Clinical question: When added to oral diabetic agents, which insulin regimen (biphasic, prandial or basal) best achieves glycemic control in patients with Type 2 diabetes?
Background: Most patients with Type 2 diabetes mellitus (DM2) require insulin when oral agents provide suboptimal glycemic control. Little is known about which insulin regimen is most effective.
Study design: Three-year, open-label, multicenter trial.
Setting: Fifty-eight clinical centers in the United Kingdom and Ireland.
Synopsis: The authors randomized 708 insulin-naïve DM2 patients (median age 62 years) with HgbA1c 7% to 10% on maximum-dose metformin or sulfonylurea to one of three regimens: biphasic insulin twice daily; prandial insulin three times daily; or basal insulin once daily. Outcomes were HgbA1c, hypoglycemia rates, and weight gain. Sulfonylureas were replaced by another insulin if glycemic control was unacceptable.
The patients were mostly Caucasian and overweight. At three years of followup, median HgbA1c was similar in all groups (7.1% biphasic, 6.8% prandial, 6.9% basal); however, more patients who received prandial or basal insulin achieved HgbA1c less than 6.5% (45% and 43%, respectively) than in the biphasic group (32%).
Hypoglycemia was significantly less frequent in the basal insulin group (1.7 per patient per year versus 3.0 and 5.5 with biphasic and prandial, respectively). Patients gained weight in all groups; the greatest gain was with prandial insulin. At three years, there were no significant between-group differences in blood pressure, cholesterol, albuminuria, or quality of life.
Bottom line: Adding insulin to oral diabetic regimens improves glycemic control. Basal or prandial insulin regimens achieve glycemic targets more frequently than biphasic dosing.
Citation: Holman RR, Farmer AJ, Davies MJ, et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med. 2009;361(18):1736-1747.