Sulfonylurea analogues

Synonyms

Glinides; prandial glucose regulators;

Definition

Glinides belong to the oral antidiabetics, to the group of postprandial glucose regulators (Herold 2020).

The first glinides were approved in Germany in 1999 (repaglinide) and 2001 (nateglinide), respectively (Schatz 2006). In 2005, the prescription reached its peak and has been declining significantly since then. Since July 2016, according to a decision of the G- BA, repaglinide is only reimbursable by the GKV from an eGFR < 25 ml / min, nateglinide not at all (Schwabe 2017).

Glinides are metabolized in the liver and excreted via the bile (Schatz 2006). The half-life is 1 - 1.4 h (Scherbaum 2008).

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)

Guidelines advise against treatment with glinides in the elderly, as there is no evidence of efficacy in reducing the risk of clinical endpoints (Bahrmann 2018).

With regard to long-term use, extensive experience is lacking, as is the safety of combination therapy with metformin (Scherbaum 2008).

1. Bahrmann A et al. (2018) S2k- Guideline Diagnosis, therapy and follow-up of diabetes mellitus in old age. 2nd edition AWMF register number: 057-017
2. Diederich S et al (2020) Reference endocrinology and diabetology. Georg Thieme Verlag Stuttgart 492
3. Freissmuth M et al (2020) Pharmacology and toxicology: from molecular basis to pharmacotherapy. Springer Verlag 687 - 688
4. Herold G et al (2020) Internal medicine. Herold Publishers 734
5. Mehnert H et al (2003) Diabetology in clinic and practice. Georg Thieme Verlag Stuttgart 200
6. Schatz H et al. (2006) Diabetology compact - basics and practice.Thieme Verlag 148 - 156
7. Scherbaum W A et al. (2008) Drug-based antihyperglycemic therapy of diabetes mellitus type 2. Update of the evidence-based guideline of the German Diabetes Society.
8. Schwabe W D et al. (2017) Arzneiverordnungsreport 2017. Springer Verlag 304