Aggressive Diabetes Management: Insulin as a Front-Line Drug

Pharmacy Times
Volume 0

Several landmark trials report that controlling diabetes with insulin therapy reduces the risk of diabetes-related microvascular complications.

Ms. Sloane is a freelance writer based in Jamesville, New York.

The traditional approach to managing type 2 diabetes is a stepwise process. It begins with lifestyle modification, followed by oral antidiabetics, and finally insulin therapy. More recently, glucagon-like peptide agents and pramlintide have been added to the ever-growing arsenal of diabetes medications.

Several landmark trials have established that controlling diabetes with insulin therapy reduces the risk of diabetes-related microvascular complications, such as retinopathy and neuropathy. For example, one such study found that intensive insulin therapy for 6 years reduced the risk of cardiovascular disease during long-term followup.1 In addition, an older, better-known study, the United Kingdom Prospective Diabetes Study, showed that a 1% reduction in mean A1C correlated with a 21% reduced risk for complications related to diabetes, including death.2

ADA Standard of Care

These studies and other pertinent statistics have resulted in a newer standard of care recommendation from the American Diabetes Association (ADA).3 This standard of care includes insulin as a front-line drug, rather than a last-resort treatment. This new protocol puts insulin as a recommended treatment when lifestyle modification and metformin fail to reach A1C goals, and it recognizes the advent of newer insulin analogs that closely mimic the body?s own insulin secretion.

Since basal insulin and postprandial excursions contribute to overall glycemic control, both fasting blood sugars and postprandial blood glucose should be targeted when trying to meet A1C goals. This is best accomplished with basal-bolus or multiple daily injection (MDI) insulin therapy. This includes long-acting insulin for background or basal insulin combined with a rapidacting insulin analog 15 minutes before meals.

Currently, 3 options for basal insulin therapy are available: neutral protamine Hagedorn (NPH), insulin glargine (Lantus), and insulin detemir (Levemir). Although more expensive than NPH insulin, insulin glargine and insulin detemir may be associated with fewer episodes of hypoglycemia and improved overall control, due to the absence of the peak seen with NPH insulin. NPH generally also must be given twice daily, due to a shorter duration of action. An advantage of NPH insulin is that it can be mixed with regular insulin in the same pen or syringe and may therefore be more convenient for some patients.

Basal-bolus insulin therapy with insulin glargine or insulin detemir, coupled with a rapid-acting insulin analog, allows for more freedom and flexibility for patients. Meals and snacks can be skipped or delayed more easily because patients can determine when they wish to eat.

Three available insulin analogs are considered rapid acting; that is, they start working within 15 minutes after eating. These insulins are aspart (NovoLog), glulisine (Apidra), and lispro (Humalog). Because basal or background insulin is being used, the rapidacting insulin is only needed when food is consumed or as a correction bolus for a random high blood sugar.

Patient Education Is Essential

This type of basal-bolus insulin therapy is the most effective way to get blood sugars under tight control because it most closely mimics the normal pancreas physiology. It is important to note that patient education is very important with this therapy, and it requires frequent blood sugar testing to be effective.

Generally, blood sugars need to be tested at least 4 times daily and oftentimes more. Interpretation of these blood sugars and knowing when to test is of utmost importance. For example, morning blood sugars are important to determine if the basal insulin is providing adequate coverage. If morning blood sugars are high, the dose of basal insulin is generally increased until a target blood sugar is achieved. The patient?s health care team provides target blood sugar ranges, and the ranges vary depending on the patient?s age and ability.

When dosing bolus or rapid-acting insulin, the size of the meal and type of food consumed must be considered. This is accomplished by counting the carbohydrate content of a snack or meal and dosing insulin accordingly. A good way to find an insulin-to-carbohydrate ratio is the rule of 500: divide the number 500 by a patient?s total daily insulin dose. The number you obtain will equal how many grams of carbohydrate will be covered by 1 unit of insulin. This is a starting point for dosing bolus insulin, but will vary depending on exercise, insulin resistance, and other prescription medications. Steroids, for example, will cause an increase in blood glucose, and more insulin is usually given if a patient is on prednisone or a similar product.

Insulin Pumps

Another option for aggressive treatment of patients with diabetes who do not like the idea of MDIs is to use an insulin pump. In simple terms, an insulin pump is a device with a reservoir for insulin that has an internal computer that can be programmed very specifically for a basal rate; a small amount of insulin gets released from the reservoir via tubing that gets attached by a small catheter into an area like the stomach. Every few minutes, small amounts of rapid-acting insulin are slowly pulsed out, and these rates can be changed every hour based on the individual. For mealtime or bolus insulin, the patient matches his or her carbohydrate intake to insulin?just like MDI?and pushes a bolus button on the pump when meals are eaten. This is a simplified version of pump therapy, and many companies and variations are available for patients to choose from.


With all of the current evidence to support the use of insulin in the patient with type 2 diabetes, it should not take long for the physician to initiate insulin therapy. Many studies demonstrate that early use of insulin can help patients meet A1C goal, improve beta cell function, and decrease the probability of future complications from this insidious disease.


  • 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-dependant diabetes mellitus. N Engl J. Med. 1993;329:977-986.
  • UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet.1998;352:837-853.
  • American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28(suppl 1):S4-S36.

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