Glitazone

Glitazones belong to the group of oral antidiabetics. In the USA, pioglitazone was approved as the first representative of this group of substances in 1997 (Schwabe 2013).

In 2000, two further drugs came onto the market (Erdmann 2004):

• Troglitazone and
• Rosiglitazone.

As several cases of fulminant liver failure occurred during therapy with troglitazone, the substance was withdrawn from the market again in the USA in March 2005 (Matthaei 2001).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).

Reduction of insulin resistance by binding to the nuclear receptor PPAR- gamma, which is most abundant in adipocytes.

Promoting the redistribution of fat (visceral fat to peripheral sites)

Reduction of 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 hypoglycemia (Liebl 2005)

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

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

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 increasingly led to congestive heart failure and pulmonary oedema (Erdmann 2004).

weight gain of approx. 2 - 3 kg

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 ovary syndrome in premenopausal women

recurrent bladder infections and vaginal infections due to increased glucose in the urine (Kasper 2015)

history of liver disease

heart failure NYHA III or IV

Pregnancy (Kasper 2015)

Lactation (Liebl 2005)

Bone fractures in postmenopausal women (Diederich 2020)

Type 1 DM

Ketoacidosis

Dialysis patients

children and adolescents < 18 years

severe renal insufficiency (Liebl 2005)

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).

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

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

1. Biermann D (2010) Rosiglitazone - market withdrawal effective November 1. Pharmazeutische Zeitung 39
2. Diederich S et al (2020) Reference endocrinology and diabetology. Georg Thieme Verlag Stuttgart 491
3. Erdmann E et al. (2004) Glitazones - an antidiabetic substance class from a cardiological point of view: new aspects for a vascular treatment in diabetes mellitus type 2. Dtsch Arztebl 101 (44): A- 2954 / B- 2499 / C- 2383.
4. Herold G et al (2020) Internal medicine. Herold Publishers 733
5. Huismans H (2005) Encyclopedia of clinical diabetology: practice-oriented interdisciplinary presentation. Deutscher Ärzteverlag Cologne 36
6. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 2414 - 2417
7. Kleinhans R (2005) Significance of peroxisome proliferator-activated receptor γ for the expression of atherogenic scavenger receptors on macrophages and interactions with insulin. Dissertation for the degree of Doctor of Medicine at the Medical Faculty of the Ludwig-Maximilians-University of Munich.
8. Liebl A et al. (2005) Diabetes mellitus type 2. Govi- Verlag Eschborn 65 - 72.
9. Matthaei S et al. (2001) Thiazolidinediones (insulin sensitizers): new aspects in the therapy of diabetes mellitus type 2. Dtsch Arztebl 2001; 98 (14): A- 912 / B- 764 / C- 713.
10. Schwabe U et al. (2013) Arzneiverordnungs-Report 2001: current data, costs, trends and comments. Springer Verlag 52