An Overview of Insulin Breakthroughs

Diabetes Charts

Insulin therapy has come a long way from its introduction in 1922. The first insulin injection, which consisted of 15 mL of the substance and was described as "a thick brown muck," resulted in an expected drop in blood glucose - and an unexpected abscess at the injection site. Fortunately, today's options in insulin therapies offer treatment that is a far cry from the "muck" of 1922. More than 80 years later, technological advances have led to the development of insulin that is safe and effective with minimal to no pain.¹

Insulin for human use was originally derived from either beef or pork sources (see sidebar). In the 1980s, advancing scientific techniques and the use of recombinant DNA technology produced insulin that was derived from a human source and safe for human use. Even further recombinant DNA breakthroughs have allowed scientists to create insulin analogs.¹ These resulting products offer a myriad of alternative insulin preparations for superior glycemic control in diabetic patients.

Options in Insulin Therapy

Both type 1 and type 2 diabetic patients are candidates for insulin therapy. Its use in type 1 diabetes is usually straightforward: All type 1 diabetics, whose pancreatic ? islet cells are not producing insulin as a result of autoimmune damage, will require insulin therapy to replace what their body is unable to make. In type 2 diabetes, however, insulin therapy may not be as clear-cut. Unlike the insulin deficiency of type 1 diabetes, type 2 diabetes is characterized by insulin resistance and subsequently may lead to decreased insulin production. Although insulin therapy in type 2 diabetes has been shown to be effective, it usually is not first-line treatment.³

Despite the physiologic differences between type 1 and type 2 diabetes, insulin therapy in both conditions shares a common goal: to prevent hyperglycemia by supplying what the body can no longer produce. The insulin products available today have been designed to mimic the release of insulin in a healthy body.

In a healthy, nondiabetic patient, prandial insulin is the first phase of insulin release. It occurs as a response to glucose consumption, such as during a meal. In insulin therapy, prandial control is maintained by rapid-and short-acting insulins, which are given just prior to a meal. In a healthy body, postabsorptive blood glucose?especially glucose made by the liver?is controlled by endogenous basal insulin. Intermediate-and long-acting insulins are intended to offer basal control in insulin therapy.⁴

Rapid-acting Insulins

Three rapid-acting insulin preparations are available in the United States: insulin aspart (Novolog), insulin lispro (Humalog), and insulin glulisine (Apidra). Their onset of action is fast?occurring 5 to 15 minutes after administration?and they peak within 30 to 90 minutes. The overall duration of action of the rapid-acting insulins generally is less than 5 hours.^5,6

Rapid-acting insulins usually are administered 15 minutes prior to a meal. Because these insulins have such a fast onset and short duration, they have a decreased risk of postprandial hypoglycemia. Although the risk of hypoglycemia is lower, the risk still is present, and patients never should delay eating after using a rapid-acting insulin.^5,7

Short-acting Insulin

Regular insulin is considered short-acting insulin, because its onset, peak, and duration are appropriate for mealtime dosing but still are longer than those of the rapid-acting insulins. This insulin has an onset of 30 to 60 minutes, a peak of 2 to 3 hours, and a duration of 5 to 8 hours.

As with the rapid-acting insulins, patients using regular insulin should understand the importance of following insulin administration with a meal. Regular insulin is associated with a higher risk for postprandial hypoglycemia than are the rapid-acting agents.⁸

Intermediate-acting Insulin

With an onset of 2 to 4 hours, a peak of 4 to 10 hours, and a duration of 10 to 16 hours, Neutral Protamine Hagedorn (NPH) insulin is the most common intermediate-acting insulin in the United States today. It works as a basal insulin, and its use often is combined with a rapid-or short-acting insulin.^5,7,8

Lente insulin (Novolin L, Humulin L Lente) has offered another option for intermediate control. Although a residual supply of lente insulin still may be available, this product no longer is being manufactured and will not be available, once the supply is exhausted. Patients using lente insulin should be advised to contact their prescriber for an alternative intermediate-acting agent.^9,10

Long-acting Insulins

Long-acting insulins, such as insulin glargine (Lantus) and insulin detemir (Levemir), have an onset of 2 to 4 hours and a duration of 20 to 24 hours. These insulins are "peakless" and usually require a rapid-or short-acting insulin for prandial glucose control.^5,7,8

Some patients may have used ultralente (Humulin L Ultralente) insulin for long-acting control. Due to decreasing consumer demand and advancing technology, the manufacturer has discontinued production of ultralente. Patients still using ultralente should contact their prescriber to have their insulin changed to a commercially available long-acting agent.⁹

Inhaled Insulin

Inhaled insulin (Exubera) provides rapid-to short-acting insulin therapy in a needleless delivery system. Its onset of 10 to 20 minutes is similar to that of rapid-acting insulins, whereas its duration of 6 hours is closer to that of regular insulin. Inhaled insulin is approved for both type 1 and type 2 diabetes. In type 1 diabetes, inhaled insulin should be used in addition to a longer-acting insulin. In type 2 diabetes, inhaled insulin can be used either alone or in conjunction with oral or longer-acting insulin preparations.¹¹

Mixing It Up

Patients using both rapid-or short-acting and intermediate-acting insulin may prefer a single injection with a combination insulin product over giving themselves multiple injections. Several commercially available premixed insulins are available.

Humalog Mix 75/25 (75% insulin lispro protamine and 25% insulin lispro) and NovoLog Mix 70/30 (70% aspart protamine and 30% insulin aspart) are analog mixtures with onsets of 5 to 15 minutes and durations of 10 to 16 hours. For patients using human insulin, an alternate mixture is available that consists of 70% NPH and 30% regular insulin. It has on onset of 30 to 60 minutes and a duration of 10 to 16 hours. As with any rapid-or short-acting insulin, it is imperative that patients using these preparations never delay eating after administration of the insulin.^5,7

Some patients may require a more customized therapy but still want the convenience of a single injection. Patients mixing their own insulin always should check with their prescriber first. NPH insulin is compatible with regular insulin, insulin aspart, insulin glulisine, and insulin lispro. The rapid-or short-acting insulin always should be drawn into the syringe before the NPH, and the resulting mixture should be injected immediately. As always, a meal never should be delayed after the administration of any rapid-or short-acting insulin.^6,7,12 Insulin glargine and insulin detemir never should be mixed with any other products.^7,13

Patient Education

Insulin doses are highly patient-specific and depend on glucose levels, food consumption, exercise, and the use of additional hypoglycemic agents. Blood glucose monitoring is often recommended in insulin therapy. Patients using insulin should be aware of the signs and symptoms of both hypo-and hyperglycemia and the appropriate actions to take in both cases.¹²

All unopened injectable insulin preparations should be kept in the refrigerator and never should be frozen. Insulin vials or devices in use may be left at controlled room temperature (refer to manufacturer guidelines for product-specific room temperature expiration dates). Pharmacists should advise patients to inspect their insulin for changes in the solution's appearance or particulate matter prior to use. Inhaled insulin should be kept at controlled room temperature and never should be refrigerated or frozen.⁷

Diabetes management can appear overwhelming. Today's patients with diabetes have multiple therapies available to provide safe and effective blood glucose control. Awareness and education of both patients and providers can result in effective management of both type 1 and type 2 diabetes.

Dr. Holmberg is a pharmacist with Phoenix Children's Hospital, Phoenix, Ariz.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Rybovic, Pharmacy Times, Ascend Media Healthcare, 103 College Road East, Princeton, NJ 08540; or send an email request to: arybovic@ascendmedia.com