• Diabetes & Endocrinology Clinical Trials
• Insulin
• Hyperglycemia/Hypoglycemia
• Diabetes Mellitus

• Diabetes & Endocrinology Clinical Trials
• Insulin
• Endocrinology
• Diabetes & Metabolic Syndrome
• Hyperglycemia/Hypoglycemia
• Diabetes Mellitus

A long-acting basal insulin glargine formulation, 300 U/mL (Gla-300), controlled glycemia as well as insulin glargine 100 U/mL (Gla-100) in patients with type 2 diabetes mellitus (T2DM) but with less nocturnal hypoglycemia. Matthew C. Riddle, MD, Oregon Health & Science University, Portland, Oregon, USA, presented findings from a Phase 3 multicenter, open-label study comparing the two insulin glargine formulations in patients with T2DM who were using basal plus mealtime insulin.

Gla-100 is a widely used basal insulin with no pronounced peak of action and a duration of action of ∼24 hours; it causes less hypoglycemia than human neutral protamine Hagedorn (NPH) insulin [Riddle MC et al. Diabetes Care 2003]. The investigational insulin glargine (Gla-300) contains the same molecule as Gla-100 but in a lower volume. It has a flatter and more prolonged pharmacokinetic and pharmacodynamics profile than Gla-100 [Jax T et al. EASD 2013 (abstr 1029)]. Whether or not the differences in pharmacokinetics between Gla-100 and Gla-300 translate into a clinical benefit is being tested in a worldwide series of Phase 3 studies in several populations of patients with type 1 diabetes mellitus and T2DM. The data presented here from the Comparison of a New Formulation of Insulin Glargine With Lantus in Patients With Type 2 Diabetes Mellitus on Basal Plus Mealtime Insulin [EDITION I; NCT01499082] were the first from this series of Phase 3 trials.

Adults (n=807) with T2DM on a basal-bolus insulin regimen that included at least 42 U/day of basal glargine or NPH insulin were randomized to 6 months of open-label treatment with either Gla-300 or Gla-100 once daily in the evening while continuing mealtime insulin. The basal insulin was titrated weekly to achieve a fasting plasma glucose of 80 to 100 mg/dL. Mealtime insulin dosage was not systematically titrated, with adjustments made at investigators' discretion only for safety reasons.

Subjects' mean age was 60 years, their mean duration of diabetes was 15.8 years, and their mean body mass index was 36.6 kg/m². More than half of the patients were using metformin. On entry, the mean basal insulin dose was 0.67 U/kg/day and the mean total insulin dose was 1kg/day. The mean baseline HbA1C level was 8.16%.

The primary endpoint, the change in HbA1C from baseline to Month 6, was −0.83% in both the Gla-100 and Gla-300 groups, the 0.0% difference met the criterion for noninferiority of Gla-300. There were no differences between the treatments in other glycemic control outcomes.

The chief secondary endpoint was percentage of people with ≥1 severe or confirmed episodes of nocturnal hypoglycemia from Month 3 to Month 6. Fewer people assigned to Gla-300 experienced severe or confirmed nocturnal hypoglycemia during Months 3 to 6 (36.1% vs 46.0%, representing a 21% reduction in relative risk; p=0.0070). The occurrence of any hypoglycemic event during study period was numerically lower in the Gla-300 group than in the Gla-100 group.

There were no between-treatment differences in weight change, adverse events, serious adverse events, adverse events causing withdrawal, injection-site reactions, and mortality.

Dr. Riddle concluded that in patients with T2DM who require high-dose basal-bolus insulin therapy, Gla-300 was as effective as Gla-100 in blood glucose control and was associated with a reduction in severe or confirmed nocturnal hypoglycemia.

• © 2013 MD Conference Express®