Practical approaches to insulin therapy for type 2 diabetes mellitus with premixed insulin analogues.
BACKGROUND
Insulin therapy may eventually be required to maintain glycemic control in many patients with type 2 diabetes mellitus. Premixed insulin analogues offer relatively physiologic and predictable time-action profiles and are available in more convenient delivery systems with finer needles than in the past. They also increase the convenience of administration with respect to mealtimes compared with premixed human insulin, and reduce the number of injections compared with basal-bolus therapy.


OBJECTIVE
This manuscript describes the development of premixed insulin analogues, reviews efficacy and safety data from randomized trials of premixed insulin analogues compared with human insulin 70/30 or basal insulins, and discusses their use for the management of type 2 diabetes.


METHODS
English-language randomized clinical trials comparing premixed insulin analogues with either premixed human insulin formulations or basal insulins for the treatment of type 2 diabetes, published through May 2005, were identified using PubMed. Pharmacokinetic and pharmacodynamic studies were also included. Abstracts presented at the meetings of the American Diabetes Association, International Diabetes Federation, and the European Association for the Study of Diabetes in 2003 and 2004 were also reviewed.


RESULTS
Premixed insulin analogues allow delivery of both basal and prandial insulin in 1 injection and are more convenient than premixed human insulin formulations. The rapid-acting component is absorbed and cleared more quickly, thereby allowing mealtime administration and providing better postprandial glycemic control. Although there is an increased risk of minor hypoglycemia, 3 comparative, randomized trials have shown that patients using premixed analogues twice daily are more likely to reach glycosylated hemoglobin (HbA(1c)) goals compared with those using only insulin glargine once daily. Premixed insulin analogues are available in vials, pens, and dosers.


CONCLUSIONS
Premixed insulin analogues have a more physiologic time-action profile, can be administered closer to mealtime, and produce greater reductions in the magnitude of postprandial glucose excursions than human insulin 70/30. Despite these advantages, no consistent differences in HbA(1c) reduction or the incidence of hypoglycemia versus human insulin 70/30 have been found in most short-term trials. Although there is an increased risk of minor hypoglycemia, patients using premixed insulin analogues twice daily are more likely to reach HbA(1c) goals than those using only insulin glargine once daily. Further studies are necessary to examine whether these advantages improve patient outcomes in clinical practice.
Rolla
Arturo R
AR
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. arolla@bidmc.harvard.edu
Rakel
Robert E
RE
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D019518:Postprandial Period; D016032:Randomized Controlled Trials as Topic
D007328:Insulin; D005947:Glucose