Nicotinic acid

Table of contents

• What is nicotinic acid?
• How does nicotinic acid work?
• Which conditions is it used or studied for?
• How is nicotinic acid given?
• What do the clinical trials show?
• What side effects are known?

What is nicotinic acid?

Nicotinic acid, also called niacin or vitamin B3, is a water-soluble vitamin of the B complex. It is a chemically synthesised small molecule with the formula C6H5NO2.^[3] It is already an authorised medicine: an extended-release tablet form was first approved in the United States in 1997, and it is marketed under trade names including Niaspan, Niacor, and Nicolar.^[2][3] Other names for the same substance include 3-pyridinecarboxylic acid and pyridine-3-carboxylic acid.^[3] In the clinical trial described on this page, nicotinic acid is being tested in a new formulation called controlled-ileal-release nicotinic acid (CIR-NA).

How does nicotinic acid work?

Nicotinic acid is a vitamin that the body uses for many metabolic processes. As a medicine, it is known to change blood fat levels: it reduces elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B) and triglycerides (TG), while increasing high-density lipoprotein cholesterol (HDL-C).^[2] The new controlled-ileal-release formulation is designed to release the substance in a specific part of the small intestine, the ileum. The trial aims to find out whether this targeted release can induce remission of prediabetes, but the exact mechanism by which CIR-NA might affect blood sugar is not described in the available registry data.^[1]

Which conditions is it used or studied for?

Nicotinic acid is authorised for use in several lipid disorders, and it is now being studied in prediabetes:

• Primary hyperlipidemia and mixed dyslipidemia — conditions where blood levels of cholesterol and triglycerides are too high; nicotinic acid is authorised to reduce these levels.^[2]
• Reducing the risk of recurrent nonfatal myocardial infarction — in people who have already had a heart attack and have hyperlipidemia.^[2]
• Atherosclerotic disease — in combination with a bile acid binding resin, nicotinic acid can slow progression or promote regression of atherosclerotic disease in people with a history of coronary artery disease and hyperlipidemia.^[2]
• Severe hypertriglyceridemia — very high triglyceride levels in adults.^[2]
• Prediabetes — a condition where blood sugar is higher than normal but not yet high enough for a diagnosis of type 2 diabetes; this is the condition being investigated in the current Phase 2 trial.^[1]

How is nicotinic acid given?

The authorised medicine comes as an extended-release tablet for oral use, taken once daily at a dose between 500 mg and 2000 mg.^[2] The investigational formulation in the clinical trial is also given by mouth, as a 200 mg oral dose of controlled-ileal-release nicotinic acid.^[1] The trial also includes a placebo arm, which is an inactive substance used for comparison.

What do the clinical trials show?

One clinical trial of nicotinic acid in prediabetes is currently listed in the registry. It is a Phase 2 interventional study that has been authorised and plans to enrol 390 participants.^[1] The trial compares oral controlled-ileal-release nicotinic acid at a dose of 200 mg against a placebo. The main outcome being measured is remission of prediabetes at week 26, meaning whether participants no longer meet the criteria for prediabetes after 26 weeks of treatment.^[1] Because the trial is still in the authorised stage, no results are available yet.

What side effects are known?

The available sources do not provide a specific list of side effects for the controlled-ileal-release formulation being studied. The prescribing information for the authorised extended-release niacin tablet describes flushing as a well-known effect of nicotinic acid, and it includes warnings about liver effects, muscle effects, and increased blood sugar, but detailed side effect frequencies are not included in the provided data.^[2] Because the trial formulation is different from the authorised tablet, the side effect profile in prediabetes may not be the same. No side effect data from the prediabetes trial are available at this stage.^[1]