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Previous Volume 361:1736-1747 October 29, 2009 Number 18 Next

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ABSTRACT

Background Evidence supporting the addition of specific insulin regimens to oral therapy in patients with type 2 diabetes mellitus is limited.

Methods In this 3-year open-label, multicenter trial, we evaluated 708 patients who had suboptimal glycated hemoglobin levels while taking metformin and sulfonylurea therapy. Patients were randomly assigned to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Sulfonylurea therapy was replaced by a second type of insulin if hyperglycemia became unacceptable during the first year of the study or subsequently if glycated hemoglobin levels were more than 6.5%. Outcome measures were glycated hemoglobin levels, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain.

Results Median glycated hemoglobin levels were similar for patients receiving biphasic (7.1%), prandial (6.8%), and basal (6.9%) insulin-based regimens (P=0.28). However, fewer patients had a level of 6.5% or less in the biphasic group (31.9%) than in the prandial group (44.7%, P=0.006) or in the basal group (43.2%, P=0.03), with 67.7%, 73.6%, and 81.6%, respectively, taking a second type of insulin (P=0.002). Median rates of hypoglycemia per patient per year were lowest in the basal group (1.7), higher in the biphasic group (3.0), and highest in the prandial group (5.7) (P<0.001 for the overall comparison). The mean weight gain was higher in the prandial group than in either the biphasic group or the basal group. Other adverse event rates were similar in the three groups.

Conclusions Patients who added a basal or prandial insulin-based regimen to oral therapy had better glycated hemoglobin control than patients who added a biphasic insulin-based regimen. Fewer hypoglycemic episodes and less weight gain occurred in patients adding basal insulin. (Current Controlled Trials number, ISRCTN51125379 [controlled-trials.com] .)

Source Information

From the Diabetes Trials Unit (R.R.H., J.L.D., J.F.K., S.K.P.), Oxford Centre for Diabetes, Endocrinology and Metabolism (R.R.H., A.J.F., J.C.L., J.L.D., J.F.K., S.K.P.), and the Department of Primary Health Care and National Institute for Health Research School of Primary Care Research (A.J.F.), University of Oxford, Oxford; and the Department of Cardiovascular Sciences, University of Leicester, Leicester (M.J.D.) — both in the United Kingdom.

This article (10.1056/NEJMoa0905479) was published on October 22, 2009, at NEJM.org.

Address reprint requests to Dr. Holman at the Diabetes Trials Unit, OCDEM Churchill Hospital Headington, Oxford OX3 7LJ, United Kingdom, or at rury.holman{at}dtu.ox.ac.uk.

Full Text of this Article

This article has been cited by other articles:

• (2009). Comparison of Three Insulin Regimens. JWatch General 2009: 1-1 [Full Text]  
• (2009). All you need to read in the other general journals. BMJ 339: b4534-b4534 [Full Text]  
• Roden, M. (2009). Optimal Insulin Treatment in Type 2 Diabetes. NEJM 361: 1801-1803 [Full Text]