Achieve tight glycemic control to reduce macrovascular events and achieve microvascular benefits.

Patients with diabetes are at increased risk for adverse cardiovascular events, with rates of MI similar to that of patients with known IHD. Microvascular complications, such as retinopathy and nephropathy, are decreased with improving glycemic control. There is conflicting evidence on whether tight glycemic control reduces macrovascular events, such as MI and stroke. Tight control of glucose in both type 1 and type 2 diabetes is recommended because of potential reduction of macrovascular events and proven microvascular benefits.

Tight glycemic control has been associated with decline in microvascular complications in the Diabetes Control and Complications Trial (DCCT, 1995) for type 1 diabetes, and in the United Kingdom Prospective Diabetes Study (UKPDS, 1998) for type 2 diabetes. Reduction of macrovascular events has not been conclusively demonstrated in RCTs comparing tight glycemic control with conventional treatment. DCCT was not powered to demonstrate a decrease in coronary events, although there was a trend towards benefits.

A two-year VA Cooperative feasibility trial of intense treatment of type 2 diabetics (VA CSDM, 1997) found no difference in cardiovascular events, compared with a standard treatment group. Similarly, a Japanese study found no benefit of tight glycemic control for macrovascular disease.

The recent UKPDS study, lasting nearly 10 years, evaluated treatment outcomes in newly-diagnosed type 2 diabetics. Using different pharmacological agents (e.g., insulin, metformin, and several sulfonylureas), several intensive treatment strategies were compared to usual care. The intensive treatment group included those treated initially with insulin, a sulfonylurea, or metformin; other drugs were added to these regimens to maintain glycemic control over time.

There was a non-significant trend toward improved cardiovascular outcomes (p<0.052). The results were significant in the intensively treated insulin and sulfonylurea groups, compared to conventional groups. (16% relative risk reduction, 2.7% absolute risk reduction; NNT=37 for patients treated for 10 years). In the metformin intensively treated group, there was a significant (p=0.01) 39% relative risk reduction in MI (absolute risk reduction, 7% over 10 years; NNT=14 patients treated for 10 years to avoid one MI).

Thus, there does not seem to be any harm, and may be a benefit in cardiovascular outcomes with intensive treatment of type II diabetes. Because of microvascular benefits of intensive glycemic control, the VHA/DoD Clinical Guideline for the Management of Patients with Diabetes Mellitus recommends treating diabetics with tight control, if life expectancy is such that they will possibly benefit from these measures.