Análogos de insulina: en búsqueda del reemplazo fisiológico

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Translated abstract

Insulin analogues, developed by molecular engineering, have structural changes in the A and B insulin chains. These modifications change their action profile, rendering insulin replacement closer to physiology. Rapid acting analogues like lispro, aspart and glulisine, are absorbed rapidly from the subcutaneous tissue to the circulation. In addition, two long acting insulin analogues have been developed: glargine and detemir. The combination of a long acting insulin, to maintain baseline levels, and multiple daily doses of a rapid acting analogue are the mainstay of basal-bolus therapy. Multiples studies have compared human insulin (NPH and regular) with insulin analogues in patients with type 1 or 2 diabetes mellitus, showing an improvement in the metabolic control, fewer hypoglycemic events and better quality of life. In summary, insulin analogues offer new therapeutic options and allow an individualized intensive treatment

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Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

(1998)

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Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro.

M Lepore, S Pampanelli, C Fanelli … (2000)

To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients were studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U x kg(-1) x 24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of IV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1.5 +/- 0.3 h) (P 150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a flat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.