Alpha-glucosidase inhibitors

- Synonyms

Alpha-glucosidase inhibitors;

First described by

In the 1970s, Puls et al. proposed lowering postprandial blood glucose in diabetics by inhibiting alpha-glucosidase. As a result, the enzyme inhibitor acarbose was developed. In animal experiments with rats, these showed a marked increase in malignant tumours of the urinary tract, which is why further research came to a standstill. Only after the suspicion of carcinogenicity could be dispelled by several studies, testing in humans took place (Mehnert 2003).

The drug "Acarbose" was approved in Germany in 1990. Another representative of the active principle is "Miglitol", which came onto the market in 1998 (Mehnert 2003).

Alpha-glucosidase inhibitors have a very limited significance both in Germany and in the USA (Herold 2020), as no endpoint studies are available to date (Fischer 2007). In the UKPDS (UK Prospective Diabetes Study), the most important study for diabetes treatment, no data were collected for either acarbose or miglitol (Oberdisse 2002).

Alpha-glucosidase inhibitors are intestinal enzyme inhibitors that inhibit alpha-glucosidase in the intestine, thereby delaying the breakdown of carbohydrates and slowing the absorption of glucose (Steinbeck 2005).

Alpha-glucosidase inhibitors are non-insulinotropic, do not cause weight gain (Fischer 2007), and have a low glucose risk (Herold 2020).

Only about 2% of acarbose is absorbed in the intestine. Excretion occurs via the kidney (Mehnert 2003). Miglitol, on the other hand, is absorbed in the small intestine (Frölich 2000) and is also excreted via the kidney (Oberdisse 2002).

Pharmacodynamics (effect)

• inhibit alpha-glucosidase in the small intestine mucosa and thereby delay the breakdown of complex carbohydrates (Diederich 2020)
• postprandial increase in BG is reduced (Herold 2020)
• Reduction of the HbA1c- value is less pronounced than with other oral antidiabetics (Kasper 2015)

Alpha-glucosidase inhibitors do not affect glucose utilization or insulin secretion. They lower the plasma glucose content immediately after the start of therapy (Kasper 2015).

To date, a reduction in cardiovascular events, which has been assumed in the meantime, has not been clearly proven (Diederich 2020).

Indication

The indication is given:

• For the reduction of postprandial BG in type 1 and type 2 diabetics (Kasper 2015). The preferred use is in type 2 DM (Dellas 2018).

Acarbose can be combined with all oral antidiabetics and with insulin (Ludwig 2020), miglitol only with metformin and sulfonylureas. When combined with insulin, significant reductions in HbA1c and postprandial blood glucose levels were observed, with a risk of severe hypoglycemia(Frölich 2000).

Alpha-glucosidase inhibitors are already suitable for the initial therapy of type 2 DM, as they do not increase hyperinsulinemia (Steinbeck 2005).

Since alpha-glucosidase inhibitors are reserved for special situations, they are not considered in detail in the guidelines (Bundesärztekammer 2021).

Dosage and mode of administration

Steinbeck (2005) initially recommends monotherapy. Only later is the combination with oral antidiabetics or insulin indicated.

The dosage should be gradual (Herold 2020). Alpha-glucosidase inhibitors should be taken shortly before the start of a meal, at the beginning of treatment only in the evening. An increase to the maximum dose should be recommended gradually over weeks or months (Kasper 2015).

Dosage recommendation:

- Acarbose 1 - 3 x 50 mg / d (Diederich 2020).

The maximum dose is usually 3 x 50 mg / d (higher doses cause more side effects). However, patients sometimes tolerate doses of up to a maximum of 300 mg / d.

(Herold 2020 / Diederich 2020)

If the HbA1c value cannot be reduced sufficiently with the maximum dose, a combination (see also "Indication") with other oral antidiabetics is recommended (Mehnert 2003).

Adverse effects

Adverse effects are strongly dose-dependent, such as:

• Meteorism
• Flatulence
• Increase in liver enzymes (Herold 2020).

An increase in liver enzymes has only been observed at doses > 600 mg / d in the USA and Israel(Mehnert 2003).

• Diarrhea (due to bacterial breakdown of carbohydrates in the colon [Dellas 2018]).
• Hypoglycemias are possible exclusively in combination therapy (cave: these cannot be treated with disaccharides such as table sugar! [Dellas 2018]). It is essential that the patient is informed about this and always carries glucose (Mehnert 2003).

Gastrointestinal side effects are very common and not infrequently lead to discontinuation of therapy (Ludwig 2020).

Contraindication

• Patients < 18 years of age
• Pregnancy
• Patients with chronic intestinal diseases (Herold 2020)
• Malassimilation
• Metabolic disorders (Steinbeck 2005)
• Hernias
• ileus / subileus (Hien 2013)
• For Miglitol:
  • Renal insufficiency (Oberdisse 2002)

Interactions

Alpha-glucosidase inhibitors can increase the sulfonylurea level and thus increase the risk of hypoglycemia. In this case, early dose reduction of the sulfonylureas may be indicated.

Simultaneous treatment with antacids and bile acid resins should be avoided (Kasper 2015).

Preparations

• Acarbose (Herold 2020)

Trade name: Glucobay ® (Steinbeck 2005)

• Miglitol (Ludwig 2020)

Trade name: Diastabol ®

Both preparations are available in tablet form of 50 or 100 mg (Steinbeck 2005).

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