UK Prospective Diabetes Study

5,102 newly diagnosed patients with type II diabetes were involved in a prospective, randomised intervention trial.

General conclusions:

• intensive blood glucose control by either sulphonylurea or insulin substantially reduced the risk of microvascular complications, but not macrovascular disease (e.g. stroke, myocardial infarction), in type II diabetics
  
• intensive glucose control with metformin decreased the risk of diabetes related complications in obese type II diabetics; metformin was associated with fewer hypoglycaemic attacks and less weight gain than insulin and sulphonylureas
  
  tight blood pressure control is associated with a lower risk of death and complications related to diabetes; the correlation between blood pressure and cardiovascular disease appears to have no lower threshold - a target blood pressure of 135/85 mmHg or less is appropriate
  
  
• captopril and atenolol were equally effective in reducing diabetic complications
  
  
• target glycosylated haemoglobin concentration should be 7.0% or less

Follow-up after 10 years:

• glycaemic control
  • between-group differences in glycated haemoglobin levels were lost after the first year
  • in the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P=0.04) and microvascular disease (24%, P=0.001), and risk reductions for myocardial infarction (15%, P=0.01) and death from any cause (13%, P=0.007) emerged over time, as more events occurred.
  • in the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P=0.01), myocardial infarction (33%, P=0.005), and death from any cause (27%, P=0.002)
  • despite an early loss of glycaemic differences, a continued reduction in microvascular risk and emergent risk reductions for myocardial infarction and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients (3)
• tight blood pressure control
  • benefits of previously improved blood-pressure control were not sustained when between-group differences in blood pressure were lost. Early improvement in blood-pressure control in patients with both type 2 diabetes and hypertension was associated with a reduced risk of complications, but it appears that good blood-pressure control must be continued if the benefits are to be maintained (4)

Reference:

1. BMJ (1998); 317: 703-26.
2. Lancet (1998); 353: 837-53.
3. Holman RR et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89
4. Holman RR et al. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1565-76