Products
Repaglinide is commercially available in tablet form (NovoNorm, generic). It was approved in many countries in 1999.
Structure and properties
Repaglinide (C27H36N2O4, Mr = 452.6 g/mol) is a meglitinide and carbamoylmethylbenzoic acid derivative without sulfonylurea structure. It is a white, odorless powder that is practically insoluble in water due to its lipophilicity. In drugs, it is present as -enantiomer, which is significantly more potent than the -enantiomer.
Effects
Repaglinide (ATC A10BX02) has antidiabetic, insulin secretagogue, and blood glucose-lowering properties. The mechanism of action is essentially identical to that of sulfonylureas. Repaglinide also closes ATP-dependent potassium channels, ultimately increasing insulin secretion from the beta cell. Unlike the sulfonylureas, it binds to a different binding site. Repaglinide is short-acting (half-life approximately 1 hour) and is particularly effective against postprandial hyperglycemia, i.e., elevated blood glucose levels after meals. It can reduce the risk of hypoglycemia between meals or at night.
Indications
For the treatment of type 2 diabetes mellitus. Repaglinide may be combined with metformin, a glitazone, or insulins.
Dosage
According to the SmPC. Repaglinide is taken before a main meal. The meal should be eaten within 30 minutes. The usual single dose is 0.5 mg, up to a maximum of 4 mg. The maximum daily dose is 12 mg.
Contraindications
- Hypersensitivity
- Diabetes mellitus type 1
- Diabetic ketoacidosis
- Pregnancy and lactation
- Children and adolescents under 18 years
- Severe liver dysfunction
- Concurrent use of gemfibrozil
For complete precautions, see the drug label.
Interactions
Repaglinide is biotransformed to inactive metabolites by CYP3A4 and CYP2C8. Interactions are possible with inducers and inhibitors of these isoenzymes. Gemfibrozil is a potent inhibitor of CYP2C8 and can greatly increase bioavailability and plasma levels. Therefore, concomitant use is contraindicated. Full drug-drug interaction information can be found in the Drug Information Leaflet.
Adverse effects
The most common adverse effect is hypoglycemia, which occurs primarily in combination with other antidiabetic agents. In contrast, it is considered rare in monotherapy. Rarely, gastrointestinal disturbances and allergic reactions may occur. Very rare are liver dysfunction, elevated liver enzymes, and visual disturbances due to fluctuating blood glucose levels. The literature further mentions upper respiratory tract infections as a possible adverse effect.
