Pharmacodynamics (Effect)
Glinides act in the basement membrane through the sulfonylurea receptor configuration (Schatz 2006). They lead to a short-term insulin secretion from the beta cells by blocking the ATP-sensitive potassium channels (Herold 2020) and thus have a pronounced effect on the postprandial BG glucose (Scherbaum 2008). Fasting BG, on the other hand, is hardly affected (Herold 2020).
Glinides are bound between 90 % and 99 % to plasma proteins (Mehnert 2003).
Indication
The indication for treatment with glinides is a normal-weight (Freissmuth 2020) type 2 diabetic with still existing endogenous insulin production who can only be satisfactorily controlled despite dietary and exercise therapy and with concomitant stage 3 renal insufficiency . Reimbursement by the SHI is now only possible from an eGFR < 25 ml / min (Herold 2020).
Dosage and mode of administration
Prerequisites for treatment with glinides are appropriate training and good compliance of the patient (Herold 2020).
Because of the short half-life of 1 - 1.4 h (Scherbaum 2008), the intake should be immediately before (main) meals (Diederich 2020).
Dosage recommendation: repaglinide 0.5 - 2.0 mg / d. Initially, the lowest dose should be started and then - depending on BG values - the dose should be adjusted accordingly (Herold 2020). The maximum dose is 16 mg / d, the single dose is max. 4 mg (Scherbaum 2008).
In moderate to severe renal insufficiency, the dose may need to be reduced (Schatz 2006).
Repaglinide is approved for combination therapy with metformin (Scherbaum 2008).
Adverse effects
- risk of hypoglycaemia is lower than with sulphonylureas
- gastrointestinal discomfort
- Increase in liver enzymes (rare)
- Allergies
- visual disturbances (Herold 2020)
- sometimes weight gain (Scherbaum 2008)
- cholestatic jaundice (Freissmuth 2020)
Contraindication
- combination with gemfibrozil (Herold 2020)
- combination with other drugs metabolized by CYP2C8
- type 1 diabetes
- acidotic metabolic decompensation
- Precoma
- Coma
- complete secondary failure of treatment with sulfonylureas or their analogues
- severe liver disease
- pancreatectomy
- pregnancy
- breastfeeding
- accidents
- surgical interventions
- inflammations
(Scherbaum 2008)
Interactions
The risk of hypoglycemia is increased with concomitant administration of:
- ACE inhibitors
- Beta-blockers (can mask hypoglycemic symptoms [Freissmuth 2020])
- Glucocorticoids
- Salicylates
- Loop diuretics
- Thiazides
[Freissmuth 2020)
Preparations
In Germany, only repaglinide is approved. As no evidence of efficacy in reducing the risk of clinical endpoints is available to date, the drug is hardly reimbursable under the SHI system (see "Indications" above).
(Herold 2020)