The DURABLE trial study design: comparing the safety, efficacy, and durability of insulin glargine to insulin lispro mix 75/25 added to oral antihyperglycemic agents in patients with type 2 diabetes

Abstract

Background: While studies have compared the safety and efficacy of starter insulin regimens in type 2 diabetes, none have evaluated regimen durability (length of time a patient can maintain glycemic control) or the safety and efficacy of subsequent intensification regimens in a large, multinational cohort.

Methods: The DURABLE (Assessing the DURAbility of Basal vs Lispro Mix 75/25 Insulin Efficacy) trial will compare the ability of glargine once daily vs lispro mix 75/25 (75% insulin lispro protamine suspension, 25% lispro) twice daily added to oral antihyperglycemic agents to achieve and maintain hemoglobin A1c (HbA1c) goals. This randomized, open label, parallel study will enroll over 2000 insulin-naïve patients with type 2 diabetes from 11 countries, ages 30 to 80, with HbA1c >7.0% on at least two oral antihyperglycemic agents. At the completion of the 6-month initiation phase, safety and efficacy of the two regimens will be compared. Patients who achieve an HbA1c < or =7.0% at 6 months will continue into the 24-month maintenance phase to evaluate durability. In a substudy, patients not achieving HbA1c < or =7.0% at 6 months may be randomized to one of two intensification comparisons: patients previously on glargine will receive lispro mix 75/25 twice daily or basal/bolus therapy (glargine + thrice-daily mealtime lispro) and patients previously on lispro mix 75/25 will receive lispro mix 50/50 (50% insulin lispro protamine suspension, 50% lispro) thrice daily or basal/bolus therapy.

Results: Upon completion, this trial will provide new information about starter insulin durability, defined as the length of time patients can maintain HbA1c control (HbA1c < or =7.0%, or >7.0% but with an increase of <0.4% from the most recent HbA1c < or =7.0%). Additionally, the study will provide comparative data on HbA1c, blood glucose profiles, 1,5-anhydroglucitol, hypoglycemic episodes, weight change, and insulin dose for starter insulin regimens following 6 and 24 months of treatment, as well as intensified insulin via the 6-month substudy.

Conclusion: This trial aims to broaden clinicians' understanding of the ability of starter insulin and insulin intensification regimens to achieve and maintain glycemic control in patients with type 2 diabetes.

Keywords: Humalog® Mix 50/50; Humalog® Mix 75/25; basal bolus therapy; durability; durable; glargine; lispro.

Figures

Figure 1.

DURABLE study design. Solid lines identify design and timing of the initiation and maintenance phases of the primary study. Dotted lines identify design and timing of the two substudy arms.