Holman RR et al. (2007) Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med 357: 1716–1730

Various insulin regimens are used to treat patients with type 2 diabetes mellitus that is inadequately controlled by oral antidiabetic therapy. However, few studies have compared insulin regimens. Holman et al. reported interim results of a 3 year, open-label, randomized, controlled, multicenter trial comparing the efficacy and safety of adding biphasic, prandial or basal insulin to oral therapy for these patients.

Patients (n = 708) who had suboptimal glycemic control while receiving maximally tolerated doses of metformin and sulfonylurea were randomly allocated to additional treatment with twice-daily biphasic insulin aspart (n = 235), thrice-daily prandial insulin aspart (n = 239) or once-daily (or twice-daily if required) basal insulin detemir (n = 234). The study was completed by 222, 222 and 224 patients in the biphasic, prandial and basal insulin groups, respectively.

The mean HbA1c level at 1 year was lower in the biphasic and prandial insulin groups than in the basal insulin group (7.3%, 7.2% and 7.6%, respectively); however, only a minority of patients in each group (17.0%, 23.9% and 8.1%, respectively) achieved a target level of ≤6.5% at 1 year. Despite the superior performance of biphasic and prandial insulin in lowering HbA1c, both regimens were associated with an increased risk of hypoglycemia and greater weight gain as compared with the basal insulin regimen.

The findings suggest that many patients may benefit from more-complex insulin regimens; the authors will examine this hypothesis in the next 2 years of their trial.