Pharmacological possibilities of influencing diabetes

Non - pharmacological therapy

 * diet
 * physical activity
 * bariatric treatment

Oral antidiabetics
Oral antidiabetics (PADs) are drugs used in the treatment of diabetes mellitus. The mechanism of their action depends on the production of endogenous insulin and therefore cannot be used in patients with type 1 diabetes.

According to the place of operation, PAD can be divided into 4 groups:


 * insulin sensitisers - increase the sensitivity of cells to insulin (biguanides, thiazolidinedionesState Office for Drug Control ATC group: A10BG);
 * insulin secretagogue - increase insulin delivery from pancreatic β-cells (sulfonylurea derivativesState Office for Drug Control ATC group: A10BB, glinides);
 * intestinal glucosidase inhibitors - reduce intestinal glucose absorption - alpha-glucosidase inhibitorsState Drug Administration ATC Group: A10BF;
 *  proximal tubule glucose reuptake inhibitors - increase glycosuria (gliflosins).

Insulin sensitizers
They increase the sensitivity of cells to insulin. They do not cause hypoglycaemia and are therefore referred to as "euglycaemic drugs"

Biguanides

Metformin is the basic PAD today. It is well tolerated and can be advantageously combined with other antidiabetics. It reduces cardiovascular mortality by 50% and has positive late effects of treatment (it is advisable to start treatment already in the period of prediabetes). It does not cause weight gain (unlike secretagogues and thiazolidinediones), so it is also beneficial for obese patients.[2] It is a cheap drug without a prescription restriction.

 Mechanism of action 

They increase the sensitivity of tissues (especially liver and skeletal muscle) to insulin and reduce blood glucose:


 * promoting glucose utilization in skeletal muscle and adipose tissue (by stimulating glycolysis),
 * attenuation of gluconeogenesis in the liver,
 * by reducing the absorption of glucose from the gut.

Side effects

They support glycolysis and thus lactate production. Thus, lactic acidosis can be a serious complication. Individuals with failing kidneys, cardiopulmonary insufficiency, liver insufficiency (alcoholics) are predisposed to this. In these cases, biguanides are contraindicated.

Gastrointestinal problems may occur at the beginning of treatment.

Intravenous administration of an iodinated contrast agent may lead to renal failure. This may cause accumulation and increase the risk of lactic acidosis. Therefore, biguanide use must be discontinued 48 hours before the examination. They are also discontinued before surgery.

They are not recommended for the treatment of diabetes during pregnancy. Insulin should be used to maintain blood sugar levels to minimize the risk of fetal malformations.

Thiazolidinediones

Mechanism of action

They have similar effects as biguanides. Through the nuclear receptor, PPAR-γ activates the transcription of genes responsible for carbohydrate and fat metabolism.

Side effects

They cause mild fluid retention (therefore diuretics are sometimes added), therefore they are not used in patients with heart failure, edema conditions, during pregnancy. Pioglitazone is contraindicated in haematuria of unclear origin. They require regular liver function tests. There is often an increase in weight (fluid retention, increase in adipose tissue). An eye examination is also appropriate before use, due to the risk of worsening diabetic macular edema.

Today, only one pioglitazone is used (rosiglitazone does not have a beneficial effect on cardiovascular mortality and is currently withdrawn from the market [4]), it is well tolerated, it is suitable for the contraindication of metformin.

Insulin secretagogue
They increase insulin delivery from pancreatic β-cells.

They are risky in terms of possible induction of hypoglycemia and cause weight gain.

Sulphonylureas Mechanism of action Increased insulin release from pancreatic β-cells is achieved by blocking ATP-sensitive K + channels in the membrane. This reduces the flow of potassium from the cell, depolarizes the membrane and opens Ca2+ channels. Penetrating Ca2+ ions cause insulin to wash out.

Side effects The most serious complication may be hypoglycaemia, especially with longer-acting substances. This group of drugs also increases appetite, so treatment is often associated with weight gain.

Drugs II are used in practice. generation (glipizide) and III. generation (glimepiride). Most often in combination therapy with metformin (especially in case of insufficient compensation of type II DM monotherapy with metformin).

Glinides Newer drugs also block the ATP-sensitive K + channel in β-cell membranes. They work quickly, making them ideal for use with food to compensate for postprandial hyperglycemia. Examples of substances are repaglinide and nateglinide.

Intestinal glucosidase inhibitors
They are used to control postprandial hyperglycemia. The basic substance used in this group is acarbose.

Mechanism of action

By inhibiting enzymes, they reduce and slow down the absorption of carbohydrates in the small intestine. The blocked enzyme does not cleave them and therefore cannot be resorbed (absorption of monosaccharides remains unchanged).

Side effects

Flatulence, diarrhea and abdominal pain caused by the action of microbial intestinal flora on undigested compound carbohydrates.

If a patient develops hypoglycaemia due to other medications, they cannot be treated orally with sucrose but only glucose.

Gliflozins
Mechanism of action

They inhibit the SGLT-2 transporter in the proximal tubule of the nephron, thereby blocking glucose reuptake and increasing glycosuria. Thus, the renal threshold for glucose is shifted and blood glucose is lowered. Increased glucose losses lead to energy loss and weight loss. At the same time, they reduce glycated hemoglobin, uricaemia, slightly increase HDL cholesterol and, due to osmotic diuresis, a slight decrease in blood pressure.

Side effects

Increasing the frequency of urogenital tract infections. These are most often fungal infections in women. Due to increased diuresis, caution should be exercised in patients at risk of hypotension or volume depletion.

The risk of hypoglycaemia is minimal with gliflozin.

In the Czech Republic dapagliflozin, canagliflozin and empagliflozin, is available.

Incretins
Incretin-modulating agents can now be used in the treatment of type 2 diabetes. They are very effective, safe, but expensive. They increase insulin secretion, inhibit glucagon and act only in hyperglycemia.

Exenatide is a synthetic analogue of GLP-1 (glucagon-like peptide 1), an analogue of incretins. It applies s. C., So it does not belong to the PAD.

Dipeptidyl peptidase 4 (DPP-4) inhibitors block an enzyme that inactivates endogenous incretins. They are less effective than incretin analogues, but are cheaper and orally administrable. Example of a substance: sitagliptin, inagliptin.

Related Articles

 * Diabetes mellitus
 * Type 1 diabetes mellitus (endocrinology)
 * Type 1 diabetes mellitus (biochemistry)
 * Type 2 diabetes mellitus (endocrinology)
 * Type 2 diabetes mellitus (biochemistry)
 * Insulin

Reference

 * 1) CZECH, Richard, et al. Internal. 1st edition. Prague: Triton, 2010. 855 pp. 233. ISBN 978-80-7387-423-0.
 * 2) TREVOR, Anthony J. Katzung & Trevor's pharmacology: examination & board review. 10th ed. New York: McGraw-Hill Medical, c2013. a LANGE medical book. ISBN 978-0-07-178923-3.
 * 3) SUCHOPÁR, Josef, VALENTOVÁ, Štěpánka, ed. Remedia compendium. 4th edition Prague: Panax, 2009. ISBN 978-80-902806-4-9.
 * 4) SCHEEN, A J. [Suspension of the commercialization of sibutramine and rosiglitazone in Europe]. Rev Med Liege [online]. 2010, vol 65, no. 10, pp. 574-9, also available from . ISSN 0370-629X.
 * 5) SANUSI, Himawan. The role of incretin on diabetes mellitus. Acta Med Indones [online]. 2009, vol 41, no. 4, pp. 205-12, also available from . ISSN 0125-9326.

Used literature
