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Keywords:

  • clinical trial;
  • diabetes;
  • insulin analogue;
  • insulin detemir;
  • treat-to-target;
  • TITRATETM

Aims:  To compare efficacy and safety of two fasting plasma glucose (FPG) titration targets [4.4–6.1 mmol/l (80–110 mg/dl) and 3.9–5.0 mmol/l (70–90 mg/dl)] using a patient-directed, treat-to-target algorithm for once-daily basal insulin in insulin-naïve subjects with type 2 diabetes suboptimally treated with oral antidiabetes drugs (OADs).

Methods:  In this 20-week, randomized, controlled, open-label, multicentre, treat-to-target study, 244 insulin-naïve subjects with type 2 diabetes, HbA1c≥7.0 and ≤9.0% on OAD treatment, were randomized (1 : 1) to one of two treatment arms using 3.9–5.0 or 4.4–6.1 mmol/l FPG as titration targets. Once-daily insulin detemir doses were adjusted using algorithm-guided patient-directed titration to achieve target FPG values.

Results:  Overall, the combined treatment groups achieved a mean HbA1c level of 6.9% at the end of the study. Substantial reductions in HbA1c were seen in both treatment groups, with the majority of subjects in both titration groups at the end of the study achieving the American Diabetes Association (ADA)-recommended HbA1c level of <7%. In the 3.9–5.0 mmol/l FPG target treatment group, HbA1c values decreased from a baseline mean of 8.0% to 6.8% at 20 weeks. In the 4.4–6.1 mmol/l FPG target group, HbA1c values decreased from 7.9% at baseline to 7.0% at 20 weeks (Intention to treat - last observation carried forward data set). These decreases were significantly different between the two treatment groups (Least squares mean difference = −0.271, 95% CI −0.441 to −0.101, p = 0.0019), favouring the FPG target of 3.9–5.0 mmol/l vs. the 4.4–6.1 mmol/l target. At the end of the study period, 64.3% of subjects in the 3.9–5.0 mmol/l treatment group achieved HbA1c levels <7% compared with 54.5% of subjects in the 4.4–6.1 mmol/l group (95% CI 1.03–3.37, odds ratio 1.86, p = 0.04). Insulin detemir dosing patterns were similar between treatment groups, with the 3.9–5.0 mmol/l group using slightly greater doses throughout the study period (0.57 U/kg vs. 0.51 U/kg at the end of the study). Overall rates of hypoglycaemia episodes were low and were comparable between treatment groups (7.73 and 5.27 events/subject/year for the 3.9–5.0 and 4.4–6.1 mmol/l groups, respectively). A single event of major hypoglycaemia was reported in the 3.9–5.0 mmol/l group. Mean weight changes from baseline to the end of the study were small and did not differ significantly between treatment groups.

Conclusions:  The 3.9–5.0 mmol/l FPG target showed superior efficacy compared with the 4.4–6.1 mmol/l target, although both FPG titration targets resulted in substantial reductions of HbA1c in patients with type 2 diabetes using a patient-directed insulin titration algorithm. A majority of subjects in both titration groups achieved the ADA-recommended guideline of <7% HbA1c at the end of the study with low rates of hypoglycaemia. These data indicate that lowering the fasting glucose target using a self-directed titration algorithm with once-daily detemir is safe and increases the likelihood of achieving the target level of HbA1c. Indeed, using this approach, a majority of patients can achieve an HbA1c of <7%.