DURAbility of basal versus lispro mix 75/25 insulin efficacy (DURABLE) trial 24-week results: safety and efficacy of insulin lispro mix 75/25 versus insulin glargine added to oral antihyperglycemic drugs in patients with type 2 diabetes

Abstract

Objective: To compare the ability of two starter insulin regimens to achieve glycemic control in a large, ethnically diverse population with type 2 diabetes.

Research design and methods: During the initiation phase of the DURABLE trial, patients were randomized to a twice-daily lispro mix 75/25 (LM75/25; 75% lispro protamine suspension, 25% lispro) (n = 1,045) or daily glargine (GL) (n = 1,046) with continuation of prestudy oral antihyperglycemic drugs.

Results: Baseline A1C was similar (LM75/25: 9.1 +/- 1.3%; GL: 9.0 +/- 1.2%; P = 0.414). At 24 weeks, LM75/25 patients had lower A1C than GL patients (7.2 +/- 1.1 vs. 7.3 +/- 1.1%, P = 0.005), greater A1C reduction (-1.8 +/- 1.3 vs. -1.7 +/- 1.3%, P = 0.005), and higher percentage reaching A1C target <7.0% (47.5 vs. 40.3%, P < 0.001). LM75/25 was associated with higher insulin dose (0.47 +/- 0.23 vs. 0.40 +/- 0.23 units x kg(-1) x day(-1), P < 0.001) and more weight gain (3.6 +/- 4.0 vs. 2.5 +/- 4.0 kg, P < 0.0001). LM75/25 patients had a higher overall hypoglycemia rate than GL patients (28.0 +/- 41.6 vs. 23.1 +/- 40.7 episodes x pt(-1) x year(-1), P = 0.007) but lower nocturnal hypoglycemia rate (8.9 +/- 19.3 vs. 11.4 +/- 25.3 episodes x pt(-1) x year(-1), P = 0.009). Severe hypoglycemia rates were low in both groups (LM75/25: 0.10 +/- 1.6 vs. GL: 0.03 +/- 0.3 episodes x pt(-1) x year(-1), P = 0.167).

Conclusions: Compared with GL, LM75/25 resulted in slightly lower A1C at 24 weeks and a moderately higher percentage reaching A1C target <7.0%. Patients receiving LM75/25 experienced more weight gain and higher rates of overall hypoglycemia but lower rates of nocturnal hypoglycemia. Durability of regimens will be evaluated in the following 2-year maintenance phase.

Trial registration: ClinicalTrials.gov NCT00279201.

Figure 1

Flow of patients through the initiation phase (first 24 weeks) of the DURABLE trial.

Figure 2

A: Change in A1C from baseline to end point for patients treated with LM75/25 (■) versus glargine (□). **P < 0.01. B: A1C values at each visit for patients treated with LM75/25 (▲) versus glargine (□). **P < 0.01; †P < 0.001. C: Percent of patients achieving A1C target <7.0% at end point for patients treated with LM75/25 (■) versus glargine (□). †P < 0.001. D: Observed mean overall hypoglycemia rate (episodes · pt⁻¹ · year⁻¹) and TDI dose (units/kg) at each visit between 6 and 24 weeks of therapy for patients treated with LM75/25 (▲, hypoglycemia rate; △, TDI) or glargine (■, hypoglycemia rate; □, TDI).