Combination Therapy Can Help Dyslipidemia in Diabetes

While hyperglycemia is a risk factor for microvascular complications, most patients die of macrovascular disease, which is strongly influenced by dyslipidemia.

Treatment of type 2 diabetes must address both hyperglycemia and atherogenic dyslipidemia, according to information presented by an expert panel during “Multifactorial Risk Reduction for Patients with Type 2 Diabetes: Consideration for the Cardiometabolic Effects of Treatment Choices,” a satellite symposium at the 19th Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinologists. While hyperglycemia is the major risk factor for microvascular complications, most patients die of macrovascular disease, which is strongly influenced by dyslipidemia, they said.

“Multiple interventions may be required,” said Pasquale Palumbo, MD, Professor of Medicine at the Mayo Clinic in Scottsdale, Arizona. An individual’s “metabolic risk” for both diabetes and cardiovascular disease is increased by elevated LDL cholesterol, lower HDL cholesterol, elevated triglycerides, elevated plasma glucose, hypertension, and an enlarged waist circumference, among other factors, he said. “The reason for early intervention in patients with impaired glucose tolerance is the risk for cardiovascular health.”

While 7% or less is the usual upper target limit for A1C (glycosylated hemoglobin), there is no single correct value for all patients. “Clinical judgment is needed,” he said. More importantly, he noted, “We still have not achieved our goals” for correcting A1C levels in the large majority of patients, and only 7% of adults with diabetes have achieved reduction in three major risk factors: A1C less than 7%, blood pressure less than 130/80 mm Hg, and total cholesterol less than 200 mg/dL.

Obesity and dyslipidemia are central to the problem of diabetes in both men and women, he said.

Microalbuminuria is “a powerful predictor of cardiovascular disease outcomes,” according to Matthew Weir, MD, Professor of Nephrology, University of Maryland School of Medicine in Baltimore. Protein in the urine may reflect generalized endothelial dysfunction, hemostasis abnormalities, and greater severity of end organ damage.

There is evidence that treatment of patients with high protein using renin-angiotensin system blockers can cut risk of death. “But we’d like to move to a world of primary prevention,” he said. However, a recent trial testing whether reducing activity of the renin-angiotensin system could delay nephropathy in diabetes showed no benefit for blockade of the system. “Current evidence does not support blockade for primary renal protection in normalbuminuric, normotensive diabetic patients,” he said.

Combination therapy is a valuable strategy for diabetes patients with dyslipidemia, according to Phillip Levy, MD, Clinical Professor of Medicine at the University of Arizona at Phoenix. In addition, he said, “Diet is crucial,” because weight loss can reduce hyperglycemia, dyslipidemia, and hypertension.

The American Association of Clinical Endocrinologists offers an algorithm for intervention based on A1C levels, available at the AACE website.

There is a wide range of drug classes currently available for treatment, which can be used in combination based on complementary mechanisms of action. For control of dyslipidemia, there are six classes of agents: statins, fibrates, niacin, cholesterol absorption inhibitors, omega-3 fatty acids, and bile acid sequestrants. The choice of agent depends on the precise abnormality being targeted.

If the goal is to lower LDLs, statins are the first choice, followed by bile acid sequestration, cholesterol absorption inhibitors, or fibrates. Two of these can be combined.

When bile acids are sequestered in the gastrointestinal tract, they cannot be reabsorbed, Levy explained. This causes the liver to synthesize more bile acids, using cholesterol, thus lowering cholesterol in the blood. Sequestrants also reduce blood glucose, through mechanisms that are not entirely clear.

When statins and sequestrants are used together, LDL can be reduced by up to 70%, although there are limitations due to drug interactions. Each of the other possible combinations with statins also carries some limitations.

This satellite symposium was sponsored by Daiichi-Sankyo, Inc. and presented at the 19th Annual Meeting and Clinical Congress of the American Association of Clinical Endocrinologists