In a pivotal trial comparing the safety and efficacy of the long-acting analog insulin Lantus(R) (insulin glargine [rDNA origin] injection) with NPH (neutral protamine Hagedorn) in patients with type 2 diabetes, previously treated with insulin alone, Lantus demonstrated a 25 percent lower risk of nocturnal hypoglycemia.

The study, published in the April issue of Diabetes Care, stated that the lower risk of nocturnal hypoglycemia may reflect the smooth, continuous release profile of Lantus compared with the peak of NPH, which can result in maximum concentrations of insulin at night when NPH is given at bedtime. Severe hypoglycemia was observed in only one (0.4 percent) Lantus patient versus six (2.3 percent) NPH insulin patients (P=0.0581). Prior to enrollment in the study, patients had been treated with long-acting insulin with or without short-acting insulin.

Lantus is indicated for once-daily subcutaneous administration at bedtime in the treatment of adult patients with type 2 diabetes or adult and pediatric patients (ages 6 and above) with type 1 diabetes who require basal (long-acting) insulin for the control of hyperglycemia.

Method

This 59-center, randomized, open-label comparison of Lantus and NPH, enrolled 518 patients with type 2 diabetes, ages 40-80, who had been receiving NPH insulin treatment (with or without regular insulin for postprandial control) for more than three months. Because Lantus is a clear solution and can easily be distinguished from NPH insulin visually, an open-label design was required. In this study, patients were randomized to receive either Lantus (n=259) once-daily or NPH insulin (n=259) once or twice daily for 28-weeks. Doses were adjusted to obtain target fasting glucose of <6.7 mmol/l. At the end of the study, the median total daily insulin dose in both treatment groups was 0.75 IU/kg.

Results

Lantus was associated with 25 percent reduction in nocturnal hypoglycemia during the treatment period following the dose-titration phase (26.5 percent vs. 35.5 percent, P=0.0136). Patients in the Lantus group also experienced less weight gain than those in the NPH group (0.4 kg vs 1.4 kg, P=0.0007).

The treatment groups showed similar improvements in HbA1c, after patients began with an average baseline HbA1c of approximately 8.5 percent. The treatments also were associated with similar reductions in fasting glucose levels and overall mild symptomatic hypoglycemia was similar in Lantus patients (61.4 percent) and NPH patients (66.8 percent).

Lantus(R) (insulin glargine [rDNA origin] injection) Information

The adverse events commonly associated with Lantus include the following: hypoglycemia, lipodystrophy, skin reactions (such as injection-site reaction, pruritus, rash) and allergic reactions. Sodium retention and edema may also occur with the use of any insulin therapy.

In clinical studies in adult patients there was a higher incidence of treatment-emergent injection-site pain (2.7 percent Lantus versus 0.7 percent NPH). The reports of pain at injection site were usually mild and did not result in discontinuation of therapy.

Hypoglycemia is the most common adverse effect of insulins, including Lantus. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes. Any change of insulin should be made cautiously and only under medical supervision.

Lantus must not be diluted or mixed with any other solution. If mixed or diluted, the solution may become cloudy, and the onset of action/time to peak effect may be altered in an unpredictable manner.

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