The DURAbility of Basal versus Lispro mix 75/25 insulin Efficacy (DURABLE) trial: comparing the durability of lispro mix 75/25 and glargine

Abstract

Objective: This study compared the durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25: 75% insulin lispro protamine suspension/25% lispro) and once-daily insulin glargine, added to oral antihyperglycemic drugs in type 2 diabetes patients.

Research design and methods: During the initiation phase, patients were randomized to LM75/25 or glargine. After 6 months, patients with A1C ≤ 7.0% advanced to the maintenance phase for ≤ 24 months. The primary objective was the between-group comparison of duration of maintaining the A1C goal.

Results: Of 900 patients receiving LM75/25 and 918 patients receiving glargine who completed initiation, 473 and 419, respectively, had A1C ≤ 7.0% and continued into maintenance. Baseline characteristics except age were similar in this group. Median time of maintaining the A1C goal was 16.8 months for LM75/25 (95% CI 14.0-19.7) and 14.4 months for glargine (95% CI 13.4-16.8; P = 0.040). A1C goal was maintained in 202 LM75/25-treated patients (43%) and in 147 glargine-treated patients (35%; P = 0.006). No differences were observed in overall, nocturnal, or severe hypoglycemia. LM75/25 patients had higher total daily insulin dose (0.45 ± 0.21 vs. 0.37 ± 0.21 units/kg/day) and more weight gain (5.4 ± 5.8 vs. 3.7 ± 5.6 kg) from baseline. Patients taking LM75/25 and glargine with lower baseline A1C levels were more likely to maintain the A1C goal (P = 0.043 and P < 0.001, respectively).

Conclusions: A modestly longer durability of glycemic control was achieved with LM75/25 compared with glargine. Patients with lower baseline A1C levels were more likely to maintain the goal, supporting the concept of earlier insulin initiation.

Trial registration: ClinicalTrials.gov NCT00279201.

Figures

Figure 1

Flow diagram of patients’ disposition. bid, twice daily; qd, once daily. *P = 0.048 between-group difference. †One further death related to pancreatic carcinoma occurred in the LM75/25 group after study discontinuation.

Figure 2

A: Time to failure of regimen to maintain A1C goal in patients receiving insulin lispro mix 75/25 (LM75/25) and glargine. B: A1C by visit. C: Percentage of patients maintaining the A1C goal at the end point within the LM75/25 treatment group by baseline A1C subgroup. D: Percentage of patients maintaining the A1C goal at the end point within the glargine treatment group by baseline A1C subgroup. The between-group comparison showed a significantly higher percentage of LM75/25-treated patients with a baseline A1C >10.0% maintained the A1C goal at the end point compared with glargine-treated patients with a baseline A1C >10.0% at the end point (P = 0.044). E: Percentage of patients maintaining A1C goal at end point within the LM75/25 treatment group by baseline BMI subgroup. F: Percentage of patients maintaining the A1C goal at the end point within the glargine treatment group by baseline BMI subgroup (between-group comparison showed significantly higher percentage of LM75/25-treated patients with baseline BMI 28–34 kg/m2 maintained A1C goal at end point compared with glargine-treated patients with baseline BMI 28–34 kg/m2 at end point, P < 0.001).