Drugs 2005; 65 (3): 325-340

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325 1. Physiology of Insulin Secretion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326 2. Conventional Insulin Preparations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 3. Insulin Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328 3.1 Rapid-Acting Insulin Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328 3.1.1 Insulin Lispro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328 3.1.2 Insulin Aspart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329 3.1.3 Insulin Glulisine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329 3.1.4 Clinical Utility of Rapid-Acting Insulin Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 330 3.2 Premixed Insulins and Insulin Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 3.3 Basal Insulin Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 3.3.1 Insulin Glargine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 3.3.2 Insulin Detemir . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 3.3.3 Clinical Utility of Long-Acting Insulin Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 4. Insulin Analogues and Potential Mitogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334 5. In-Hospital Use of Insulin Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 6. Future Directions in Insulin Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336 7. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 Insulin is one of the oldest and best studied treatments for diabetes mellitus. Abstract Despite many improvements in the management of diabetes, the nonphysiological time-action profiles of conventional insulins remain a significant obstacle. However, the advent of recombinant DNA technology made it possible to overcome these limitations in the time-action profiles of conventional insulins. Used as prandial (e.g. insulin lispro or insulin aspart) and basal (e.g. insulin glargine) insulin, the analogues simulate physiological insulin profiles more closely than the older conventional insulins. If rapid-acting insulin analogues are used in the hospital, healthcare providers will need a new mind-set. Any error in coordination between timing of rapid-acting insulin administration and meal ingestion may result in hypoglycaemia. However, guidelines regarding in-hospital use of insulin analogues are few. The safety profile of insulin analogues is still not completely established in long-term clinical studies. Several studies have shown conflicting results with respect to the tumourigenic potential of this new class of agents. The