Bromocriptine-QR slashes cardiovascular events in diabetics on metformin

DALLAS – The quick-release formulation of bromocriptine known as Cycloset shows strong potential as a novel approach for cardiovascular risk reduction in type 2 diabetic patients already on metformin, according to Dr. Bindu Chamarthi.

A post-hoc analysis of 1,791 such patients who participated in the 1-year double-blind Cycloset Safety Trial showed a 53% reduction in cardiovascular events in those randomized to bromocriptine-QR, compared with placebo-treated controls, Dr. Chamarthi reported at the American Heart Association scientific sessions.

The composite cardiovascular endpoint comprising a first MI, stroke, coronary revascularization, or hospitalization for either angina or heart failure occurred in 1.3% of 1,208 bromocriptine-QR–treated patients, compared with 3.1% of 583 placebo-treated controls. All subjects were on metformin at baseline, were generally in good metabolic control, and had high rates of utilization of guideline-recommended cardioprotective medications, including statins and antihypertensive agents, noted Dr. Chamarthi, an endocrinologist at Brigham and Women’s Hospital, Boston.

This sharp reduction in cardiovascular events is particularly impressive in light of the increased risk of such events faced by patients with type 2 diabetes, along with the lack of conclusive evidence of cardiovascular benefit for any of the approved therapies for the disease other than metformin, she added.

Bromocriptine-QR is approved by the Food and Drug Administration for the treatment of type 2 diabetes, so it’s not surprising that the group assigned to the drug evidenced improved glycemic control. At the end of 52 weeks of treatment, they were 1.75-fold more likely than controls to be in good glycemic control, as defined by a hemoglobin A_1c level of 7.0% or less.

Current evidence suggests that the development of obesity, insulin resistance, and diabetes is linked to a central hypodopaminergic state.

Bromocriptine-QR is a sympatholytic dopamine agonist approved in 2009. Taken once daily with breakfast, it provides a circadian-timed brief period of increased central dopaminergic activity. The result is improved postprandial blood glucose control without raising the insulin concentration.

How bromocriptine-QR achieved the observed reduction in cardiovascular events seen in this study remains unclear. One possibility is that the mechanism involves a reduction in elevated sympathetic nervous system drive to the vasculature, liver, and adipose tissue along with a reduction in hypothalamic-pituitary-adrenal axis activity, with resultant diminution of endothelial dysfunction. These benefits might flow from the drug’s ability to restore the daily morning peak in central circadian dopaminergic neuroendocrine activities that are disrupted in patients with type 2 diabetes. Further studies are planned, according to Dr. Chamarthi.

This study was sponsored by VeroScience, which markets bromocriptine-QR. Dr. Chamarthi is a consultant for the company.

bjancin@frontlinemedcom.com

DALLAS – The quick-release formulation of bromocriptine known as Cycloset shows strong potential as a novel approach for cardiovascular risk reduction in type 2 diabetic patients already on metformin, according to Dr. Bindu Chamarthi.

A post-hoc analysis of 1,791 such patients who participated in the 1-year double-blind Cycloset Safety Trial showed a 53% reduction in cardiovascular events in those randomized to bromocriptine-QR, compared with placebo-treated controls, Dr. Chamarthi reported at the American Heart Association scientific sessions.

The composite cardiovascular endpoint comprising a first MI, stroke, coronary revascularization, or hospitalization for either angina or heart failure occurred in 1.3% of 1,208 bromocriptine-QR–treated patients, compared with 3.1% of 583 placebo-treated controls. All subjects were on metformin at baseline, were generally in good metabolic control, and had high rates of utilization of guideline-recommended cardioprotective medications, including statins and antihypertensive agents, noted Dr. Chamarthi, an endocrinologist at Brigham and Women’s Hospital, Boston.

This sharp reduction in cardiovascular events is particularly impressive in light of the increased risk of such events faced by patients with type 2 diabetes, along with the lack of conclusive evidence of cardiovascular benefit for any of the approved therapies for the disease other than metformin, she added.

Bromocriptine-QR is approved by the Food and Drug Administration for the treatment of type 2 diabetes, so it’s not surprising that the group assigned to the drug evidenced improved glycemic control. At the end of 52 weeks of treatment, they were 1.75-fold more likely than controls to be in good glycemic control, as defined by a hemoglobin A_1c level of 7.0% or less.

Current evidence suggests that the development of obesity, insulin resistance, and diabetes is linked to a central hypodopaminergic state.

Bromocriptine-QR is a sympatholytic dopamine agonist approved in 2009. Taken once daily with breakfast, it provides a circadian-timed brief period of increased central dopaminergic activity. The result is improved postprandial blood glucose control without raising the insulin concentration.

How bromocriptine-QR achieved the observed reduction in cardiovascular events seen in this study remains unclear. One possibility is that the mechanism involves a reduction in elevated sympathetic nervous system drive to the vasculature, liver, and adipose tissue along with a reduction in hypothalamic-pituitary-adrenal axis activity, with resultant diminution of endothelial dysfunction. These benefits might flow from the drug’s ability to restore the daily morning peak in central circadian dopaminergic neuroendocrine activities that are disrupted in patients with type 2 diabetes. Further studies are planned, according to Dr. Chamarthi.

This study was sponsored by VeroScience, which markets bromocriptine-QR. Dr. Chamarthi is a consultant for the company.

bjancin@frontlinemedcom.com

DALLAS – The quick-release formulation of bromocriptine known as Cycloset shows strong potential as a novel approach for cardiovascular risk reduction in type 2 diabetic patients already on metformin, according to Dr. Bindu Chamarthi.

A post-hoc analysis of 1,791 such patients who participated in the 1-year double-blind Cycloset Safety Trial showed a 53% reduction in cardiovascular events in those randomized to bromocriptine-QR, compared with placebo-treated controls, Dr. Chamarthi reported at the American Heart Association scientific sessions.

The composite cardiovascular endpoint comprising a first MI, stroke, coronary revascularization, or hospitalization for either angina or heart failure occurred in 1.3% of 1,208 bromocriptine-QR–treated patients, compared with 3.1% of 583 placebo-treated controls. All subjects were on metformin at baseline, were generally in good metabolic control, and had high rates of utilization of guideline-recommended cardioprotective medications, including statins and antihypertensive agents, noted Dr. Chamarthi, an endocrinologist at Brigham and Women’s Hospital, Boston.

This sharp reduction in cardiovascular events is particularly impressive in light of the increased risk of such events faced by patients with type 2 diabetes, along with the lack of conclusive evidence of cardiovascular benefit for any of the approved therapies for the disease other than metformin, she added.

Bromocriptine-QR is approved by the Food and Drug Administration for the treatment of type 2 diabetes, so it’s not surprising that the group assigned to the drug evidenced improved glycemic control. At the end of 52 weeks of treatment, they were 1.75-fold more likely than controls to be in good glycemic control, as defined by a hemoglobin A_1c level of 7.0% or less.

Current evidence suggests that the development of obesity, insulin resistance, and diabetes is linked to a central hypodopaminergic state.

Bromocriptine-QR is a sympatholytic dopamine agonist approved in 2009. Taken once daily with breakfast, it provides a circadian-timed brief period of increased central dopaminergic activity. The result is improved postprandial blood glucose control without raising the insulin concentration.

How bromocriptine-QR achieved the observed reduction in cardiovascular events seen in this study remains unclear. One possibility is that the mechanism involves a reduction in elevated sympathetic nervous system drive to the vasculature, liver, and adipose tissue along with a reduction in hypothalamic-pituitary-adrenal axis activity, with resultant diminution of endothelial dysfunction. These benefits might flow from the drug’s ability to restore the daily morning peak in central circadian dopaminergic neuroendocrine activities that are disrupted in patients with type 2 diabetes. Further studies are planned, according to Dr. Chamarthi.

This study was sponsored by VeroScience, which markets bromocriptine-QR. Dr. Chamarthi is a consultant for the company.

bjancin@frontlinemedcom.com