NTDP Cohort 7
Title: “Three-Year Efficacy of Complex Insulin Regimens in Type 2 Diabetes”
Journal: The New England Journal of Medicine, vol. 361, no. 18, pages 1736-1747
Purpose: How do complex insulin regimens affect glycated hemoglobin, rate of
hypoglycemia and weight gain in type 2 diabetic patients?
Type 2 diabetes mellitus is often treated with metformin and an oral hypoglycemic agent (e.g. sulfonylurea); however, if this combination is not effective, insulin is often added to replace the oral hypoglycemic agent for better blood sugar control. In type 1 diabetes, intensive insulin therapy is designed to mimic normal insulin secretion as closely as possible.1 While the benefits of the combination of basal (long-acting) and prandial (bolus or fast-acting) insulin have been proven in type 1 diabetics, the best possible insulin regimen to be used in type 2 diabetics has not been established. By evaluating patients with type 2 diabetes with suboptimal glycemic control, the first phase of the Treating to Target in Type 2 Diabetes (4-T) study was designed to compare the clinical effects of adding biphasic, prandial, or basal analogue insulin. If glycated hemoglobin levels (HbA1C) were greater than 6.5% with a single type of insulin, the sulfonylurea therapy was replaced by a second type of insulin (complex regimen).
The first phase of the 4-T study was an open-label, multicenter, randomized three year trial including 708 patients who had suboptimal HbA1C levels (7-10%) while taking metformin and sulfonylurea therapy for at least 4 months. The study included men and women 18 years or older (mean age was 61.7 years), with a body-mass index of 40 or less, who had at least a 12 month history of type 2 diabetes. The participants were also required to inject insulin and perform self-monitoring of glucose. Patients were excluded for a previous history of thiazolinedione therapy, triple oral antidiabetic therapy, or insulin treatment.
The patients were randomly assigned to receive twice-daily biphasic insulin aspart (NovoMix 30®), three-times daily prandial insulin aspart (NovoRapid®), or once-daily (twice if required) basal insulin detemir (Levemir®). The biphasic and prandial insulin was injected subcutaneously before meals, and the basal insulin was injected subcutaneously at bedtime. Sulfonylurea therapy was replaced by a second type of insulin if glycemic control was not acceptable. Prandial insulin was added at midday to the biphasic-based regimen, basal insulin was added at bedtime to the prandial-based regimen, and prandial insulin was added at breakfast, lunch, and dinner for the basal-based regimen; these were the complex insulin regimens.
Patients were seen at 2, 6, 12, 24, 38, and 52 weeks during the first year, and every 3 months beyond the first year. The target range for preprandial blood glucose values was 72 to 99 mg/dL, and the target...