Glitazones

Assignment: Glitazones belong to the group of oral antidiabetics. In the USA, pioglitazone was approved as the 1st representative of this group of substances in 1997 (Schwabe 2013). In 2000, two more drugs came on the market (Erdmann 2004):troglitazone and rosiglitazone. Because several cases of fulminant liver failure occurred during therapy with troglitazone, the substance was withdrawn from the market again in the USA in March 2005 (Matthaei (2001).

One year after its introduction, rosiglitazone was already among the 2,500 most frequently prescribed drugs. However, the therapy costs are very high (Schwabe 2013).

In Germany, only pioglitazone is currently approved (Diederich 2020), as rosiglitazone was also withdrawn from the market in November 2010 due to an increase in cardiovascular adverse events (Biermann 2010 / Kleinhans 2005).

Effect:

• Reduction of insulin resistance by binding to the nuclear receptor PPAR- gamma, which is most abundant in adipocytes.
• Promotion of the redistribution of fat (visceral fat to peripheral sites)
• lowers insulin levels
• Pioglitazone:
  • increases HDL more than LDL
  • lowers triglycerides

(Kasper 2015)

• both the fasting BG value and the HbA1c decrease
• BG uptake in the muscle is significantly increased
• patients with microalbuminuria showed a significant decrease in albumin excretion in two studies
• the progression of diabetic nephropathy is reduced (Huismans 2015)
• in animal experiments, an increase in the area, number and insulin content of beta cells was observed (Erdmann 2004)
• glucose production in the liver is reduced (Kleinhans 2005)
• there is no risk of hypoglycaemia (Liebl 2005)

Side effects:

• weight gain of approx. 2 - 3 kg
• the plasma volume increases slightly
• anaemia (Diederich 2020) due to decrease of haemoglobin and haematocrit (Erdmann 2004)
• Increase in:
  • peripheral edema
  • heart failure
• worsening of diabetic macular edema possible
• increased risk of fractures in women
• may cause polycystic ovarian syndrome in premenopausal women
• Recurrent bladder infections and vaginal infections due to increased glucose in the urine (Kasper 2015).

Indications:

As monotherapy in obese patients with type 2 diabetes mellitus and contraindications to metformin in whom appropriate diet and exercise have not resulted in the desired BG reduction (Liebl 2005).

In Germany, glitazones practically no longer play a role due to the sometimes not insignificant side effects (Herold 2020).

Contraindications:

• anamnestically known liver diseases
• Heart failure NYHA III or IV
• Pregnancy (Kasper 2015)
• Lactation (Liebl 2005)
• Bone fractures of postmenopausal women (Diederich 2020)
• Type 1 DM
• Ketoacidosis
• Dialysis patients
• children and adolescents < 18 years
• severe renal insufficiency (Liebl 2005)

Dosage recommendation:

Pioglitazone: e.g. trade name Actos 15 mg or 30 mg tablets.

The daily dose is between 15 - 45 mg (Huismans 2015). Pioglitazone should be administered 1 x / d. In old age and existing mild to moderate renal dysfunction, dose adjustment is not required (Liebl 2005).

The drug can be used both for monotherapy and for combination therapy together with other oral antidiabetic drugs (Huismans 2015).

The combination with insulin is not approved in Germany, as this had led to increased congestive heart failure and pulmonary oedema (Erdmann 2004).

Controls:

Before starting therapy, liver values should be checked according to the manufacturer (Kasper 2015).

During therapy, regular checks of liver enzyme levels are recommended (Huismans 2015).

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2. Diederich S et al (2020) Reference endocrinology and diabetology. Georg Thieme Verlag Stuttgart 491
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