Insulin Detemir: A Long-Acting Insulin Product
Insulin Detemir: A Long-Acting Insulin Product
Purpose: The pharmacology, pharmacokinetics, efficacy and tolerability, safety, drug interactions, dosage and administration, cost, and place in therapy of insulin detemir are reviewed.
Summary: Insulin detemir is a long-acting, neutral, and soluble insulin analogue with a lower within-subject variability of fasting plasma glucose levels than isophane insulin human (NPH insulin) and insulin glargine. The lower within-subject variability of insulin detemir may decrease hypoglycemic events, especially nocturnal events, and may contribute to a decreased incidence of weight gain. In vivo, insulin detemir is 98-99% bound to albumin—one of the mechanisms contributing to its long duration of action. Several open-labeled, randomized, multicenter trials have been conducted comparing the safety and efficacy of insulin detemir to NPH insulin in patients with type 1 or type 2 diabetes mellitus. In most trials, patients were randomized to receive insulin on three different dosing schedules: basal insulin twice daily before breakfast and at bedtime, basal insulin at 12-hour intervals, or basal insulin before breakfast and dinner. Mealtime insulin was given as part of the basal-bolus therapy. Glycosylated hemoglobin values were similar in patients receiving insulin detemir or NPH insulin. Insulin detemir appears to be well tolerated. The most common adverse effects reported during clinical trials were hypoglycemia, headache, dizziness, and injection-site reactions.
Conclusion: Insulin detemir given once or twice daily as part of basal-bolus insulin therapy is at least as effective as NPH insulin in maintaining overall glycemic control in adult patients with type 1 or type 2 diabetes mellitus.
Diabetes mellitus affects a large portion of the U.S. population and carries a high rate morbidity and mortality for patients afflicted with the disease. Tight metabolic control achieved in part by the use of insulin is the key to preventing and delaying complications in patients with diabetes. Current American Diabetes Association guidelines recommend a goal glycosylated hemoglobin (HbA1c) of <7% in patients with diabetes and state that therapy should be reviewed or changed if values are consistently >8%. The first insulin product was brought to market in 1923 by Eli Lilly. In the 1930s protamine zinc insulin was introduced as the first long-acting insulin, which improved the care of patients with diabetes by reducing the number of daily injections a patient had to administer. The results of the Diabetes Control and Complications Trial in the 1990s demonstrated the importance of tight glycemic control and caused a resurgence of interest in long-acting insulins. Since that time, researchers have been trying to develop insulin products that mimic physiological insulin. Insulin glargine, a peakless insulin that allows providers to treat hyperglycemia with less incidence of hypoglycemia, received approved labeling from the Food and Drug Administration (FDA) in 2000 and has begun to replace older insulin products (e.g., isophane insulin human [NPH insulin], Ultralente). In June 2005, FDA approved the labeling for a new basal insulin with protracted action, insulin detemir (Levemir, Novo Nordisk). This article discusses the pharmacology, pharmacokinetics, efficacy and tolerability, safety, drug interactions, dosage and administration, cost, and place in therapy of insulin detemir.
Abstract and Introduction
Abstract
Purpose: The pharmacology, pharmacokinetics, efficacy and tolerability, safety, drug interactions, dosage and administration, cost, and place in therapy of insulin detemir are reviewed.
Summary: Insulin detemir is a long-acting, neutral, and soluble insulin analogue with a lower within-subject variability of fasting plasma glucose levels than isophane insulin human (NPH insulin) and insulin glargine. The lower within-subject variability of insulin detemir may decrease hypoglycemic events, especially nocturnal events, and may contribute to a decreased incidence of weight gain. In vivo, insulin detemir is 98-99% bound to albumin—one of the mechanisms contributing to its long duration of action. Several open-labeled, randomized, multicenter trials have been conducted comparing the safety and efficacy of insulin detemir to NPH insulin in patients with type 1 or type 2 diabetes mellitus. In most trials, patients were randomized to receive insulin on three different dosing schedules: basal insulin twice daily before breakfast and at bedtime, basal insulin at 12-hour intervals, or basal insulin before breakfast and dinner. Mealtime insulin was given as part of the basal-bolus therapy. Glycosylated hemoglobin values were similar in patients receiving insulin detemir or NPH insulin. Insulin detemir appears to be well tolerated. The most common adverse effects reported during clinical trials were hypoglycemia, headache, dizziness, and injection-site reactions.
Conclusion: Insulin detemir given once or twice daily as part of basal-bolus insulin therapy is at least as effective as NPH insulin in maintaining overall glycemic control in adult patients with type 1 or type 2 diabetes mellitus.
Introduction
Diabetes mellitus affects a large portion of the U.S. population and carries a high rate morbidity and mortality for patients afflicted with the disease. Tight metabolic control achieved in part by the use of insulin is the key to preventing and delaying complications in patients with diabetes. Current American Diabetes Association guidelines recommend a goal glycosylated hemoglobin (HbA1c) of <7% in patients with diabetes and state that therapy should be reviewed or changed if values are consistently >8%. The first insulin product was brought to market in 1923 by Eli Lilly. In the 1930s protamine zinc insulin was introduced as the first long-acting insulin, which improved the care of patients with diabetes by reducing the number of daily injections a patient had to administer. The results of the Diabetes Control and Complications Trial in the 1990s demonstrated the importance of tight glycemic control and caused a resurgence of interest in long-acting insulins. Since that time, researchers have been trying to develop insulin products that mimic physiological insulin. Insulin glargine, a peakless insulin that allows providers to treat hyperglycemia with less incidence of hypoglycemia, received approved labeling from the Food and Drug Administration (FDA) in 2000 and has begun to replace older insulin products (e.g., isophane insulin human [NPH insulin], Ultralente). In June 2005, FDA approved the labeling for a new basal insulin with protracted action, insulin detemir (Levemir, Novo Nordisk). This article discusses the pharmacology, pharmacokinetics, efficacy and tolerability, safety, drug interactions, dosage and administration, cost, and place in therapy of insulin detemir.