The UKPDS
7 followed 5100 patients with T2DM for 10 years and investigated whether intensive control of glucose would decrease complications. This study
7 also examined whether any of the currently available oral treatments for diabetes were superior. Patients were treated with metformin, sulfonylureas, insulin, or lifestyle changes. The effects of intensive blood pressure control on complications were also assessed. The fasting plasma glucose goal was less than 108 mg/dL, and the blood pressure goal was less than 150/90 mm Hg.
The trial found a significant reduction in combined diabetes-related endpoints, powered primarily by a 25% reduction in microvascular endpoints and by 16% reduction (not statistically significant) in myocardial infarction (
Figure 1) with intensive glucose control.
7 This decrease came from a reduction of HbA
1c levels of only 1% (7.9% vs 7.0%).
7
Further analysis of the relationship between glycemia and risk reduction indicated that each 1% reduction in updated mean HbA
1c was associated with reductions in risk of 21% for any endpoint related to diabetes (95% confidence interval, 17%-24%;
P<.0001), 21% for deaths related to diabetes (15%-27%,
P<.0001), 14% for myocardial infarction (8%-21%,
P<.0001), and 37% for microvascular complications (33%-41%,
P<.0001).
11 No threshold for HbA
1c was observed for risk reduction of any endpoint.
11 This observation led to the speculation that if patients with diabetes had even more aggressive glycemic goals, microvascular and macrovascular complications could be further reduced. Instead of setting HbA
1c goals of 7% to 8%, patients with diabetes could potentially aim for normal HbA
1c levels.
Findings from the UKPDS also indicated that patients treated with metformin had a reduction in diabetes-related endpoints, all-cause mortality, and myocardial infarction.
12 Although the number of obese patients who were treated with metformin was relatively small, the results indicated that metformin may be beneficial for reduction in cardiovascular events.
Data from these studies,
7,11,12 as well as similar data from the smaller Kumamoto study,
13 showed that intensive glucose control in both type 1 and type 2 diabetes mellitus reduced microvascular complications, but more data were needed to answer the question about whether tight glycemic control would significantly reduce cardiovascular events (
Table).
Three major trials—ACCORD, ADVANCE, VADT—have focused on the effect of intensive glucose control on cardiovascular events in patients with T2DM.