacist | May 2006

Symptoms and Causes of Hypoglycemia Signs of hypoglycemia • Shakiness,

light-headedness irritability

• Nervousness, • Confusion • Hunger • Tachycardia • Sweaty,

headachy

• Weak • Numbness

or tingling in tongue or lips

Causes of hypoglycemia • More

physical activity than usual that are too small, delayed or skipped • Excessive use of alcohol • Meals

the general symptoms of hypoglycemia, such as hunger, perspiration, nervousness, and confusion, but also the individual initial symptoms that may help prevent more severe hypoglycemia episodes from occurring. Symptoms and causes of hypoglycemia are summarized in the box above. Hypoglycemia symptoms and severity vary from person to person. Helping patients to understand and be aware of the earliest hypoglycemia symptoms allows these events to be easily managed with a snack or another glucose source. Patients should also be made aware of the difference between major and minor hypoglycemia and how to manage each. Major hypoglycemia is defined as an episode in which the patient requires assistance or treatment and, if inadequately treated, may be life threatening. In contrast, minor hypoglycemia refers to episodes that can be self-treated by consuming fast-acting carbohydrates. It is important to note that major hypoglycemia should be treated as an emergency. Glucagon injection kits are available for the emergency treatment (administered by family members) of major hypoglycemia, because patients with major hypoglycemia are usually unconscious or very confused and sleepy. It is important for the educator to positively frame the message as hypoglycemia is discussed. Explaining to them that while it is true that the risk of minor hypoglycemia rises as the patient progresses closer toward to A1C goals, the benefits of lower A1C levels far outweigh concerns about minor hypoglycemia episodes. The guiding principle for hypoglycemia avoidance when initiating insulin is for both educator and physician to “start low and go slow.” This means titrating upward as both patient and health care provider gain confidence through more frequent blood glucose monitoring regarding insulin requirements needed when combined with the individual’s lifestyle.

Weight Gain Weight gain is a common side effect of insulin therapy. Weight gain associated with improved glycemic control was evident in www.ncpanet.org

the DCCT, which studied patients with type 1 diabetes. It was also evident to a lesser degree in the United Kingdom Prospective Diabetes Study (UKPDS), which monitored patients with type 2 diabetes. In the UKPDS, five patients taking insulin gained 4 kg (8 lb, 13 oz) more than those treated with diet therapy over 10 years. Weight gain may come from several sources. With improved glycemic control, it may be due to decreased glycosuria, resulting in more glucose absorption and therefore more calories retained. Fluid retention has also been cited as a possible cause. Another factor is when patients eat more in an effort to treat or prevent hypoglycemia or perceived hypoglycemia that is associated with intensive treatment. The educator should do a thorough review of the patient’s blood glucose log to discuss insulin doses if, in fact, hypoglycemia is occurring. There should also be a discussion to ensure that the patient is not over treating hypoglycemia by overeating, instead of correctly matching carbohydrate intake to the severity of the reaction. Additionally, it can be seen that with improvement in daily blood glucose levels, patients often feel they have the ability to “cheat” on their meal plans more often. The benefits of good glycemic control on reducing the risk of diabetic complications through the appropriate use of intensive therapy should prevail over concerns for weight gain. To minimize this risk, patients starting on insulin should be seen by a dietitian who can help match food choices with insulin dosing, along with explaining special efforts they can make regarding diet and exercise to keep weight gain to a minimum. The use of insulin analogs as opposed to human insulin may reduce weight gain. Patients with type 2 diabetes treated with insulin aspart 70/30 had significantly less weight gain compared with those treated with human premix insulin (0.05 versus 2 kg). In the Treat-to-Target Trial, insulin glargine was associated with less weight gain than was NPH insulin. The new long-acting insulin analog, insulin detemir, has been shown to be associated with less weight gain than NPH in patients with type 2 diabetes. Recently, the combination of metformin and insulin has been shown to be associated with weight loss. This seems to be mostly due to a decrease in food intake (anorexic effect) that was associated with the use of metformin.

Cost Concerns Although insulin is associated with the most profound effects on A1C levels, there is always a concern about the cost of additional or new therapy. The addition of a third oral antidiabetes drug (OAD) to a patient with high A1C values on two OADs is unlikely to bring them to target if their A1C value is greater than 9 percent, as oral therapy is generally able to lower A1C only less than 2 percent. While any amount of insulin will lower A1C values in this patient, it may add to the cost depending on the insulin regimen. A fair comparison can be achieved only if a www.ncpanet.org

true cost-effectiveness analysis is performed. A cost analysis over a nine-month period in 1,177 patients with type 2 diabetes who were switched from oral medications to insulin found that, although insulin initiation increased health care costs by 10 percent during the initial post-insulin period, subsequent health care expenditures were reduced by 40 percent over the remainder of the nine-month period following insulin initiation. Another recent study compared the cost, efficacy, and safety of metformin and human insulin 70/30 with that of a triple oral regimen in patients who had an inadequate response to two OADs (A1C greater than 8 percent). Human insulin 70/30 plus metformin was as effective as three OADs in lowering A1C and fasting plasma glucose (FPG) values. The triple oral regimen was not as cost effective, and a high percentage of patients did not complete this regimen because of a lack of efficacy or adverse effects. Results showed that human insulin 70/30 and metformin cost $3.20 per day, compared with $10.40 per day for three OADs. Another factor to consider is that with a large portion of patients with diabetes having prescription cards with various copays (depending on the tier or level of copayment that a drug has in the prescription benefit plan), the amount of copayment saved by using insulin versus three OADs could be significant. A closer look at the oral regimen of every patient who is not achieving control is warranted, depending on the type of oral medication(s) used. Insulin might not only be more cost effective but also may help achieve better glycemic outcomes.

Team Approach Needed Diabetes is a complex, progressive, and highly individualized disease. To achieve the glycemic control required to avoid the serious complications that may occur from chronic hyperglycemia, a comprehensive team effort is required. Patients can achieve glycemic control when the diabetes management team recommends appropriately intensive therapies, provides diabetes self-management training, and assists patients in understanding the value of their individualized therapy. Insulin should now be viewed as a valuable therapeutic tool for early intervention that allows patients to attain and maintain target levels of blood glucose control. There are now published guidelines providing several options for the initiation of insulin therapy, including a choice of products and a choice of schedules. Furthermore, while there are many ways to implement insulin therapies, the one that the patient understands and agrees to is likely to be the most effective treatment.  Jerry Meece, RPh., FACA, CDE, is owner and director of Clinical Services at Plaza Pharmacy and Wellness Center in Gainesville, Texas, and head of the legislative unit of public affairs for the American Association of Diabetes Educators. He can be reached at 940-665-8401, or at [email protected]. June 2006 | america’s Pharmacist

25