Intensive Glucose Control Fails to Cut CV Risks, Mortality

Intensive glucose control isn't any more effective than standard therapy at reducing the rates of major cardiovascular events, death, or microvascular disease in patients with poorly controlled type 2 diabetes, a prospective study of nearly 1,800 such patients has indicated.

In fact, patients assigned to intensive therapy were significantly more likely to experience hypoglycemia, dyspnea, and other serious adverse events, the investigators wrote.

Given these findings, the authors recommended that preventive efforts focus on factors more directly tied to cardiovascular health. “For now, appropriate management of hypertension, dyslipidemia, and other cardiovascular risk factors appears to be the most effective approach to preventing cardiovascular morbidity and mortality” in these patients, wrote Dr. William Duckworth of the Phoenix Veterans Affairs Health Care Center and his colleagues (N. Engl. J. Med. 2008 Dec. 17 [doi:10.1056/NEJMoa0808431]).

The Veterans Affairs Diabetes Trial (VADT) examined the effect of intensive glucose control in 1,791 military veterans (mean age, 60 years) who had poorly controlled type 2 diabetes. Patients were randomized to either standard or intensive glucose control therapy. In both groups, obese patients (those with a body mass index of 27 kg/m

The primary outcome was the time from randomization to a first major cardiovascular event, heart failure, surgery for vascular disease, or amputation for ischemic gangrene.

At 3 months, median HbA1c had decreased in both groups; by 6 months, it had stabilized at 8% in the standard therapy group and 7% in the intensive therapy group.

After a median follow-up of 6 years, the investigators found that those in the intensive therapy group were 12% less likely than those in the standard care group to have had a cardiovascular event (not a significant difference). Nor were there significant differences in any of the individual cardiovascular end points, or in the rate of cardiovascular deaths.

Intensive therapy did not significantly affect any of the outcomes associated with microvascular disease. There were no significant between-group differences in amputation. And although the investigators found a slight reduction in diabetic retinopathy in the intensive therapy group, it was nonsignificant. Intensive therapy did not significantly improve renal function or slow its decline, and was associated with a nonsignificant increase in autonomic neuropathy.

Patients in the intensive therapy group had significantly more adverse events than did those in the standard therapy group. The most common was hypoglycemia (1,566 vs. 432 incidents per 100 patient-years). Significantly more patients in the intensive therapy group had at least one serious adverse event (24% vs. 18%). Among these, dyspnea was the most commonly reported.

There were 95 deaths from any cause in the standard therapy group, and 102 in the intensive therapy group, which was not a significant difference.

The results of VADT agree with those of two other large trials—ACCORD (Action to Control Cardiovascular Risk in Diabetes) and ADVANCE (Action in Diabetes and Vascular Disease)—that examined the effect of intensive glucose control, the authors said. “Intensive glucose control did not reduce cardiovascular events [in these trials]. The ACCORD study was terminated at 3.5 years because of increased mortality in the intensive therapy group. The ADVANCE study showed a reduction in the progression of albuminuria, but there were no changes in the rates of severe nephropathy, retinopathy, or cardiovascular events.”

The American Association of Clinical Endocrinologists (AACE) presented its view of the VADT results on the AACE Web site (www.aace.com

The committee emphasized that “AACE… continue[s] to advocate good glycemic control for diabetic patients, recognizing that treatment targets and strategies have to be individualized.”

The study was sponsored by the Department of Veterans Affairs, the American Diabetes Association, and the National Eye Institute, with additional funding from various pharmaceutical companies. Dr. Duckworth and his coauthors reported numerous financial connections with those companies.

'Appropriate management of … risk factors appears to be the most effective approach.' DR. DUCKWORTH

Intensive glucose control isn't any more effective than standard therapy at reducing the rates of major cardiovascular events, death, or microvascular disease in patients with poorly controlled type 2 diabetes, a prospective study of nearly 1,800 such patients has indicated.

In fact, patients assigned to intensive therapy were significantly more likely to experience hypoglycemia, dyspnea, and other serious adverse events, the investigators wrote.

Given these findings, the authors recommended that preventive efforts focus on factors more directly tied to cardiovascular health. “For now, appropriate management of hypertension, dyslipidemia, and other cardiovascular risk factors appears to be the most effective approach to preventing cardiovascular morbidity and mortality” in these patients, wrote Dr. William Duckworth of the Phoenix Veterans Affairs Health Care Center and his colleagues (N. Engl. J. Med. 2008 Dec. 17 [doi:10.1056/NEJMoa0808431]).

The Veterans Affairs Diabetes Trial (VADT) examined the effect of intensive glucose control in 1,791 military veterans (mean age, 60 years) who had poorly controlled type 2 diabetes. Patients were randomized to either standard or intensive glucose control therapy. In both groups, obese patients (those with a body mass index of 27 kg/m

The primary outcome was the time from randomization to a first major cardiovascular event, heart failure, surgery for vascular disease, or amputation for ischemic gangrene.

At 3 months, median HbA1c had decreased in both groups; by 6 months, it had stabilized at 8% in the standard therapy group and 7% in the intensive therapy group.

After a median follow-up of 6 years, the investigators found that those in the intensive therapy group were 12% less likely than those in the standard care group to have had a cardiovascular event (not a significant difference). Nor were there significant differences in any of the individual cardiovascular end points, or in the rate of cardiovascular deaths.

Intensive therapy did not significantly affect any of the outcomes associated with microvascular disease. There were no significant between-group differences in amputation. And although the investigators found a slight reduction in diabetic retinopathy in the intensive therapy group, it was nonsignificant. Intensive therapy did not significantly improve renal function or slow its decline, and was associated with a nonsignificant increase in autonomic neuropathy.

Patients in the intensive therapy group had significantly more adverse events than did those in the standard therapy group. The most common was hypoglycemia (1,566 vs. 432 incidents per 100 patient-years). Significantly more patients in the intensive therapy group had at least one serious adverse event (24% vs. 18%). Among these, dyspnea was the most commonly reported.

There were 95 deaths from any cause in the standard therapy group, and 102 in the intensive therapy group, which was not a significant difference.

The results of VADT agree with those of two other large trials—ACCORD (Action to Control Cardiovascular Risk in Diabetes) and ADVANCE (Action in Diabetes and Vascular Disease)—that examined the effect of intensive glucose control, the authors said. “Intensive glucose control did not reduce cardiovascular events [in these trials]. The ACCORD study was terminated at 3.5 years because of increased mortality in the intensive therapy group. The ADVANCE study showed a reduction in the progression of albuminuria, but there were no changes in the rates of severe nephropathy, retinopathy, or cardiovascular events.”

The American Association of Clinical Endocrinologists (AACE) presented its view of the VADT results on the AACE Web site (www.aace.com

The committee emphasized that “AACE… continue[s] to advocate good glycemic control for diabetic patients, recognizing that treatment targets and strategies have to be individualized.”

The study was sponsored by the Department of Veterans Affairs, the American Diabetes Association, and the National Eye Institute, with additional funding from various pharmaceutical companies. Dr. Duckworth and his coauthors reported numerous financial connections with those companies.

'Appropriate management of … risk factors appears to be the most effective approach.' DR. DUCKWORTH

Intensive glucose control isn't any more effective than standard therapy at reducing the rates of major cardiovascular events, death, or microvascular disease in patients with poorly controlled type 2 diabetes, a prospective study of nearly 1,800 such patients has indicated.

In fact, patients assigned to intensive therapy were significantly more likely to experience hypoglycemia, dyspnea, and other serious adverse events, the investigators wrote.

Given these findings, the authors recommended that preventive efforts focus on factors more directly tied to cardiovascular health. “For now, appropriate management of hypertension, dyslipidemia, and other cardiovascular risk factors appears to be the most effective approach to preventing cardiovascular morbidity and mortality” in these patients, wrote Dr. William Duckworth of the Phoenix Veterans Affairs Health Care Center and his colleagues (N. Engl. J. Med. 2008 Dec. 17 [doi:10.1056/NEJMoa0808431]).

The Veterans Affairs Diabetes Trial (VADT) examined the effect of intensive glucose control in 1,791 military veterans (mean age, 60 years) who had poorly controlled type 2 diabetes. Patients were randomized to either standard or intensive glucose control therapy. In both groups, obese patients (those with a body mass index of 27 kg/m

The primary outcome was the time from randomization to a first major cardiovascular event, heart failure, surgery for vascular disease, or amputation for ischemic gangrene.

At 3 months, median HbA1c had decreased in both groups; by 6 months, it had stabilized at 8% in the standard therapy group and 7% in the intensive therapy group.

After a median follow-up of 6 years, the investigators found that those in the intensive therapy group were 12% less likely than those in the standard care group to have had a cardiovascular event (not a significant difference). Nor were there significant differences in any of the individual cardiovascular end points, or in the rate of cardiovascular deaths.

Intensive therapy did not significantly affect any of the outcomes associated with microvascular disease. There were no significant between-group differences in amputation. And although the investigators found a slight reduction in diabetic retinopathy in the intensive therapy group, it was nonsignificant. Intensive therapy did not significantly improve renal function or slow its decline, and was associated with a nonsignificant increase in autonomic neuropathy.

Patients in the intensive therapy group had significantly more adverse events than did those in the standard therapy group. The most common was hypoglycemia (1,566 vs. 432 incidents per 100 patient-years). Significantly more patients in the intensive therapy group had at least one serious adverse event (24% vs. 18%). Among these, dyspnea was the most commonly reported.

There were 95 deaths from any cause in the standard therapy group, and 102 in the intensive therapy group, which was not a significant difference.

The results of VADT agree with those of two other large trials—ACCORD (Action to Control Cardiovascular Risk in Diabetes) and ADVANCE (Action in Diabetes and Vascular Disease)—that examined the effect of intensive glucose control, the authors said. “Intensive glucose control did not reduce cardiovascular events [in these trials]. The ACCORD study was terminated at 3.5 years because of increased mortality in the intensive therapy group. The ADVANCE study showed a reduction in the progression of albuminuria, but there were no changes in the rates of severe nephropathy, retinopathy, or cardiovascular events.”

The American Association of Clinical Endocrinologists (AACE) presented its view of the VADT results on the AACE Web site (www.aace.com

The committee emphasized that “AACE… continue[s] to advocate good glycemic control for diabetic patients, recognizing that treatment targets and strategies have to be individualized.”

The study was sponsored by the Department of Veterans Affairs, the American Diabetes Association, and the National Eye Institute, with additional funding from various pharmaceutical companies. Dr. Duckworth and his coauthors reported numerous financial connections with those companies.

'Appropriate management of … risk factors appears to be the most effective approach.' DR. DUCKWORTH