New insulin analogs for the treatment of diabetes developed over the past decade can simplify insulin dosing regimens and improve flexibility for patients. Good diabetes control often requires the use of insulin, which may preserve beta-cell function and improve lipid metabolism and survival after myocardial infarction. DeWitt and Hirsch searched MEDLINE for all English-language articles involving insulin use in adult patients with type 1 and type 2 diabetes. The researchers found that many trials were designed poorly and were sponsored by pharmaceutical companies, and concluded that expert clinical practice is far ahead of research.
In reviewing the types of insulin, the authors identify rapid-acting insulin (such as insulin lispro and insulin aspart), short-acting regular insulin, intermediate-acting neutral protamine Hagedorn (NPH) insulin and Lente insulin, and long-acting insulin (such as Ultralente insulin and insulin glargine). Hypoglycemia is the major adverse effect of insulin therapy, with the majority of episodes occurring nocturnally. Intensive therapy with insulin increases a patient's risk of severe hypoglycemia. Another adverse effect of insulin therapy is weight gain, which can be decreased with bedtime administration of insulin. Retinopathy can worsen with rapid improvement in glycemic control.
Multiple injections with prandial insulin (used before meals) gives patients greater lifestyle flexiblility. NPH and regular insulin provide basal and prandial effects. For this reason, preventing midmorning hypoglycemia and ensuring a timely lunch are important aspects of glycemic management. A short-acting or rapid-acting insulin supplement should be used to correct hyperglycemia. In patients with type 2 diabetes, the authors recommend 1 U of supplemental insulin for each 30 mg per dL (1.7 mmol per L) above the target glucose level.
Insulin supplementation between meals is more complicated because of the potential for “insulin stacking,” or accumulation of insulins. Physicians should consider starting insulin therapy in patients whose hemoglobin A1c approaches 8 percent despite optimal therapy. Patients often require dosages of greater than 100 U per day to achieve optimal therapy. The use of metformin with insulin may be the best combination regimen, because it typically results in less weight gain and fewer hypoglycemic episodes. The combination of sulfonylureas and insulin becomes ineffective in patients whose A1c level approaches 10 percent. NPH and glargine can be adjusted easily based on fasting nocturnal glucose levels. Glargine may result in fewer nocturnal hypoglycemic episodes and less weight gain, but it costs twice as much as NPH. If nocturnal hypoglycemia cannot be controlled and glargine cannot be used, the patient can use prandial lispro in combination with sulfonylureas. In patients having difficulty achieving daytime control, premixed insulin regimens at the same insulin dosage can be helpful. Lunchtime prandial insulin should be added, and the morning insulin dose should be decreased accordingly.
The authors conclude that limited data suggest that using insulin may be cost-effective by reducing the complications of diabetes. They add that an efficient diabetes care team is often lacking, especially in the primary care setting.