[The insulin analog, Humalog, in discontinuous: from pharmacology to clinical use]

Humalog is the first analog of human insulin to be evaluated on a large scale in clinical conditions by discontinuous subcutaneous administration. Eight international multicentric studies have investigated the efficacy and tolerance of Humalog in protocols with 3 daily insulin injections (3 preprandial injections of Humalog associated with 1 or 2 injections of Umuline NPH or Umuline Zinc). A total of 2834 patients participated in these studies, including 2,277 who used Humalog. In addition to these trials, more than 5,000 patients had used Humalog by 1996, in some cases for more than 3 years. In insulin-dependent diabetes (IDDM), glycaemic control at the time of inclusion of patients in these protocols, as evaluated by HbA1C, was generally moderate (8 to 9%) despite 3 daily injections. This did not constitute intensive care since basal insulin for half of these patients was ensured by only a single daily injection. In these conditions, the results obtained showing significant postprandial improvement in glycaemic control and a significant reduction of the number of hypoglycaemic episodes, particularly at night, are important even though HbA1C levels were not significantly decreased. In a more recent crossover study (1996), 199 well-controlled IDDM patients (HbA1C = 7.3%) were treated intensively by multiple injections. The number of severe hypoglycaemic episodes with coma was only one-fifth that of the group treated by Humalog (equivalent to a reduction of 26 comas per 100 patients/year) in the absence of any significant modification of HbA1C. No differences were noted for lipids, adverse side effects or severe events (except hypoglycaemic episodes) and immunogenicity. In non-insulin-dependent diabetes, the results were similar but less impressive concerning the improvement in postprandial glycaemic control and the reduction in hypoglycaemic episodes. In addition to the significant results obtained in these studies, Humalog was favoured by the vast majority of patients. It is likely that Humalog will allow intensified treatment of diabetes in very favourable conditions, and that more patients will achieve the difficult goal of normalising glycaemia. However, a single injection of NPH or prolonged insulin is not sufficient for that purpose. Two daily injections will generally be necessary.