Intermediate and long-acting insulins: a review of NPH insulin, insulin glargine and insulin detemir

Headnote

Key words: Glycemic control - Hypoglycemia - Insulin analogs - Insulin deterair - Insulin glargine - Long-acting insulins

ABSTRACT

Objective: To review intermediate- and long-acting insulins with specific emphasis on the newer insulin analogs.

Methods: A MEDUNE search, in English, was conducted with a cut-off of June 30, 2006, using the terms 'NPH insulin', 'insulin analogs', 'insulin glargine', 'insulin detemir' and 'long-acting insulins'. All clinical trials from within the search period were included.

Results: The insulin analogs, insulin glargine and Insulin detemir, were introduced in an attempt to improve glycemic control among patients with diabetes, without Increasing the risk of hypoglycemia. This review indicates that both Insulin analogs demonstrate better glycemic control than NPH insulin, based on measurements of HbA^sub 1c^, fasting glucose and infra-subject variability in blood glucose. This was accomplished with similar or reduced risk of hypoglycemia. Also, insulin detemir appears to be associated with less body weight increase than NPH insulin or insulin glargine.

Conclusion: The newer long-acting insulin analogs, insulin detemir and glargine, appear to provide better glycemic control than NPH insulin without increasing the risk of hypoglycemia.

Introduction

A number of different studies over the last two decades, most notably The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), have unequivocally demonstrated that tight metabolic control can not only reduce the incidence, but also delay the development of late complications in patients with type 1 and type 2 diabetes, respectively1-6. Unfortunately, the intensive insulin therapy required to achieve tight glucose control is associated with a significantly increased risk of developing hypoglycemia4. To some extent, this can be attributed to the pharmacokinetic/pharmacodynamic properties of traditional human insulin preparations4. It is well known that the traditional intermediateacting human insulin preparation, Neutral Protamine Hagedorn (NPH) insulin, exhibits a pronounced insulin peak 5-7 h after injection, resulting in increased risk of nocturnal hypoglycemia when injected in the evening, and has a duration of action that is too short to maintain glycemic control throughout the night7. In addition, it is well documented that the action of NPH insulin is often variable, in particular due to inadequate resuspension prior to injection as well as dissolution of crystals8,9. Finally, traditional short-acting regular human insulin has a slower onset, necessitating injection...