Revolutionary Drug for Lowering Cholesterol

Cardiovascular Disease Prevalence and Significance Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the United States and worldwide. In the US alone, a person dies from cardiovascular-related… Continue reading Revolutionary Drug for Lowering Cholesterol

Glucagon receptor antagonist: a diabetes drug development

Glucagon and insulin work in concert to achieve and maintain proper blood glucose levels. Glucagon, released by pancreatic alpha cells, prevents hypoglycemia, while insulin released by beta cells prevents hyperglycemia. Together they preserve a tight blood glucose concentration between 70-100 mg/dL fasting and 70-140 mg/dL after meals. In type 2 diabetes, glucagon production, release, and action are malfunctioning. Overproduction of glucagon leads to over-stimulation of gluconeogenesis and glycolysis, in turn exacerbating hyperglycemia of diabetes mellitus.

It is only natural to look for ways of lowering the synthesis, secretion, or effects of glucagon. In this phase-2 clinical trial, the researchers tested the ability of a glucagon receptor antagonist in lowering A1c in 166 patients with metformin-uncontrolled type 2 diabetes over 12 weeks. The glucagon receptor antagonist RVT-1502, at the high dose 15 mg per day, lowered A1c by 1.0% without severe hypoglycemia. Slight and mild elevation of aminotransferases and blood pressure were documented respectively.

Since study results are meaningfully positive, a follow-up phase-3 randomized clinical trial would be expected.


New drug development for hypercholesterolemia

The study shows that bempedoic acid, when added to statin therapy, reduces LDLc levels further. Bempedoic acid is an inhibitor of ATP citrate lyase, an important enzyme of cholesterol and fatty acid synthesis.

A group of 2300 patients with either established cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) were followed for about 12 months.  Baseline LDLc was 103 mg/dL.  Mean LDLc reduction with bempedoic acid was about 20 mg/dL.

These results are meaningful as it is well-established that the lower the LDLc the lower the ASCVD outcomes.  No increased adverse events were seen with the ATP Citrate lyase inhibitor compared to placebo.