Superiority of insulin analogues versus human insulin in the treatment of diabetes mellitus.

The modern goals of insulin replacement in Type 1 and Type 2 diabetes mellitus (T1, T2DM) are A1C <6.5% long-term, and prevention of hypoglycaemia (blood glucose, BG <70 mg/dl). In addition to appropriate education and motivation of diabetic subjects, the use of rapid- and long-acting insulin analogues, is critical to achieve these goals. The benefits of rapid-acting analogues (lispro, aspart and glulisine have similar pharmacodynamic effects) compared with non-modified human regular insulin, are: (a) lower 1- and 2-h post-prandial blood glucose; (b) lower risk of late post-prandial hypoglycaemia (and therefore lower BG variability); (c) better quality of life (greater flexibility in timing and dosing of insulin). In T1DM, rapid-acting analogues improve A1C only by the extent to which replacement of basal insulin is optimized at the same time, either by multiple daily NPH administrations, or continuous subcutaneous insulin infusion (CSII), or use of the long-acting insulin analogues glargine or detemir. In T2DM, rapid-acting analogues reduce post-prandial hyperglycaemia more than human regular insulin, but systematic studies are needed to examine the effects on A1C. The benefits of long-acting insulin analogues glargine and detemir vs. NPH, are: (1) lower fasting BG combined with lower risk of hypoglycaemia in the interprandial state (night); (2) lower variability of BG. Glargine and detemir differ in terms of potency and duration of action. Detemir should be given twice daily in the large majority of people with T1DM, and in a large percentage of subjects with T2DM as well, usually at doses greater vs those of the once daily glargine. However, when used appropriately for individual pharmacokinetics and pharmacodynamics, glargine and detemir result into similar effects on BG, risk of hypoglycaemia and A1C. Rapid- and long-acting insulin analogues should always be combined in the treatment of T1 and T2DM.