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Review of Insulins

Insulin, the cornerstone of therapy for type 1 diabetes mellitus, is also frequently utilized in type 2 diabetes mellitus. While some insulin products require a prescription for purchase, the NPH and regular varieties (excluding 500 u/mL regular) may be purchased without a prescription in many states.

While it has gone unnoticed by many, the insulin market has changed in the past few years! Manufacturers have ceased making insulins de-rived from pork. Additionally, Lilly has stopped manufacturing Lente and Ultralente insulins. Have no fear, however. A variety of new insulins has hit the market. While not all are contained on the Cabell Huntington Hospital formulary, it is important for providers to recognize these new insulins and know their role in diabetic management. Below is a review of different insulin products categorized by onset of action. Bolded products are on formulary at Cabell Huntington Hospital.

Rapid Acting Insulins

Rapid acting insulins are typically used to combat postprandial hyperglycemia. There are three pro-ducts available; the newest being Apidra (insulin glulisine). All of these products are made from recombinant DNA technology and are administered subcutaneously. The biggest distinction within this subclass results from changes in the amino acid sequence of the molecules that allows for different onset of actions and peak effects. This influences the timing of the insulin with respect to meals.

Humalog (insulin lispro) has an onset of action of approximately 15-30 minutes, peaks between 30-150 minutes and can last up to 6.5 hours. It is typically administered within 15 minutes prior to mealtime or immediately after a meal.

NovoLog (aspart insulin) has an onset of action of approximately 10-20 minutes, peaks between 60-180 minutes and can last up to 5 hours. It is typically administered 5-10 minutes prior to meals.

Apidra (insulin glulisine) has an onset of action of approximately 10-15 minutes, peaks between 60-90 minutes and can last up to 5 hours. It is typically administered 15 minutes prior to mealtime or within 20 minutes of beginning a meal.

Short Acting Insulins

Both Humulin R and Novolin R are "regular" insulins with similar pharmacokinetic profiles. Both have an onset of action of approximately 30-60 minutes, peak between 60 and 300 minutes and can last up to 8 hours. This form of insulin can be administered intravenously as well as subcutaneously. Typically regular insulin must be administered 30 minutes prior to meals.

Intermediate Acting Insulins

Intermediate insulins are administered twice daily to meet daily basal insulin requirements. They are typically two-thirds of the total daily insulin requirements. These are often termed "NPH." All NPH products currently on the market are human products; Iletin II NPH, an older form, was derived from pork but is no longer available. One of the limitations to NPH insulin is its peak during early morning hours, which might lead to the Somogyi effect.

NPH insulin can be drawn up into the same syringe as rapid acting or regular insulins. When doing so, remember the phrase "fast first" meaning that the quicker acting insulin should be drawn up first, and then the NPH insulin can be added to the syringe.

Humulin N and Novolin N are both isophane insulin suspensions that contain zinc or protamine to help delay their action. These insulins have an onset of action of approximately 60-120 minutes, peak between 6 to 14 hours and can last up to 24 hours, though a duration of action of 16 hours is more likely. NPH is typically administered twice daily before breakfast and bedtime. It can only be given subcutaneously. Additionally, these products are both available in vials and in cartridges for use with insulin pens.

Long Acting Insulins

Long acting insulins are also utilized for basal insulin requirements. While the may require less frequent administration, they typically are much more costly for patients. An advantage to long-acting insulins is the lack of a definite peak response. These products are for subcutaneous administration only. Neither of the long-acting insulins can be mixed with other insulins.

Lantus (insulin glargine) has an onset of action of approximately 60 minutes, and can last up to 24 hours. It is typically administered once daily at bedtime. Insulin glargine may cause pain at the injection site due to its low pH of 4. However, it is this low pH that gives insulin glargine its long duration of action. When the medication is injected into subcutaneous tissue with a pH of ~7.4, a microprecipitate is formed from which small amounts of the medication are released over time.

Levemir (insulin detemir) uses its ability to bind to albumin as its slow release mechanism. Therefore, it will have its maximum effect starting 6-8 hours after the injections. The relative flat action profile results in a duration of action up to 24 hours, although this is dose dependent with larger doses having a longer duration of action. Insulin detemir can be administered once or twice daily; daily doses should be administered with dinner or at bedtime. The time-action of insulin detemir is less variable than NPH insulin and may allow for better glycemic control.

Combination Insulin Products

There are currently five different combination products available: Novolog 70/30 (70% insulin aspart protamine and 30% insulin aspart), Humalog 75/25 (75% insulin lispro protamine and 25% insulin lispro), Humulin 70/30 and Novolin 70/30 (both 70% NPH and 30% regular), and Humulin 50/50 (50% NPH and 50% regular). These products may be utilized to maximize therapy while limiting the number of injections the patient uses daily. However, tight control is often difficult with these products due to their fixed ratios.

Inhaled Insulin Products

This year, a breakthrough in insulin therapy occurred with the announcement from the FDA of the approval of Exubera, a dry powder regular (short acting) insulin for inhalation. The insulin particles are one to three microns in size and are absorbed into the alveolar capillary bloodstream.

Exubera is indicated for the treatment of type 1 diabetes mellitus in combination with long-acting insulin products. It is also indicated for the treatment of type 2 diabetes mellitus, either as monothearpy or in combination with oral hypoglycemic medications or long-acting insulin.

While an inhaled insulin product is exciting, it does have some limitations. First, it is supplied in blisters that contain either 1 or 3 mg of product which corresponds to approximately 3 and 8 units of insulin, respectively. Note that three 1 mg capsules are not equivalent to one 3 mg capsule. Thus, very specific equivalent doses of subcutaneous insulin cannot be delivered with this product. Additionally, it is contraindicated in patients who are currently smoking or have smoked in the past six months, and in those with unstable or poorly controlled lung disease, including those with chronic obstructive pulmonary disease. Due to its ability to worsen pulmonary function, the manufacturer recommends obtaining pulmonary function tests at baseline, six months and annually thereafter for patients using the medication.