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Glucose lowering drugs provide additional cardiovascular benefit to patients with diabetes.
A type 2 diabetes diagnosis carries with it a two- to threefold increased risk for cardiovascular disease (CVD), including myocardial infarction, stroke, peripheral vascular disease and death from cardiovascular disease. Patients with type 2 diabetes also typically present with several conventional risk factors for CVD including hypertension, lipid disturbances and inflammation.
“That increased risk above individuals who do not have diabetes-men or women who are age-matched-relates, it’s thought, to glucose elevations, but recent clinical trials do not indicate that glucose lowering is the major feature by which protection ensued,” Robert H. Eckel, MD, professor of medicine in the division of endocrinology, metabolism and diabetes, and cardiology at the University of Colorado School of Medicine.
Eckel said historically, trials in type 2 diabetes have compared aggressive treatment with insulin-where the dosage is optimized to lower blood sugar to as close to normal as possible-compared with a group treated close to the standard of care.
“The outcomes of these trials have had pluses and minus,” Eckel said. “There is the suggestion that there might be a benefit for lowering glucose alone but it is not convincing enough to say that it is the only important risk factor for heart disease in patients with diabetes. “
Next: New drug classes
In recent years, two new classes of drugs have shown benefit in reducing CVD events in patients with type 2 diabetes.
The first, sodium-glucose cotransporter-2 (SGLT2) inhibitors, lower blood glucose by causing the kidneys to excrete sugar from the body through the urine.
“Typically patients with diabetes can excrete glucose in their urine when glucose levels are above 200 mg/dL,” Eckel explained. “These drugs prevent the high glucose from occurring because they allow glucose to be excreted in urine when levels are still within the normal range.”
According to Eckel, two drugs within this class have shown benefit on CVD outcomes.
For example, results of the EASEL study, published recently in Circulation, showed that among patients with type 2 diabetes with established CVD, initiation on an SGLT2 inhibitor was associated with a lower rate of all-cause mortality, hospitalization for heart failure and major cardiovascular endpoints, compared with non-initiation.
A second class of injectable drugs-glucagon-like peptide-1 (GLP-1) receptor antagonists-has also been shown to reduce the risk for CVD outcomes.
“This is another class of drugs that is glucose lowering, but the amount of glucose lowering has not explained the entire benefit,” Eckel said.
Now physicians are able to pick a drug that can reduce patients risk for CVD events beyond just lowering blood glucose, Eckel said. However, he pointed out that these new classes of drugs are expensive and access may be limited for people with no or inadequate insurance coverage.
“I must admit as person who takes care of patients with diabetes that after a patient is treated with metformin, one of these agents should take second place to lower their glucose,” Eckel said. “That is particularly relevant because of the reduction in CVD events to follow.”