Meglitinide

Glinides are drugs from the group of oral antidiabetic agents that can be used in type 2 diabetes mellitus. In their structure and their mechanism of action they are closely related to the sulfonylureas, and are therefore sometimes known as sulfonylurea analogues. The currently available members of the group are nateglinide and repaglinide.

• 2.1 Therapeutic indications (indications )
• 2.2 contraindications ( contraindications)
• 2.3 Interaction with other drugs
• 2.4 Adverse reactions (side effects)

Pharmacological properties

Pharmacodynamics

As well as the sulfonylureas, glinides act by blocking the ATP - sensitive potassium channels of the β - cells of the pancreas. By this blockage interrupts the resting membrane potential which is maintained by the diffusion of potassium ions substantially together, it comes to membrane depolarization. This leads to opening of voltage-dependent calcium channels and calcium ions flow into the cell. Insulin -containing vesicles fuse with the reinforced membrane ( exocytosis ) leads to an increased release of insulin. Due to this mechanism of action include the glinides to the insulinotropic antidiabetic agents.

Pharmacokinetics

Differences to the sulfonylureas can be found in the pharmacokinetic properties of glinides. Of particular note here are the rapid absorption and short half-life. Thus, nateglinide and repaglinide peak plasma concentrations are reached within about an hour. Among the commonly used sulfonylureas glibenclamide and glimepiride after about two to three hours The short time of Anflutens is also the reason why the intake of glinides should take place just before the main meals. The bioavailability of the glinides is slightly less than that of the sulfonylureas, with 90 to 100% with 60 to 75 %. Metabolism takes place at glinides by the cytochrome P450 enzyme system: nateglinide is va by CYP2C9, repaglinide V.A. mined by CYP2C8. When the elimination glinides show an opposite behavior: The excretion of the metabolites of nateglinide is primarily renal ( via the kidneys ), while metabolites of repaglinide predominantly biliary - ie are excreted - secreted by the bile and ultimately the chair.

Clinical information

Areas of application (indications )

Glinides be used in type 2 diabetes mellitus. According to the practice guideline of the German Diabetes Society does not belong while drugs of first choice, but can be used if sufficient control of metabolism fails in the monotherapy with the biguanide metformin. Repaglinide is approved in addition to the combination with metformin for the monotherapy and nateglinide only for the combination therapy with metformin.

Contraindications ( contraindications)

As insulinotropic antidiabetic agents, the glinides in type 1 diabetes mellitus are contraindicated. In these patients, the β - cells of the pancreas are destroyed by autoimmune reactions, a release of insulin is not possible anymore. Furthermore glinides may not be used in severe liver disease, diabetic ketoacidosis, as well as during pregnancy and lactation. As with all medicines, no use should be made in patients with known hypersensitivity to drugs or adjuvants.

A drug with effects on blood lipid levels - - When repaglinide, the concomitant use with gemfibrozil also is contraindicated. Gemfibrozil is a potent inhibitor of the cytochrome P450 isoenzyme CYP2C8, which is crucially involved in the degradation of repaglinide. Following inhibition of this enzyme by gemfibrozil taking repaglinide plasma levels increase by a multiple, which is accompanied by an uncontrollable increased blood- glucose-lowering effect.

Interactions with other drugs

Due to the mechanism of action and pharmacokinetics of glinides diverse drug-drug interactions may occur. For example, ACE inhibitors increase the blood sugar lowering effect, while diuretics, corticosteroids or sympathomimetics lead to a reduced effect. Analogous inducers - - As shown on the example of the contraindication of simultaneous use of repaglinide and gemfibrozil, and inhibitors of cytochrome P450 enzymes can take a considerable influence on the plasma levels and thus the therapeutic effect of glinides.

Adverse effects (side effects)

Since the release of insulin by insulinotropic antidiabetic agents is independent of the current blood glucose level, consists in application of glinides the risk of hypoglycemic reactions ( low blood sugar ). Due to the short half-life of glinides but especially the nocturnal hypoglycaemia should be lower than the sulfonylureas. Other side effects include at nateglinide often in repaglinide rare gastrointestinal disturbances such as abdominal pain, nausea, vomiting, diarrhea, and equally infrequent in both glinides hypersensitivity reactions ( allergic reactions), elevations of liver enzymes and repaglinide vision problems.

Usefulness of glinides

Glinides should no longer be reimbursed upon request of the G -BA in October 2010 by the SHI, as the benefit has not been established by studies. The Federal Ministry of Health had this request for exclusion Regulation in March 2011 rejected because the inconvenience and inefficiency of glinides could not be detected. The Federal Joint Committee (B -BA ) decided at its meeting on January 23, 2014 to request additional supply relevant studies according to § 92 para 2 SGB V to evaluate the usefulness of glinides ( agents nateglinide, repaglinide ).

Trade names

The following drugs from the group of glinides are currently available for therapy:

• Nateglinide: Starlix ® ( A, D, CH), Starlix ® mite (CH), Trazec ® ( A)
• Repaglinide: repaglinide generic NovoNorm ® ( A, D, CH), Prandin ® ( A)
• Mitiglinid: Glufast ® ( J)