Insulin Lispro

Summary Abstract Insulin lispro, alone (Humalog®) or as premixture (Humalog Mix25® or Humalog Mix50®) is indicated for the treatment of hyperglycaemia in diabetes mellitus in many countries worldwide. It is a recombinant human insulin analogue and, except for the transposition of two amino acids, is identical to endogenous human insulin. Insulin lispro has a faster onset of action and shorter duration of activity than regular human insulin, and the time-action profile of insulin lispro mimics that of the physiological response of endogenous human insulin to food intake. In diabetic patients, from young children to the elderly, it has demonstrated postprandial blood glucose control similar to or better than that achieved with regular human insulin, without an increased risk of hypoglycaemia. In some trials, the risk of hypoglycaemia, including nocturnal episodes, was less in insulin lispro recipients than in regular human insulin recipients. Insulin lispro alone, or as a premixture with the longer-acting insulin neutral protamine lispro, can be administered immediately before or after meals. This convenient and flexible injection schedule may enable patients, including those with a non-routine lifestyle or unpredictable eating or exercising habits, to achieve the tight glycaemic control required to minimise long-term complications of diabetes and contributes to patient satisfaction with treatment. Pharmacologica Properties Insulin lispro is a recombinant human insulin analogue that is equipotent on a molar basis to regular human insulin with respect to hypoglycaemic activity, but with a faster onset of action, an earlier peak and a shorter duration of action. The blood glucose profile achieved with insulin lispro indicates that the optimal time of administration of insulin lispro is within 15 minutes before ingestion of a meal, but it can also be administered immediately or shortly after a meal. As a result of its shorter duration of action, insulin lispro is associated with lower postprandial, but higher postabsorptive and preprandial blood glucose levels, than regular human insulin, resulting in similar overall glycaemic control for the two insulins. Commercially available premixtures of 25% insulin lispro and 75% insulin neutral protamine lispro (insulin lispro Mix25) and 50% of each (insulin lispro Mix50) have been shown to provide better 24-hour or mealtime glycaemic control than mixtures of human regular insulin with neutral protamine Hagedorn (NPH) insulin. The incidence of specific or cross-reacting insulin antibodies in patients with type 1 or type 2 diabetes treated with insulin lispro was similar to that in patients treated with recombinant regular human insulin. Therapeutic Efficacy In patients with type 1 diabetes receiving insulin, intensive premeal administration of insulin lispro reduced mean 2-hour postprandial glucose levels relative to a similar regular human insulin-based regimen, but fasting or preprandial blood glucose levels were generally similar for the two insulins. Overall, long-term glycaemic control (as assessed by glycosylated haemoglobin [HbA 1c ] values) was essentially similar for the two insulins. The risk of hypoglycaemia was not greater with insulin lispro than with regular human insulin and was significantly lower in some trials. Insulin lispro was also effective in the treatment of type 2 diabetes. In patients with early type 2 disease who had not previously used insulin, insulin lispro prompted a significantly greater reduction from baseline in mean overall 2-hour postprandial blood glucose excursions than glibenclamide (glyburide). The addition of insulin lispro to an oral antihyperglycaemic or NPH insulin regimen was effective at improving or regaining blood glucose control (reducing postprandial blood glucose and HbAic values) in patients with secondary oral antihyperglycaemic treatment failure. Patients with type 2 diabetes who were already receiving insulin therapy had 2-hour postprandial blood glucose levels or blood glucose excursions with insulin lispro that were generally significantly lower than with regular human insulin. Glycaemic control (HbAic values) and the incidence of hypoglycaemic episodes did not generally differ significantly between the insulin lispro and the other treatment groups in these trials. Premixed insulin lispro achieved glycaemic control in patients with either type of diabetes that was similar to that with self-mixed insulin lispro and NPH insulin, or premixed or self-mixed regular human insulin and NPH insulin, with a generally similar risk of hypoglycaemia. In patients with type 2 diabetes, insulin lispro Mix25 twice daily and insulin lispro Mix50 three times daily demonstrated greater efficacy (significantly lower HbA 1c values and postprandial blood glucose levels) than insulin glargine (a long-acting insulin) at bedtime. Twice-daily insulin lispro Mix25 demonstrated similar efficacy to twice-daily biphasic insulin aspart. In patients (including the elderly) with type 2 diabetes who had been previously inadequately controlled on a sulfonylurea, glycaemic control was significantly better with insulin lispro Mix25 than with oral glibenclamide, although the rate of hypoglycaemic episodes tended to be higher in the group receiving insulin than in the glibenclamide group. The administration of insulin lispro delivered as a continuous subcutaneous insulin infusion (CSII) using an external pump, relative to the administration of insulin lispro as multiple daily injections, improved glycaemic control (and at a lower insulin dose and with fewer hypoglycaemic episodes) in patients with type 1 diabetes, and achieved similar glycaemic control in elderly patients with type 2 diabetes. Comparing insulins delivered as a CSII, insulin lispro achieved similar or better glycaemic control than that achieved with regular human insulin and achieved similar glycaemic control to that achieved with insulin aspart. Insulin lispro as a CSII has also been successfully used in children. Children receiving insulin lispro achieved postprandial blood glucose levels that were similar to or lower than those achieved with regular human insulin, with similar overall glycaemic control and risk of hypoglycaemia. Adolescents receiving insulin lispro experienced significantly lower postprandial blood glucose levels and a lower rate of hypoglycaemia than recipients of regular human insulin, but overall glycaemic control was similar for both groups. Prospective and retrospective studies in pregnant women with diabetes indicate that glycaemic control and maternal and fetal outcomes with insulin lispro therapy were generally similar to those with regular human insulin and in line with data available for other insulins. In large crossover trials, patients with type 1 diabetes using insulin lispro preferred the flexibility and convenience and were more satisfied with their treatment than patients using regular human insulin. Trials in patients with type 2 diabetes indicated that there was no difference in treatment satisfaction between insulin lispro and regular human insulin, but the use of insulin lispro mixtures was preferred over that of glibenclamide. Tolerability The tolerability of rapid-acting insulins is essentially concerned with hypoglycaemia. The largest trials in adult patients with type 1 or 2 diabetes receiving insulin lispro demonstrated significantly lower rates of hypoglycaemia, including nocturnal episodes, in insulin lispro recipients than in regular human insulin recipients. In almost all the other trials, the incidence of hypoglycaemia in insulin recipients of all ages was similar to or less than that in regular human insulin or other comparator insulin recipients.