Coronary events decreased significantly with intensive glycemic control in type 2 diabetes

Issue: June 2009

Intensive glycemic control compared with standard glycemic control significantly reduced coronary events in a large cohort of patients with type 2 diabetes. However, there was no clear benefit on all-cause mortality.

In a meta-analysis of five randomized, controlled trials (UKPDS, PROactive, ADVANCE, VADT and ACCORD) including 33,040 patients, researchers examined the effect of an intensive glucose-lowering regimen on death and cardiovascular outcomes in comparison with a standard regimen.

The researchers gathered data that occurred during about 163,000 person-years of follow-up on nonfatal myocardial infarction events (n=1,497), coronary heart disease (n=2,318), stroke (n=1,127) and all-cause mortality (n=2,892). The researchers conducted a random-effects meta-analysis to obtain summary effect estimates for clinical outcomes with the use of ORs calculated from raw data from all five trials.

Patients in the intensive glucose-lowering treatment group had a significant reduction in nonfatal MI events by 17% and CHD events by 15%. Intensive treatment did not significantly affect stroke or all-cause mortality. When compared with standard treatment, intensive glucose-lowering treatment significantly reduced nonfatal MI and CHD events.

In addition, severe hypoglycemia was significantly less common compared with hypoglycemia. However, a severe hypoglycemia event occurred in 2.3% of patients assigned to intensive treatment compared with 1.2% of patients assigned to standard treatment.

Patients assigned to intensive treatment had a lower mean HbA1c concentration of 0.9% compared with patients assigned to standard treatment.

Although 2.3 fewer MI events or 2.9 fewer CHD events took place for each 200 patients assigned to intensive glucose-lowering treatment for five years, event rates for stroke and all-cause mortality were not significantly different between treatment groups.

“The benefit of glucose control on CHD in type 2 diabetes will certainly not be as great as that produced by blood pressure control or statin treatment,” Theodore Mazzone, MD, professor of medicine and pharmacology and chief in the section of endocrinology, diabetes and metabolism at the University of Illinois at Chicago, wrote in an accompanying editorial. “However, on the basis of current information and the urgent need to address residual risk of CHD in a rapidly expanding population with type 2 diabetes, it is premature to conclude that glucose control has no part to play.” – by Jennifer Southall

Ray KR. Lancet. 2009;373:1765-1772.

In this meta-analysis there were no new findings, but what is important is that it drove the point home that early and aggressive control of diabetes is essential. It also showed that an effect can be made on CV events and nonfatal MI — there was a significant reduction in nonfatal MI if one adds up all the patients from the included studies. The remaining question in the field of diabetes has been: what about the effect of glucose control on macrovascular complications? The researchers of these studies tried to answer this and the implication is that we should not hesitate to try and control diabetes, and hopefully the patients will also reap the benefit as far as the CV complications go in addition to the benefit on microvascular complications. The issue is that physicians have usually waited too long to institute intensive glucose control. In most of the studies included in the meta-analysis the researchers are looking at patients with type 2 diabetes who are at very high CV risk because they have had diabetes for a long time and have been poorly controlled. So, in a way, these studies have not been done in the right sample of patients. Almost everyone is coming to the conclusion that you have to get to patients before they have established CV disease to prevent these complications. The real problem, albeit a good one, has been that the overall rate of CV events is so much smaller now than in the past that it becomes very difficult to design a study that lasts long enough and includes enough patients to have enough events to ultimately show an effect of any treatment on primary cardiovascular endpoints. I do not think general public understands what advances we have made over the past two decades in controlling other cardiac rsisks, in particular high BP and high cholesterol.
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– George Grunberger, MD

Chairman of Grunberger Diabetes Institute,
Professor of Internal Medicine, Wayne State University School of Medicine, Detroit