mystery.txt

Intensive blood-glucose control with sulphonylureas or insulin compared with
      conventional treatment and risk of complications in patients with type 2 diabetes
BACKGROUND: Improved blood-glucose control decreases the progression of diabetic 
      microvascular disease, but the effect on macrovascular complications is unknown. 
      There is concern that sulphonylureas may increase cardiovascular mortality in
      patients with type 2 diabetes and that high insulin concentrations may enhance
      atheroma formation. We compared the effects of intensive blood-glucose control
      with either sulphonylurea or insulin and conventional treatment on the risk of
      microvascular and macrovascular complications in patients with type 2 diabetes in
      a randomised controlled trial. METHODS: 3867 newly diagnosed patients with type 2
      diabetes, median age 54 years (IQR 48-60 years), who after 3 months' diet
      treatment had a mean of two fasting plasma glucose (FPG) concentrations of
      6.1-15.0 mmol/L were randomly assigned intensive policy with a sulphonylurea
      (chlorpropamide, glibenclamide, or glipizide) or with insulin, or conventional
      policy with diet. The aim in the intensive group was FPG less than 6 mmol/L. In
      the conventional group, the aim was the best achievable FPG with diet alone;
      drugs were added only if there were hyperglycaemic symptoms or FPG greater than
      15 mmol/L. Three aggregate endpoints were used to assess differences between
      conventional and intensive treatment: any diabetes-related endpoint (sudden
      death, death from hyperglycaemia or hypoglycaemia, fatal or non-fatal myocardial 
      infarction, angina, heart failure, stroke, renal failure, amputation [of at least
      one digit], vitreous haemorrhage, retinopathy requiring photocoagulation,
      blindness in one eye, or cataract extraction); diabetes-related death (death from
      myocardial infarction, stroke, peripheral vascular disease, renal disease,
      hyperglycaemia or hypoglycaemia, and sudden death); all-cause mortality. Single
      clinical endpoints and surrogate subclinical endpoints were also assessed. All
      analyses were by intention to treat and frequency of hypoglycaemia was also
      analysed by actual therapy. FINDINGS: Over 10 years, haemoglobin A1c (HbA1c) was 
      7.0% (6.2-8.2) in the intensive group compared with 7.9% (6.9-8.8) in the
      conventional group--an 11% reduction. There was no difference in HbA1c among
      agents in the intensive group. Compared with the conventional group, the risk in 
      the intensive group was 12% lower (95% CI 1-21, p=0.029) for any diabetes-related
      endpoint; 10% lower (-11 to 27, p=0.34) for any diabetes-related death; and 6%
      lower (-10 to 20, p=0.44) for all-cause mortality. Most of the risk reduction in 
      the any diabetes-related aggregate endpoint was due to a 25% risk reduction
      (7-40, p=0.0099) in microvascular endpoints, including the need for retinal
      photocoagulation. There was no difference for any of the three aggregate
      endpoints between the three intensive agents (chlorpropamide, glibenclamide, or
      insulin). Patients in the intensive group had more hypoglycaemic episodes than
      those in the conventional group on both types of analysis (both p<0.0001). The
      rates of major hypoglycaemic episodes per year were 0.7% with conventional
      treatment, 1.0% with chlorpropamide, 1.4% with glibenclamide, and 1.8% with
      insulin. Weight gain was significantly higher in the intensive group (mean 2.9
      kg) than in the conventional group (p<0.001), and patients assigned insulin had a
      greater gain in weight (4.0 kg) than those assigned chlorpropamide (2.6 kg) or
      glibenclamide (1.7 kg). INTERPRETATION: Intensive blood-glucose control by either
      sulphonylureas or insulin substantially decreases the risk of microvascular
      complications, but not macrovascular disease, in patients with type 2
      diabetes.(ABSTRACT TRUNCATED)