Efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the U.K. Prospective Diabetes Study (UKPDS 57)
- Alex Wright, FRCP1,
- A.C. Felix Burden, FRCP2,
- Richard B. Paisey, FRCP3,
- Carole A. Cull, PHD4,
- Rury R. Holman, FRCP4 and
- for the U.K. Prospective Diabetes Study Group
- 1University Hospital, Birmingham, U.K.
- 2University Hospitals of Leicester, Leicester, U.K.
- 3Torbay Hospital, Torquay, Devon, U.K.
- 4Diabetes Trials Unit, OCDEM, University of Oxford, Oxford, U.K.
OBJECTIVE—To evaluate the efficacy of the addition of insulin when maximal sulfonylurea therapy is inadequate in individuals with type 2 diabetes.
RESEARCH DESIGN AND METHODS—Glycemic control, hypoglycemia, and body weight were monitored over 6 years in 826 patients with newly diagnosed type 2 diabetes in 8 of 23 U.K. Prospective Diabetes Study (UKPDS) centers that used a modified protocol. Patients were randomly allocated to a conventional glucose control policy, primarily with diet (n = 242) or an intensive policy with insulin alone (n = 245), as in the main study. However, for patients randomized to an intensive policy with sulfonylurea (n = 339), insulin was added automatically if the fasting plasma glucose remained >108 mg/dl (6.0 mmol/l) despite maximal sulfonylurea doses.
RESULTS—Over 6 years, ∼53% of patients allocated to treatment with sulfonylurea required additional insulin therapy. Median HbA1c in the sulfonylurea ± insulin group was significantly lower (6.6%, interquartile range [IQR] 6.0–7.6) than in the group taking insulin alone (7.1%, IQR 6.2–8.0; P = 0.0066), and significantly more patients in the sulfonylurea ± insulin group had an HbA1c <7% (47 vs. 35%, respectively; P = 0.011). Weight gain was similar in the intensive therapy groups, but major hypoglycemia occurred less frequently over all in the sulfonylurea (± insulin) group compared with the insulin alone group (1.6 vs. 3.2% per annum, respectively; P = 0.017).
CONCLUSIONS—Early addition of insulin when maximal sulfonylurea therapy is inadequate can significantly improve glycemic control without promoting increased hypoglycemia or weight gain.
- C, conventional glucose control policy
- CI, chlorpropamide ± insulin
- FPG, fasting plasma glucose
- GI, glipizide ± insulin
- IQR, interquartile range
- SI, sulfonylurea ± insulin
- UKPDS, U.K. Prospective Diabetes Study
Address correspondence and reprint requests to Dr. Carole A. Cull, Diabetes Trials Unit, Radcliffe Infirmary, Woodstock Rd., Oxford OX2 6HE U.K. E-mail:.
Received for publication 15 March 2001 and accepted in revised form 9 October 2001.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.