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Intensive Glucose Control and Complications in Type 2 Diabetes.

Two long-awaited reports from the U.K. Prospective Diabetes Study (UKPDS) shed light on the question of whether good control of type 2 diabetes with intensive treatment helps to reduce complications. In UKPDS 33, 3,867 patients (median age, 54 years) with newly diagnosed type 2 diabetes (fasting plasma glucose [FPG] between 108 and 270 mg/dl after three months dieting) were randomized to either intensive or conventional treatment. The intensive group received sulfonylurea (chlorpropamide, glyburide [glibenclamide], or glipizide) or insulin sufficient to keep FPG below 108 mg/dl. The conventional group received diet advice; drugs were added only if needed to keep FPG below 270 mg/dl or for symptomatic hyperglycemia.

During a 10-year follow-up, median HbA _1c was 7.0 percent in the intensive group and 7.9 percent in the conventional group. The intensive group had a significant 12 percent reduction in total diabetes-related endpoints (e.g., cardiovascular, peripheral vascular, eye, and renal), mainly due to fewer microvascular events, especially retinal photocoagulation. In addition, the intensive group had 10 percent fewer diabetes-related deaths (including deaths from MI and stroke) and 6 percent lower all-cause mortality, but these reductions were not statistically significant. The intensive group had significantly more hypoglycemic episodes and greater weight gain.

UKPDS 34 focused on 1,704 overweight patients, many of whom were also part of the UKPDS 33 analysis. Intensive treatment with metformin was compared with conventional treatment, and a secondary analysis compared metformin with chlorpropamide, glyburide, and insulin. Compared with the conventional group, the metformin group had significant reductions of 32 percent, 42 percent, and 36 percent in the three endpoints. Moreover, compared with the other intensive groups, the metformin group had fewer diabetes-related endpoints and less weight gain and hypoglycemia.

Comment: The message seems to be that intensive therapy in type 2 diabetes reduces diabetes-related -- and especially microvascular -- events. Whether reductions in macrovascular events and mortality will become significant with further follow-up is unclear. Finally, the authors suggest that metformin might be considered as a first-line drug for obese patients.

— B Jarman

Published in Journal Watch General Medicine October 2, 1998

Citation(s):

UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998 Sep 12 352 837-853.

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UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998 Sep 12 352 854-865.

• Medline abstract (Free)

Nathan DM. Some answers, more controversy, from UKPDS. Lancet 1998 Sep 12 352 832-833.

• Medline abstract (Free)