Glucosidase inhibitor. Oral hypoglycemic drugs: list, principle of their action

General characteristics. Application.

Alpha-glucosidase inhibitors are pseudotetrasaccharides that, competing with di-, oligo- and polysaccharides for binding sites on digestive enzymes (sucrase, glycoamylase, maltase, dextrose, etc.), slow down the processes of sequential fermentation and absorption of carbohydrates throughout the small intestine. This mechanism of action leads to a decrease in the level of postprandial hyperglycemia, i.e., drugs in this group are antihyperglycemic, not hypoglycemic. Thus, they are most effective when glycemia is high after a meal and normal in the fasting state. The effectiveness of these drugs is low and occurs mainly in patients with newly diagnosed type 2 diabetes mellitus.

The side effects of alpha-glucosidase inhibitors are not dangerous, but can be very unpleasant for patients. The large intestine receives a significantly larger amount of carbohydrates than usual, which are processed by the bacterial flora with significant gas formation. Patients experience flatulence and diarrhea. Hypoglycemia does not develop during therapy with alpha-glucosidase inhibitors. However, it should be taken into account that if hypoglycemia has developed for other reasons (overdose of sulfonylurea drugs), the absorption of carbohydrates taken orally to correct it slows down. Patients should be informed that in this situation they must take medications or products containing glucose: grape juice, glucose tablets.

Guar gum (Guarem)

Guar gum is a dietary fiber obtained from the endosperm of Cyamopsistetragonolobus seeds. Guar gum is a polysaccharide that forms a viscous gel with water; it significantly prolongs gastric emptying, as well as the absorption of carbohydrates in the small intestine, thereby reducing glucose levels and insulin concentrations. With long-term use, it reduces the initial blood glucose level by approximately 1–2 mmol. It is used for diabetes mellitus in adults, in which the initial intake of oral hypoglycemic drugs did not achieve a sufficient therapeutic effect, and in cases where it is impossible to switch to therapy with a combination of sulfonylurea derivatives and biguanides. In poorly controlled adult diabetes mellitus, in which, despite optimal therapy with oral hypoglycemic drugs, even minimal effect is not achieved, and in cases where transfer to insulin therapy is undesirable.

Thiazolidinediones (glitazones)

They are used for type 2 diabetes mellitus when diet therapy is ineffective, both as monotherapy and in combination with sugar-lowering drugs of other groups. The action of drugs in this group is aimed at increasing the sensitivity of tissue cells to insulin. Thus, they reduce insulin resistance.

In modern medical practice, two drugs of this group are used: Rosiglitazone and Pioglitazone.

They reduce insulin resistance by increasing the synthesis of glucose transport cells. Their action is possible only if you have your own insulin. They lower the level of triglycerides and free fatty acids in the blood.

Pharmacokinetics:

The drugs are quickly absorbed into the gastrointestinal tract. Maximum concentrations in the blood are reached 1-3 hours after administration. Metabolized in the liver. Pioglitazone forms active metabolites, which ensures a longer action. Excreted mainly by the kidneys.

Contraindications:

Diabetes mellitus type 1; pregnancy and lactation; liver diseases during exacerbation; Alanine aminotransferase (ALT) level exceeding the norm by 2.5 times or more; age under 18 years.

Side effects:

There have been cases of increased ALT levels, as well as the development of acute liver failure while taking thiazolidinediones. It is necessary to evaluate liver function before starting medication.

Taking thiazolidinediones may contribute to weight gain. This is observed both in monotherapy and in combination of thiazolidinediones with other drugs. Most likely, this is due to the accumulation of fluid in the body. It not only affects weight gain, but also causes edema and deterioration of cardiac activity. For severe edema, it is advisable to use diuretics.

Meglitinides ("glinides")

Nateglinide is a derivative of D-phenylalanine. Unlike other oral hypoglycemic agents, the effect of nateglinide on insulin secretion is more rapid but less persistent. Nateglinide is used primarily to reduce postprandial hyperglycemia in type 2 diabetes. These are prandial glucose regulators and cause an increase in insulin secretion by acting on the beta cells of the pancreas.

Two drugs of this group are used -

Repaglinide (Novonorm) and Nateglinide (Starlix).

Indications for use: non-insulin-dependent diabetes mellitus when diet is ineffective.

Stimulates insulin production; their action is aimed at reducing prandial hyperglycemia, that is, hyperglycemia after eating; They are not suitable for reducing fasting sugar.

Pharmacokinetics:

The hypoglycemic effect of the drugs begins 7-15 minutes after taking the tablet. The effect of these drugs does not last long; they must be taken several times a day. They are eliminated primarily by the liver.

Contraindications:

Diabetes mellitus is insulin dependent; pregnancy and lactation; age under 18 years; chronic kidney and liver diseases.

Side effects:

Nausea, rarely vomiting, diarrhea or constipation. Sometimes allergic reactions occur in the form of urticaria and itching.

Incretin mimetics.

Incretins are hormones that are secreted by certain types of cells in the small intestine in response to food intake and stimulate the secretion of insulin.

They increase glucose-dependent insulin secretion, improve β-cell function, suppress excess glucagon secretion, slow gastric emptying, and reduce appetite.

Incretin mimetics: direct exenatide (Byeta) and indirect gliptins.

Exenatide, a glucagon-like peptide, enhances insulin secretion and produces other incretin effects. Prescribed subcutaneously for type II diabetes in addition to metformin or its combination with sulfonamides to improve hypoglycemia control.

Not prescribed for type I diabetes, diabetic ketoacidosis, kidney failure, severe gastrointestinal diseases, pregnancy, lactation, under 18 years of age. There may be hypoglycemia, migraine, anorexia, weakness, drowsiness.

Gliptins—valdagliptin (glavus) and sitagliptin (Januvia) block dipeptidyl peptidase subtype 4, which hydrolyzes incretins. Prescribed (monotherapy) orally regardless of food intake for type II diabetes in addition to diet and exercise to improve hypoglycemia control; if diet and physical activity during treatment with metformin or insulin sensitizers do not adequately control hypoglycemia, sitagliptin is combined with these drugs.

Not prescribed for type I diabetes, diabetic ketoacidosis, under 18 years of age, pregnancy and lactation. Nausea and diarrhea are possible.

INSULINS

Insulin is a hormone that is produced in the pancreas. It actively participates in metabolism, enhances the synthesis of proteins and fats, and most importantly, regulates blood glucose levels. Its lack threatens a person with coma and death. Therefore, people with type 1 diabetes (with absolute insulin deficiency) need to take the hormone daily. Some patients with type 2 diabetes also need such therapy.

Numerous insulin preparations currently used differ from each other in duration of action, degree of purification, as well as type (preparations of porcine insulin, cattle and human insulin).

The listed insulins differ from each other in amino acid sequence. Thus, beef insulin differs from human insulin in three amino acids, while pork insulin differs in only one amino acid. Therefore, pig insulin has less antigenic activity compared to beef insulin, the introduction of which produces high titer antibodies, leading to the formation of corresponding immune complexes, which, as numerous scientific studies have shown, are involved in the pathogenesis of late complications of diabetes. It is for this reason and in accordance with the requirements of the pharmacopoeia of various countries, including the pharmacopoeia of the Russian Federation, that it is recommended to use only monocomponent preparations of pig and human insulin for the treatment of patients with diabetes.

Numerous insulin preparations available on the market and registered with the Ministry of Health of the Russian Federation differ in their action: short-acting preparations; intermediate-acting and long-acting drugs. Short-acting and fast-acting insulin preparations (onset of action 30 minutes after administration; maximum action between 2-3 hours after administration and duration up to 6 hours) include: Actrapid MS and NM (Novo-Nordisk), Iletin-P-regular and Humulin-regular (Eli-Lilli), Insuman-normal (Hoechst), Berlinsulin N-normal (Berlin-Chemie), Insulrap SPP (Pliva), etc. Humalog (Eli-Lilli) has a faster onset (after 10-15 minutes after administration) and a shorter overall duration of action (3-4 hours) compared to simple insulin.

Medium-acting drugs include: Protophan MS and NM (Novo-Nordisk), Humulin-basal or NPH, Lenta, Il-letin-2 (Eli-Lilly), Insuman-basal (Hoechst), Berlinsulin N-basal (Berlin- Hemi). The onset of action of the drugs is 2 hours after administration; maximum effect after 8-10 hours and duration of action 18-24 hours.

Long-acting drugs include: Ultratard NM (Novo-Nordisk), Humulinultralenta (Eli-Lilly). The onset of action of the drug is 4-5 hours after administration; maximum effect after 8-14 hours and duration of action 24-36 hours.

There are several treatment regimens for diabetes mellitus using various insulin preparations. From 1920 to 1930, only short-acting insulin preparations were used. In 1940, in connection with the development of protamine-zinc insulin, a scheme for its use in combination with short-acting insulin was proposed. From 1960 to 1965, most clinicians recommended using short-acting and medium-duration insulin (lenta, long, isophane, protophan, etc.) in the morning and evening or 3 times a day before meals, short-acting insulin, and at night semilenta insulin (semilong ). Since 1980, it has been more widely recommended to administer short-acting insulin 3 times during the day, and at 10 or 11 p.m. an injection of medium-acting insulin (protophan, basal, etc.) or long-acting insulin (ultratard). This type of therapy is called intensive insulin therapy. Intermediate-acting or long-acting insulin preparations can be administered 2 times a day.

The development of long-acting insulin preparations was caused by the need to relieve the patient from frequent injections of short-acting insulin, since each injection is associated with a negative emotional reaction to pain, as well as with certain difficulties in maintaining aseptic and antiseptic conditions during repeated injections at home.

Due to the presence of a large number of insulin preparations from various manufacturers (firms) on the domestic market, it is necessary to especially emphasize the need to use a combination of short-acting insulin preparations with an average duration of production from the same company. This is due to the fact that different companies use various additives as preservatives and other essential components, which can interfere with each other and have undesirable effects on the body.

Practice shows that intensive insulin therapy makes it possible to achieve long-term compensation of diabetes over a long period of time, which is an indispensable condition for the prevention of late vascular complications of diabetes.

Research was carried out on the creation of insulin preparations, the use of which contributed, on the one hand, to stable compensation of diabetes, and on the other, to a reduction in the number of insulin injections. Thus, double-peak, mixed or combined action insulin preparations were obtained. Such drugs are a different combination of short-acting insulin and intermediate-acting insulin. Eli Lilly produces combined action insulins under the name “profiles”. There is profile No. 1, which consists of 10% short-acting insulin (regular or normal) and 90% NPH or isophane insulin; as well as profile No. 2, No. 3, and No. 4. But there is a drug "Actrofan NM", which is a mixture consisting of 30% short-acting insulin and 70% protophan. All drugs of combined action must be thoroughly mixed before injection until a homogeneous suspension is obtained.

In the early 80s, the Novo-Nordisk company introduced doctors and patients to the Novopen-1 pen, which quickly gained popularity due to a number of conveniences. Firstly, the pen was equipped with a special thin needle with double laser sharpening, which makes injecting insulin using a pen almost painless. The use of thermostable insulin in penfils made it possible to carry a syringe pen filled with penfil with you without fear of insulin destruction under the influence of ambient temperature and a decrease in its biological activity for 30 days. And thirdly, there was no need to carry a sterilizer with sterile syringes and a bottle of insulin (or 2 bottles of insulin of varying durations of action), which made the patient’s life much easier.

Currently, this company produces syringe pens "Novopen-1, Novopen-2 and Novopen 3. The latter uses a 3 ml insulin cartridge. Domestic production is represented by syringe pens "Crystal-3", "Insulpen" and "Insulpen-2 ". These syringe pens allow the use of insulin vials, which greatly facilitates treatment (no dependence on the availability of cartridges), allows you to prepare and use mixed insulin preparations individually (any proportion of short- and medium-acting insulin).

As mentioned above, combined-acting insulin preparations are available not only in penfils, but also in regular bottles containing appropriate combinations of proportions of short- and medium-acting insulin. In addition, the patient can individually prepare various combined insulins containing short- and medium-acting insulin in any proportion. Such combination mixtures of insulin preparations can be obtained by mixing short-acting insulin and intermediate-acting insulin: NPH, isophane, basal or protophan. Such individually selected “mixtures” of combined-action insulin preparations can be used using conventional insulin syringes or using domestically produced syringe pens “Insulpen”.

Great hopes for achieving strict diabetes compensation were pinned on the use of insulin dispensers. If in a biostator the rate of insulin infusion depends on its level in the blood, i.e. While a biostator operates on the principle of a closed system with feedback, in insulin dispensers there is no such feedback and the rate of insulin infusion is set by each patient individually depending on his activity and meal time. This circumstance naturally restrains their widespread use. The second inconvenience is due to the fact that when using an insulin dispenser, it is necessary to change the location of the needle daily due to the possible addition of a secondary infection and a violation of the rate of insulin absorption. However, recently special catheters have been manufactured for subcutaneous insulin infusion, allowing their use for several days. In this case, the absorption of insulin from the injection site remains unchanged for several days, diabetes control remains at a sufficient level while reducing the amount of insulin required to maintain stable diabetes compensation. The use of such catheters allows insulin to be administered intraperitoneally. The last aspect is very important, since it is known that about 50% of insulin administered intraperitoneally is absorbed in the portal vein system and reaches the liver, where insulin has its main hypoglycemic effect. With the subcutaneous administration of insulin, according to many researchers, the development of the atherosclerotic process occurs.

Insulin needleless injectors offer some promise for administering insulin. But they are almost never used due to their high cost. In this case, insulin is injected under high pressure into the subcutaneous tissue. Such injectors have been used for a long time to vaccinate large groups of the population (smallpox and other infections). However, such injectors are very bulky and enormous efforts and resources were required to develop customized insulin injectors.

Complex sugars that enter the gastrointestinal tract with food are initially broken down in the intestines into simple sugars with the help of enzymes. Acarbose acts as a “food trap” by competitively and reversibly binding to the small intestinal enzyme (alpha-glucosidase) involved in the digestion of carbohydrates. And since the enzyme is occupied by acarbose, poly- and oligosaccharides supplied with food are not broken down and are not absorbed. This prevents the development of postprandial hyperglycemia.

pros

Acarbose does not cause an increase in blood insulin levels (therefore, there is no risk of hypoglycemia).
Due to the fact that acarbose interferes with the absorption of carbohydrates, body weight decreases to one degree or another (as the calorie content of food decreases).
According to studies, long-term therapy with acarbose is accompanied by a significant reduction in the progression of vascular atherosclerosis.
Acarbose is not absorbed and therefore has no systemic effects.

Minuses

Carbohydrates that are not subject to enzymatic processing cause fermentation in the large intestine, which can be accompanied by flatulence and diarrhea. But this is not a side effect, it is the result of the action of the drug itself against the background of a diet disorder.
Acarbose has less hypoglycemic activity than metformin or sulfonylurea derivatives and reduces HbA 1C by 0.5–0.8%

Indications

Diabetes mellitus type 1 (as part of combination therapy). Acarbose is the only oral antidiabetic drug that can be used for type 1 diabetes.
Diabetes mellitus type 2.
Prevention of type 2 diabetes mellitus. Acarbose is the drug of choice for individuals with prediabetes, which is accompanied by postprandial hyperglycemia at normal fasting levels.

Contraindications and side effects

Contraindications include: liver cirrhosis; acute and chronic inflammatory bowel diseases, especially complicated by digestive and absorption disorders, intestinal strictures and ulcers, increased gas formation; chronic renal failure; pregnancy and breastfeeding.

Side effects are rare: increased levels of transaminases (ALT and AST), intestinal obstruction, jaundice. Allergic reactions: skin rash (including urticaria), skin hyperemia.

Directions for use and doses

Acarbose is taken immediately before (or during) meals.

The initial dose is 50 mg 3 times a day. The dose is slowly (at 4-8 week intervals) increased taking into account individual tolerance. The target dose for an adult weighing more than 60 kg is 300 mg/day. in three steps. The maximum dose is 600 mg/day.

The effect of acarbose depends on the dose: the higher the dose, the fewer carbohydrates are broken down and absorbed in the small intestine. However, increasing the dose to more than 300 mg/day. although it is accompanied by a further (albeit weakly expressed) decrease in postprandial hyperglycemia, it simultaneously increases the risk of an increase in the concentration of AST and ALT in the blood.

Treatment with acarbose should be carried out under the control of the level of glycosylated hemoglobin and transaminases in the first year of treatment - once every 3 months, then periodically.

Precautionary measures

During treatment with acarbose, carbohydrate intake should be limited. Flatulence and diarrhea that occur during treatment reflect the pharmacological effect of the drug and are a consequence of violation of dietary recommendations. Acarbose itself is not absorbed and, accordingly, does not produce systemic effects.

Acarbose can be combined with other glucose-lowering agents. However, you should be aware that acarbose enhances the hypoglycemic effect of other oral drugs used, which requires adjustment of their dose (downward). If this condition is not met, hypoglycemia may develop, which can only be stopped by taking pure glucose, since taking complex carbohydrates will have no effect during treatment with acarbose.

When used together with antacids, sorbents and enzymes that improve the digestion process, the effectiveness of acarbose is significantly reduced.

File contents Oral hypoglycemic therapy

Alpha-glucosidase inhibitors - acarbose (Glucobay).

Oral hypoglycemic therapy

2. Acarbose (Glucobay)

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Alpha glucosidase inhibitors

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Unlike other antidiabetic drugs, the hypoglycemic effect of alpha-glucosidase inhibitors is outside the spectrum of hormonal regulation of carbohydrate metabolism (insulin/glucagon primarily) - they disrupt the absorption of carbohydrates from the intestine. As a result, after a meal, postprandial glycemia decreases and, secondary to it, postprandial hyperinsulinemia. Since not only hyperglycemia, but also hyperinsulinemia reduces the risk of cardiovascular complications of T2DM, it is believed that this latter effect is an additional advantage of treatment with alpha-glucosidase inhibitors compared with insulin secretagogues.

10%) that this does not affect the effect of lactose. Acarbose also inhibits pancreatic amylase, but Miglitol does not. But the clinical effects of these drugs are the same. Since, unlike Acarbose, Miglitol is absorbed, its systemic effects on metabolic processes have been studied. It turned out that it suppresses glycogenolysis in liver tissue in vitro. At the same time, the manufacturers of Miglitol did not detect any systemic action in the body, despite absorption.

Acarbose reduces the risk of cardiovascular complications, and when prescribed to patients with early disorders of carbohydrate metabolism, it can normalize it and reduce the risk of developing overt diabetes mellitus. The mechanism of this action of Acarbose is still unclear, but by studying the kinetics of glucose in an intravenous glucose tolerance test, we were able to show that in early disorders of carbohydrate metabolism (IGT, IGN), it does not affect the production of glucose by the liver and the elimination of glucose in persons in whom treatment Acarbose led to the normalization of previously impaired carbohydrate metabolism (NGN or IGT). That is, Acarbose eliminates early metabolic disorders without interfering with the intimate processes of the pathogenesis of T2DM, which is probably natural, given the “extraendocrine” mechanism of its action.

Pharmacokinetics. After administration, Acarbose is practically not absorbed in the intestine - the bioavailability is 1-2% and the peak concentration in the blood is observed within 1 hour, from where it is excreted unchanged by the kidneys. Metabolism of Acarbose occurs exclusively in the intestine. Under the influence of natural intestinal flora and digestive enzymes, at least 13 metabolites are formed from Acarbose, the bioavailability of which is already

34% and they are absorbed an hour after formation in the intestine. Only one of the alpha-glucosidase metabolites retains its inhibitory effect on alpha-glucosidases.

The peak concentration of Miglitol after administration occurs in the blood within 3 hours and the half-life is 2-3 hours. Its absorption depends on the dose: the higher it is, the less it is.

95%. But since the point of its action is the villi of the small intestine, the absorption of Miglitol does not in any way affect the glucose-lowering effectiveness of the drug. Miglitol is excreted unchanged from the blood by the kidneys, and the drug remaining in the intestines is excreted in the feces, also unchanged. Miglitol is not metabolized in the body.

Interaction with other drugs. When combined therapy with alpha-glucosidase inhibitors with insulin or other antidiabetic drugs, the hypoglycemic effect of the latter may be enhanced, causing hypoglycemia. In these cases, the dose of any glucose-lowering drug in the combination should be reduced. Any drugs that increase blood glucose levels, such as thiazide diuretics, corticosteroids, oral contraceptives, and estrogens, niacin, phenothiazides, thyroid hormones, and calcium channel blockers may reduce the effectiveness of alpha-glucosidase inhibitors. Although miglitol reduces the degree of absorption and the peak concentration of glibenclamide and metformin, this does not manifest itself clinically. Acarbose reduces the bioavailability of metformin, but this does not affect its effectiveness. Acarbose does not interact with digoxin, nifedipine, propranolol or ranitidine. Since in very large doses Acarbose causes an increase in liver enzymes, it is undesirable to combine it with paracetamol (a known liver toxin), especially in people who abuse alcohol. Miglitol reduces the level of digoxin in the blood, as well as the bioavailability of propranolol and ranitidine, but does not interact with nifedipine, antacids or warfarin. Activated charcoal and digestive enzymes such as amylase and pancreatin may interfere with the action of alpha-glucosidase inhibitors locally in the intestine.

Drugs, doses and treatment regimens. It should be noted that in many patients, in order to avoid side effects, treatment with an alpha-glucosidase inhibitor should be started with one tablet per day at a dose of 25 mg. The drug should be taken at the beginning of a meal, with the largest meal, which must contain complex carbohydrates (alpha-glucosidase inhibitors act only in the presence of polysaccharides in food). The dose is then increased by 25 mg/day and no more than once a week until it is prescribed with all main meals. The maximum dose (300 mg) may be prescribed, but it should be borne in mind that increasing the dose above the average usually gives a slight glucose-lowering increase, and side effects increase proportionally and significantly with increasing dose. Typically a dose of 50 mg 3 times daily produces maximum effect.

GLUCOBAY

(B AYER SCHERING PHARMA, Germany) – Acarbose, 50 or 100 mg tablet. The initial dose is mg 3 times a day with carbohydrate-containing food. If treatment is insufficiently effective after 4-8 weeks of therapy, the dose can be increased to 200 mg 3 times a day. Maximum daily dose mg. The average daily dose is 300 mg (2 tablets of 50 mg or 1 tablet of 100 mg 3 times a day). The tablet should be taken whole, without chewing, with a small amount of water, immediately before meals or chewed with the first portion of food.

DIASTABOL

(BAYER AG, Germany) – Miglitol, 50 or 100 mg tablet. The initial dose is 25 mg 3 times a day with food; if necessary, the dose is increased to 50 mg 3 times a day with an interval of 4-8 weeks; maximum dose 100 mg 3 times a day. It should be noted that although the drug was registered in Russia by BAYER AG in 1998 and is present in Russian drug reference books (though without indicating the manufacturer and in the form of “Miglitol”), it is actually not used in clinical practice. On the Russian Internet it is offered for purchase, but the manufacturer is usually not indicated on the Sites, and if it is listed, it is not BAYER. So endocrinologists should continue to exercise some caution regarding its use in Russia.

Indications. Acarbose, as well as Miglitol, can be prescribed to patients with T2DM as initial monotherapy or in combination with other hypoglycemic drugs - metformin, sulfonamides or insulin. Several extensive studies with Acarbose, including the large post-marketing PROTECT (Precose Resolution of Optimal Titration to Enchance Current Therapies) study, which included more than 6,000 diabetic patients, showed that treatment with Acarbose reduced HbA 1c levels by 0.6- 1.1%, postprandial glycemia - by 2.2-2.8 mmol/l, and fasting glycemia - by 1.4-1.7 mmol/l.

In small and short-term studies of the effectiveness of Miglitol, a decrease in HbA 1c was found by 0.4-1.2%, postprandial glycemia by 1.1-3.3 mmol/l and a slight decrease in postprandial hyperinsulinemia.

The clinical effectiveness of both drugs is believed to be comparable, although no special comparative studies have been conducted, which does not allow us to objectively highlight any advantages of each of them. Age does not affect the effectiveness of treatment. Despite suppressing carbohydrate absorption, the drugs do not cause weight loss.

In Russia, only Acarbose is used, although not very often. Reasons for this may be the need to titrate the dose of alpha-glucosidase inhibitors over weeks to eliminate the possibility of side effects, as well as the more noticeable hypoglycemic effect of other antidiabetic drugs.

Contraindications and restrictions. Although alpha-glucosidase inhibitors themselves do not cause hypoglycemia, they can enhance the hypoglycemic effect of sulfonamides or insulin if combined with them. In the case of hypoglycemia that develops while taking alpha-glucosidase inhibitors, it should be eliminated exclusively by taking monosaccharides, glucose in particular. Taking complex carbohydrates (sandwich, etc.) in this case is less effective because alpha-glucosidase inhibitors reduce the degree of digestion of complex carbohydrates in the gastrointestinal tract. Since alpha-glucosidase inhibitors are excreted by the kidneys, especially Miglitol, they are contraindicated in patients with creatinine clearance levels<25 мл/мин. Больным с нарушением функции печени не нужно модифицировать дозу ингибиторов альфа-глюкозидазы, так как они не метаболизируются в печени. Вместе с тем, больным с циррозом печени Акарбозу назначать не рекомендуется из-за частых желудочно-кишечных побочных действий (вздутие живота и т.п.).

It is not recommended to prescribe these drugs to pregnant women, since their safety in pregnant women has not been studied and since they are excreted in small quantities in milk, they are not prescribed to breastfeeding women.

Acarbose and Miglitol are contraindicated in case of hypersensitivity to them, diabetic ketoacidosis, and plasma creatinine<2,0 мг% (176 ммоль/л) и следующих болезнях органов пищеварения:

Inflammatory bowel diseases

Partial intestinal obstruction

Chronic intestinal diseases that are accompanied by significant disruption of the processes of digestion and/or absorption or in conditions that are aggravated by increased formation of gases in the intestines

In some patients, during treatment with acarbose at a high dose (≥100 mg / 3 times a day), an increase in the level of liver enzymes was observed, which returned to normal after discontinuation of the drug. It is therefore recommended to monitor liver enzymes every three months during the first year of treatment with alpha-glucosidase inhibitors and reduce the dose or discontinue them if liver enzyme levels increase

Oral hypoglycemic drugs: list, principle of their action

Treatment for type 1 and type 2 diabetes mellitus has significant differences. In type 2 diabetes, the function of insulin synthesis is preserved, but it is produced in reduced quantities. At the same time, tissue cells become less susceptible to the hormone. These disorders can be successfully corrected with oral hypoglycemic drugs.

Types of oral glucose-lowering medications

There are many hypoglycemic drugs available, they differ from each other in their origin and chemical formula. The following groups of oral hypoglycemic agents are distinguished:

sulfonylurea derivatives;
glinides;
biguanides;
thiazolidinediones;
α-glucosidase inhibitors;
incretins.

In addition, a new group of hypoglycemic drugs has recently been synthesized - derivatives of sodium-glucose cotransporter type 2 (SGLT2) inhibitors.

Biguanide derivatives

Currently, the only biguanides used are metformin. In fact, this medicine does not affect the synthesis of insulin, and therefore will be completely ineffective if insulin is not synthesized at all. The drug realizes its therapeutic effect by increasing the utilization of glucose, improving its transport through cell membranes, as well as reducing glucose in the blood.

In addition, the drug has an anorexigenic effect, and therefore can be used in the treatment of obesity under the supervision of a physician. By the way, some “miracle pills” for weight loss contain this substance, although an unscrupulous manufacturer may not indicate it in the composition. The use of such drugs can be truly dangerous to health. Metformin is an antidiabetic drug that is prescribed by a doctor taking into account indications and contraindications.

Contraindications to the use of biguanides:

If a woman taking metformin becomes pregnant, she should stop using this medication. The use of metformin will be possible only after stopping breastfeeding.

Sulfonylurea derivatives

Very often, in the treatment of type 2 diabetes, they resort to the use of sulfonylurea derivatives. There are three generations of sulfonylurea drugs:

First generation: tolbutamide, tolazamide, chlorpropamide.
Second generation: glibenclamide, glisoxepide, gliquidone, glipizide.
Third generation: glimepiride.

First generation drugs have actually lost their relevance, and therefore are now practically not used. Second- and third-generation drugs are several tens of times more active than first-generation drugs. In addition, the likelihood of developing side effects when using more modern sulfonylurea drugs is much less. The first drug of the second generation was glibenclamide, which is successfully used now.

Sulfonylureas have varying degrees of effect and duration of action. Among them, glibenclamide has the most pronounced hypoglycemic effect. Perhaps this is the most popular representative among sulfonylurea drugs. The second most frequently used is gliclazide. This medicine not only has a hypoglycemic effect, but also has a positive effect on the rheological properties of the blood, as well as microcirculation.

Sulfonylurea derivatives stimulate insulin secretion and release from beta cells, and also restore the sensitivity of these cells to glycemia.

Not effective if the patient has significant loss of pancreatic beta cells;
In some patients, for unknown reasons, it does not have an antidiabetic effect;
Effective only if you follow a diet;
Must be taken half an hour before meals.

The main contraindications to the use of sulfonylurea drugs are type 1 diabetes mellitus, ketoacidosis, pregnancy and lactation, and major operations.

Alpha-glucosidase inhibitors

This group is represented by drugs acarbose And miglitol. They reduce the intestinal absorption of most carbohydrates (maltose, sucrose, starch). As a result, preventing the development of hyperglycemia. The use of alpha-glucosidase inhibitors can cause all sorts of dyspeptic symptoms (flatulence, diarrhea) due to disruption of the digestion processes and absorption of carbohydrates. To avoid undesirable effects from the digestive tract, treatment begins with small doses, gradually increasing it. The tablet must be taken with food. In addition, it is important to follow a diet and limit the intake of complex carbohydrates.

In the event of dyspeptic symptoms, one should not resort to the use of enzymatic preparations, antacids, or sorbents. This, of course, will improve digestion, eliminate flatulence and diarrhea, but the effectiveness of the alpha-glucosidase inhibitor will noticeably decrease.

Acarbose is the only oral agent that can be used in the complex treatment of insulin-dependent diabetes. In addition, according to modern research, treatment with acarbose is accompanied by a decrease in the progression of vascular atherosclerosis and a decrease in the risk of developing cardiac complications due to atherosclerosis.

Contraindications to the use of alpha-glucosidase inhibitors:

Inflammatory bowel diseases;
Cirrhosis of the liver;
Intestinal ulcers;
Intestinal strictures;
Chronic renal failure;
Pregnancy and lactation.

Thiazolidinedione derivatives (glitazones)

Representatives of this group of tablets pioglitazone (Actos), rosiglitazone (Avandia), pioglar. The action of this drug group is due to an increase in the sensitivity of target tissues to the action of insulin, thereby increasing the utilization of glucose. Glitazones do not affect insulin synthesis by beta cells. The hypoglycemic effect of thiazolidinedione derivatives begins to appear after a month, and it may take up to three months to obtain the full effect.

According to research data, glitazones improve lipid metabolism and also reduce the level of certain factors that play a role in atherosclerotic vascular damage. Large-scale studies are currently underway to determine whether glitazones can be used as a means to prevent type 2 diabetes and reduce the incidence of cardiovascular complications.

However, thiazolidinedione derivatives also have side effects: increased body weight and a certain risk of heart failure.

Glinide derivatives

Representatives of this group are repaglinide (novonorm) And nateglinide (Starlix). These are short-acting medications that stimulate insulin secretion, which helps keep glucose levels under control after meals. In case of severe hyperglycemia on an empty stomach, glinides are ineffective.

The insulinotropic effect develops quite quickly when taking glinides. Thus, insulin production occurs twenty minutes after taking Novonorm tablets and five to seven minutes after taking Starlix.

Side effects include weight gain, as well as a decrease in the effectiveness of the drug with long-term use.

Contraindications include the following conditions:

Insulin-dependent diabetes;
Kidney, liver failure;
Pregnancy and lactation.

Incretins

This is a new class of hypoglycemic drugs, which includes derivatives of dipeptidyl peptidase-4 (DPP-4) inhibitors and derivatives of glucagon-like peptide-1 (GLP-1) agonists. Incretins are hormones that are released from the intestines when you eat. They stimulate insulin secretion and the main role in this process is played by glucose-dependent insulinotropic (GIP) and glucagon-like peptides (GLP-1). This happens in a healthy body. And in a patient with type 2 diabetes, the secretion of incretins decreases, and the secretion of insulin decreases accordingly.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are essentially activators of GLP-1 and GIP. Under the influence of DPP-4 inhibitors, the duration of action of incretins increases. A representative dipeptidyl peptidase-4 inhibitor is sitagliptin, which is marketed under the trade name Januvia.

Januvia stimulates insulin secretion and also suppresses the secretion of the hormone glucagon. This occurs only under conditions of hyperglycemia. At normal glucose concentrations, the above mechanisms are not activated, this helps to avoid hypoglycemia, which happens when treated with glucose-lowering drugs of other groups. Januvia is available in tablet form.

But derivatives of GLP-1 agonists (Victoza, Lyxumia) are available in the form of solutions for subcutaneous administration, which is of course less convenient than using tablets.

SGLT2 inhibitor derivatives

Sodium-glucose cotransporter type 2 (SGLT2) inhibitor derivatives are a newer group of hypoglycemic drugs. Its representatives dapagliflozin And canagliflozin were approved by the FDA in 2012 and 2013, respectively. The mechanism of action of these tablets is based on inhibition of the activity of SGLT2 (sodium-glucose cotransporter type 2).

SGLT2 is the main transport protein involved in the reabsorption (reabsorption) of glucose from the kidneys into the blood. SGLT2 inhibitor medications lower blood glucose concentrations by reducing its renal reabsorption. That is, the drugs stimulate the release of glucose in the urine.

Associated effects with the use of SGLT2 inhibitors are a decrease in blood pressure and body weight. Among the side effects of the drug, the development of hypoglycemia and genitourinary infections is possible.

Dapagliflozin and canagliflozin are contraindicated in insulin-dependent diabetes, ketoacidosis, renal failure, and pregnancy.

Important! The same medicine affects people differently. Sometimes it is not possible to achieve the desired effect during therapy with a single drug. In such cases, combined treatment with several oral hypoglycemic drugs is resorted to. This therapeutic regimen makes it possible to influence different parts of the disease, increase insulin secretion, and also reduce tissue insulin resistance.

Grigorova Valeria, medical observer

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Alpha glucosidase inhibitors

α-glucosidase inhibitors are a group of drugs that block the activity of special intestinal enzymes - α-glucosidases. Disaccharides and oligosaccharides are not absorbed in the intestine, but under the action of α-glucosidases they are broken down into monosaccharides that can be absorbed.

Currently, two drugs are used in clinical practice: acarbose and miglitol.

The mechanism of action of α-glucosidase inhibitors is primarily associated with their effect on enzymes located in the “brush border” of enterocytes. Acarbose and miglitol reversibly and competitively inhibit α-glucosidase, glucamylase, sucrase, dextrinase, maltase, and only to a small extent α-amylase (acarbose) and lactase (miglitol).

Due to the pharmacokinetic properties of these drugs, their action mainly occurs in the upper part of the small intestine. In the distal part of the small intestine, the ability to inhibit α-glucosidases is weakened, so undigested oligo- and disaccharides are still broken down into monosaccharides and absorbed into the enterocytes.

Thus, under the influence of α-glucosidase inhibitors, the fermentation processes of complex carbohydrates slow down, and, as a result, the rate of absorption of fermentation products (monosaccharides) decreases. Accordingly, there is no sharp rise in glycemic levels after eating.

Neither acarbose nor miglitol have an effect on the absorption of simple carbohydrates (glucose, fructose), therefore the antihyperglycemic effect of α-glucosidase inhibitors is manifested only with the predominant consumption of complex carbohydrates (products containing starch, dextrins, disaccharides).

α-glucosidase inhibitors act directly in the small intestine. It is not surprising that only 2% of the absorbed dose of acarbose is absorbed and enters the systemic circulation, and the bulk of the acarbose is eventually broken down by microorganisms inhabiting the small intestine.

Miglitol, on the contrary, is completely absorbed in the proximal small intestine. T1/2 of miglitol and acarbose from blood plasma is about 2 hours, elimination is carried out by the kidneys.

Medicines that interfere with the absorption of carbohydrates in the intestine are used to treat type 2 diabetes mellitus, mainly in combination with other oral hypoglycemic agents. This takes advantage of the ability of α-glucosidase inhibitors to effectively reduce postprandial blood glucose levels, and correction of fasting blood glucose levels is usually achieved using sulfonylureas or metformin. When taking α-glucosidase inhibitors, the pharmacokinetics of sulfonylurea derivatives and metformin do not change.

α-glucosidase inhibitors can also be combined with insulin therapy.

Side effects of α-glucosidase inhibitors cannot be considered dangerous, however, they often become the reason for drug withdrawal. As a result of the action of drugs, a significant amount of carbohydrates enters the large intestine. Here they undergo fermentation processes with the formation of large amounts of gases. As a result, patients often experience flatulence and diarrhea. The severity of side effects can be reduced if you start therapy with small doses and increase the dose gradually. Medicines should be taken without chewing, with a small amount of liquid, immediately before or during meals.

During therapy with α-glucosidase inhibitors, hypoglycemia does not develop, however, if hypoglycemia occurs for another reason (for example, due to an overdose of sulfonylurea derivatives), then drugs from this group can significantly slow down the absorption of carbohydrates taken orally to correct hypoglycemia. In other words, despite the intake of carbohydrates (sugar, flour products) orally, hypoglycemia may worsen. In such a situation, to correct hypoglycemia, the patient should use products containing simple glucose (sweet carbonated drinks) or tableted glucose.

In patients taking acarbose, especially at high doses, increases in alanine transaminase (ALT) and asparagine transaminase (AST) are sometimes detected, but it is not yet entirely clear why. In this regard, in the first year of taking α-glucosidase inhibitors, it is necessary to regularly (usually every 3 months) determine the activity of ALT and AST in the blood serum. If enzyme activity increases, it is necessary to reduce the dose of the drug. If there is a persistent increase in the activity of ALT and AST, the question of the advisability of further continuing to take α-glucosidase inhibitors should be decided.

Contraindications to the use of drugs that increase insulin secretion include:

Pregnancy.
Lactation.
Chronic bowel diseases.
Acute and chronic hepatitis and pancreatitis.
Age under 18 years.

During pregnancy and breastfeeding, the use of α-glucosidase inhibitors is not advisable.

The safety and effectiveness of the use of drugs in this group in children have not been determined.

The effectiveness of α-glucosidase inhibitors may be reduced when co-administered with drugs containing digestive enzymes.

Subgroup drugs excluded.

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Description

Hypoglycemic or antidiabetic drugs are medications that lower blood glucose levels and are used to treat diabetes mellitus.

Along with insulin, the preparations of which are suitable only for parenteral use, there are a number of synthetic compounds that have a hypoglycemic effect and are effective when taken orally. These drugs are mainly used for type 2 diabetes mellitus.

- Oral hypoglycemic (glycemic) agents can be classified as follows: sulfonylurea derivatives

- (glibenclamide, gliquidone, gliclazide, glimepiride, glipizide, chlorpropamide); meglitinides

- (nateglinide, repaglinide); biguanides

- (buformin, metformin, phenformin); thiazolidinediones

- (pioglitazone, rosiglitazone, ciglitazone, englitazone, troglitazone); alpha-glucosidase inhibitors

(acarbose, miglitol);

The hypoglycemic properties of sulfonylurea derivatives were discovered by chance. The ability of compounds of this group to have a hypoglycemic effect was discovered in the 50s, when a decrease in blood glucose levels was noted in patients receiving antibacterial sulfonamide drugs for the treatment of infectious diseases. In this regard, the search for sulfonamide derivatives with a pronounced hypoglycemic effect began and in the 50s. The synthesis of the first sulfonylurea derivatives was carried out, which could be used to treat diabetes mellitus. The first such drugs were carbutamide (Germany, 1955) and tolbutamide (USA, 1956). In the early 50s. these sulfonylurea derivatives have begun to be used in clinical practice. In the 60-70s. Second generation sulfonylurea drugs appeared. The first representative of the second generation sulfonylurea drugs, glibenclamide, began to be used for the treatment of diabetes mellitus in 1969, in 1970 glybornuride began to be used, and in 1972 glipizide. Gliclazide and gliquidone appeared almost simultaneously.

In 1997, repaglinide (a group of meglitinides) was approved for the treatment of diabetes mellitus.

The history of the use of biguanides dates back to the Middle Ages, when the plant was used to treat diabetes mellitus Galega officinalis(French lily). At the beginning of the 19th century, the alkaloid galegin (isoamylene guanidine) was isolated from this plant, but in its pure form it turned out to be very toxic. In 1918-1920 The first drugs were developed - guanidine derivatives - biguanides. Subsequently, due to the discovery of insulin, attempts to treat diabetes mellitus with biguanides faded into the background. Biguanides (phenformin, buformin, metformin) were introduced into clinical practice only in 1957-1958. following the first generation sulfonylurea derivatives. The first drug in this group was phenformin (due to a pronounced side effect - the development of lactic acidosis - it was withdrawn from use). Buformin, which has a relatively weak hypoglycemic effect and a potential risk of developing lactic acidosis, has also been discontinued. Currently, only metformin is used from the biguanide group.

Thiazolidinediones (glitazones) entered clinical practice in 1997. The first drug approved for use as a hypoglycemic agent was troglitazone, but in 2000 its use was prohibited due to high hepatotoxicity. To date, two drugs from this group are used - pioglitazone and rosiglitazone.

Action sulfonylurea derivatives associated mainly with stimulation of pancreatic beta cells, accompanied by mobilization and increased release of endogenous insulin. The main prerequisite for the manifestation of their effect is the presence of functionally active beta cells in the pancreas. On the beta cell membrane, sulfonylurea derivatives bind to specific receptors associated with ATP-dependent potassium channels. The sulfonylurea receptor gene has been cloned. The classical high-affinity sulfonylurea receptor (SUR-1) was found to be a protein with a molecular mass of 177 kDa. Unlike other sulfonylureas, glimepiride binds to another ATP-dependent potassium channel-coupled protein with a molecular weight of 65 kDa (SUR-X). In addition, the K + channel includes the intramembrane subunit Kir 6.2 (a protein with a molecular weight of 43 kDa), which is responsible for the transport of potassium ions. It is believed that as a result of this interaction, the potassium channels of the beta cells are “closed.” An increase in the concentration of K + ions inside the cell promotes membrane depolarization, the opening of voltage-dependent Ca 2+ channels, and an increase in the intracellular content of calcium ions. The result of this is the release of insulin stores from the beta cells.

With long-term treatment with sulfonylurea derivatives, their initial stimulating effect on insulin secretion disappears. It is believed that this is due to a decrease in the number of receptors on beta cells. After a break in treatment, the response of beta cells to drugs of this group is restored.

Some sulfonylureas also have extrapancreatic effects. Extrapancreatic effects are of little clinical significance; they include an increase in the sensitivity of insulin-dependent tissues to endogenous insulin and a decrease in glucose production in the liver. The mechanism for the development of these effects is due to the fact that these drugs (especially glimepiride) increase the number of insulin-sensitive receptors on target cells, improve insulin-receptor interaction, and restore post-receptor signal transduction.

In addition, there is evidence that lead sulfonylureas stimulate the release of somatostatin and thereby suppress glucagon secretion.

Sulfonylurea derivatives:

I generation: tolbutamide, carbutamide, tolazamide, acetohexamide, chlorpropamide.

II generation: glibenclamide, glisoxepide, glibornuril, gliquidone, gliclazide, glipizide.

III generation: glimepiride.

Currently, first generation sulfonylurea drugs are practically not used in Russia.

The main difference between the second generation drugs and the first generation sulfonylurea derivatives is their greater activity (50-100 times), which allows them to be used in lower doses and, accordingly, reduces the likelihood of side effects. Individual representatives of hypoglycemic sulfonylurea derivatives of the 1st and 2nd generation differ in activity and tolerability. Thus, the daily dose of first generation drugs - tolbutamide and chlorpropamide - is 2 and 0.75 g, respectively, and the second generation drugs - glibenclamide - 0.02 g; gliquidone - 0.06-0.12 g. Second generation drugs are usually better tolerated by patients.

Sulfonylurea drugs have different severity and duration of action, which determines the choice of drugs when prescribed. Glibenclamide has the most pronounced hypoglycemic effect of all sulfonylurea derivatives. It is used as a standard for assessing the hypoglycemic effect of newly synthesized drugs. The powerful hypoglycemic effect of glibenclamide is due to the fact that it has the greatest affinity for ATP-dependent potassium channels of pancreatic beta cells. Currently, glibenclamide is produced both in the form of a traditional dosage form and in the form of a micronized form - a form of glibenclamide crushed in a special way, providing an optimal pharmacokinetic and pharmacodynamic profile due to rapid and complete absorption (bioavailability - about 100%) and making it possible to use drugs in in smaller doses.

Gliclazide is the second most commonly prescribed oral hypoglycemic agent after glibenclamide. In addition to the fact that gliclazide has a hypoglycemic effect, it improves hematological parameters, rheological properties of blood, and has a positive effect on the hemostasis and microcirculation system; prevents the development of microvasculitis, incl.

damage to the retina of the eye; suppresses platelet aggregation, significantly increases the relative disaggregation index, increases heparin and fibrinolytic activity, increases heparin tolerance, and also exhibits antioxidant properties.

Glipizide, having a pronounced effect, poses minimal danger in terms of hypoglycemic reactions, since it does not accumulate and does not have active metabolites.

Oral antidiabetic drugs are the mainstay of drug therapy for type 2 (non-insulin-dependent) diabetes mellitus and are usually prescribed to patients over 35 years of age without ketoacidosis, nutritional deficiency, complications or comorbidities requiring immediate insulin therapy.

Sulfonylurea drugs are not recommended for patients whose daily insulin requirement exceeds 40 units with a proper diet. They are also not prescribed to patients with severe forms of diabetes mellitus (with severe beta-cell deficiency), with a history of ketosis or diabetic coma, with hyperglycemia above 13.9 mmol/l (250 mg%) on an empty stomach and high glucosuria during diet therapy.

Transferring patients with diabetes mellitus on insulin therapy to treatment with sulfonylurea drugs is possible if disturbances in carbohydrate metabolism are compensated for with insulin doses of less than 40 units/day. At doses of insulin up to 10 units/day, you can immediately switch to treatment with sulfonylurea derivatives.

Long-term use of sulfonylurea derivatives can cause the development of resistance, which can be overcome by combination therapy with insulin drugs. In type 1 diabetes mellitus, the combination of insulin preparations with sulfonylurea derivatives makes it possible to reduce the daily need for insulin and helps to improve the course of the disease, including slowing the progression of retinopathy, which is to a certain extent associated with the angioprotective activity of sulfonylurea derivatives (especially the second generation). However, there are indications of their possible atherogenic effect.

In addition to the fact that sulfonylureas are combined with insulin (this combination is considered appropriate if the patient's condition does not improve with more than 100 units of insulin per day), they are sometimes combined with biguanides and acarbose.

When using sulfonamide hypoglycemic drugs, it should be taken into account that antibacterial sulfonamides, indirect anticoagulants, butadione, salicylates, ethionamide, tetracyclines, chloramphenicol, cyclophosphamide inhibit their metabolism and increase their effectiveness (hypoglycemia may develop). When sulfonylurea derivatives are combined with thiazide diuretics (hydrochlorothiazide, etc.) and CCBs (nifedipine, diltiazem, etc.) in large doses, antagonism occurs - thiazides interfere with the effect of sulfonylurea derivatives due to the opening of potassium channels, and CCBs disrupt the flow of calcium ions into the beta cells of the pancreas glands.

Sulfonylureas enhance the effects and intolerance of alcohol, probably due to a delay in the oxidation of acetaldehyde. Antabuse-like reactions are possible.

All sulfonamide hypoglycemic drugs are recommended to be taken 1 hour before meals, which contributes to a more pronounced decrease in postprandial (after meals) glycemia. In case of severe dyspeptic symptoms, it is recommended to use these drugs after meals.

Undesirable effects of sulfonylurea derivatives, in addition to hypoglycemia, are dyspeptic disorders (including nausea, vomiting, diarrhea), cholestatic jaundice, weight gain, reversible leukopenia, thrombocytopenia, agranulocytosis, aplastic and hemolytic anemia, allergic reactions (including . itching, erythema, dermatitis).

The use of sulfonylureas during pregnancy is not recommended, because most of them are class C according to the FDA (Food and Drug Administration), and insulin therapy is prescribed instead.

Elderly patients are not recommended to use long-acting drugs (glibenclamide) due to the increased risk of hypoglycemia. At this age, it is preferable to use short-acting derivatives - gliclazide, gliquidone.

Meglitinides - prandial regulators (repaglinide, nateglinide).

Repaglinide is a derivative of benzoic acid. Despite the difference in chemical structure from sulfonylurea derivatives, it also blocks ATP-dependent potassium channels in the membranes of functionally active beta cells of the pancreatic islet apparatus, causes their depolarization and the opening of calcium channels, thereby inducing insulin incretion. The insulinotropic response to food intake develops within 30 minutes after administration and is accompanied by a decrease in blood glucose levels during the meal period (insulin concentrations do not increase between meals). As with sulfonylureas, the main side effect is hypoglycemia. Repaglinide should be prescribed with caution to patients with hepatic and/or renal insufficiency.

Biguanides , which began to be used to treat type 2 diabetes in the 70s, do not stimulate the secretion of insulin by beta cells of the pancreas. Their action is mainly determined by inhibition of gluconeogenesis in the liver (including glycogenolysis) and increased utilization of glucose by peripheral tissues. They also inhibit the inactivation of insulin and improve its binding to insulin receptors (this increases the absorption of glucose and its metabolism).

Biguanides (unlike sulfonylurea derivatives) do not reduce blood glucose levels in healthy people and in patients with type 2 diabetes after an overnight fast, but significantly limit its increase after a meal without causing hypoglycemia.

Hypoglycemic biguanides - metformin and others - are also used for type 2 diabetes mellitus. In addition to their hypoglycemic effect, biguanides have a positive effect on lipid metabolism with long-term use. Drugs in this group inhibit lipogenesis (the process by which glucose and other substances are converted into fatty acids in the body), activate lipolysis (the process of breaking down lipids, especially triglycerides contained in fat, into their constituent fatty acids under the action of the lipase enzyme), reduce appetite, and promote reduction in body weight. In some cases, their use is accompanied by a decrease in the content of triglycerides, cholesterol and LDL (determined on an empty stomach) in the blood serum. In type 2 diabetes mellitus, carbohydrate metabolism disorders are combined with pronounced changes in lipid metabolism. Thus, 85-90% of patients with type 2 diabetes mellitus have increased body weight. Therefore, when type 2 diabetes mellitus is combined with excess body weight, drugs that normalize lipid metabolism are indicated.

The indication for the prescription of biguanides is type 2 diabetes mellitus (especially in cases accompanied by obesity) with the ineffectiveness of diet therapy, as well as with the ineffectiveness of sulfonylurea drugs.

In the absence of insulin, the effect of biguanides does not occur.

Biguanides can be used in combination with insulin in the presence of insulin resistance. The combination of these drugs with sulfonamide derivatives is indicated in cases where the latter do not provide complete correction of metabolic disorders. Biguanides can cause the development of lactic acidosis (lactic acidosis), which limits the use of drugs in this group.

Biguanides are contraindicated in the presence of acidosis and a tendency to it (they provoke and enhance the accumulation of lactate), in conditions accompanied by hypoxia (including cardiac and respiratory failure, acute phase of myocardial infarction, acute cerebral circulatory failure, anemia), etc.

Side effects of biguanides are observed more often than with sulfonylurea derivatives (20% versus 4%), primarily these are adverse reactions from the gastrointestinal tract: metallic taste in the mouth, dyspeptic symptoms, etc. Unlike sulfonylurea derivatives, hypoglycemia when using biguanides (for example, metformin ) occurs very rarely.

Lactic acidosis, which sometimes appears when taking metformin, is considered a serious complication, so metformin should not be prescribed for renal failure and conditions that predispose to its development - impaired renal and/or liver function, heart failure, pulmonary pathology.

Biguanides should not be prescribed simultaneously with cimetidine, since they compete with each other in the process of tubular secretion in the kidneys, which can lead to the accumulation of biguanides, in addition, cimetidine reduces the biotransformation of biguanides in the liver.

The combination of glibenclamide (a second-generation sulfonylurea derivative) and metformin (a biguanide) optimally combines their properties, making it possible to achieve the required hypoglycemic effect with a lower dose of each drug and thereby reduce the risk of side effects.

Since 1997, clinical practice has included thiazolidinediones (glitazones), The chemical structure of which is based on the thiazolidine ring. This new group of antidiabetic agents includes pioglitazone and rosiglitazone. Drugs in this group increase the sensitivity of target tissues (muscles, adipose tissue, liver) to insulin and reduce lipid synthesis in muscle and fat cells. Thiazolidinediones are selective agonists of nuclear receptors PPARγ (peroxisome proliferator-activated receptor-gamma). In humans, these receptors are located in the main “target tissues” for insulin action: adipose tissue, skeletal muscle and liver. Nuclear receptors PPARγ regulate the transcription of insulin-responsive genes involved in the control of glucose production, transport and utilization. In addition, PPARγ-responsive genes are involved in fatty acid metabolism.

In order for thiazolidinediones to have their effect, insulin must be present. These drugs reduce insulin resistance of peripheral tissues and the liver, increase the consumption of insulin-dependent glucose and reduce the release of glucose from the liver; reduce average triglyceride levels, increase HDL and cholesterol concentrations; prevent hyperglycemia on an empty stomach and after meals, as well as glycosylation of hemoglobin.

Alpha-glucosidase inhibitors (acarbose, miglitol) inhibit the breakdown of poly- and oligosaccharides, reducing the formation and absorption of glucose in the intestine and thereby preventing the development of postprandial hyperglycemia. Carbohydrates taken with food enter unchanged into the lower parts of the small and large intestines, while the absorption of monosaccharides is prolonged up to 3-4 hours. Unlike sulfonamide hypoglycemic agents, they do not increase the release of insulin and, therefore, do not cause hypoglycemia.

It has been shown that long-term therapy with acarbose is accompanied by a significant reduction in the risk of developing atherosclerotic cardiac complications. Alpha-glucosidase inhibitors are used as monotherapy or in combination with other oral hypoglycemic agents. The initial dose is 25-50 mg immediately before or during meals, and can subsequently be gradually increased (maximum daily dose 600 mg).

Indications for the use of alpha-glucosidase inhibitors are type 2 diabetes mellitus when diet therapy is ineffective (the course of which should be at least 6 months), as well as type 1 diabetes mellitus (as part of combination therapy).

Drugs in this group can cause dyspeptic symptoms due to impaired digestion and absorption of carbohydrates, which are metabolized in the large intestine with the formation of fatty acids, carbon dioxide and hydrogen. Therefore, when prescribing alpha-glucosidase inhibitors, strict adherence to a diet with a limited content of complex carbohydrates, incl.

sucrose.

Acarbose can be combined with other antidiabetic agents. Neomycin and cholestyramine enhance the effect of acarbose, and the frequency and severity of side effects from the gastrointestinal tract increase. When used together with antacids, adsorbents and enzymes that improve the digestion process, the effectiveness of acarbose is reduced. Currently, a fundamentally new class of hypoglycemic drugs has emerged -. incretin mimetics

Incretins are hormones that are secreted by certain types of cells in the small intestine in response to food intake and stimulate the secretion of insulin. Two hormones have been isolated: glucagon-like polypeptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

Incretin mimetics include 2 groups of drugs:

Substances that prolong the action of endogenous GLP-1 due to the blockade of dipeptidyl peptidase-4 (DPP-4), an enzyme that destroys GLP-1, are DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin).

Thus, the group of hypoglycemic drugs includes a number of effective drugs. They have different mechanisms of action and differ in pharmacokinetic and pharmacodynamic parameters. Knowledge of these features allows the doctor to make the most individual and correct choice of therapy.

Drugs

Drugs - 5165 ; Trade names - 163 ; Active ingredients - 36

Active substance	Trade names
Information is absent














St. John's wort herb + Chamomile flowers + Common bean leaf fruit + Horsetail herb + Blueberry shoots + Rose hips fruits + Eleutherococcus senticosus rhizomes and roots (Herba Hyperici + Flores Chamomillae + Fructus Phaseoli + Herba Equiseti + Cormus Myrtilli + Fructus Rosae + Rhizomata et radices Eleutherococci)

As a result, after a meal, postprandial glycemia decreases and, secondary to it, postprandial hyperinsulinemia. Since not only hyperglycemia, but also hyperinsulinemia reduces the risk of cardiovascular complications of T2DM, this latter effect is believed to be an additional advantage of treatment with alpha-glucosidase inhibitors compared with insulin secretagogues.

Mechanism of action. Drugs in this group reversibly bind alpha-glucosidase enzymes (sucrose, maltose, isomaltose and glucoamylase) in the lumen of the small intestine. As a result, the breakdown of disaccharides and oligosaccharides (for example, sugar and starch) into glucose and fructose is blocked. Competitive (relative to food carbohydrates) and reversible binding of alpha-glucosidases completely suppresses the absorption of carbohydrates in the proximal intestine, which leads to a decrease in the peak of postprandial glycemia after ingestion of complex carbohydrates. Currently, two drugs of this group are produced - acarbose and miglitol, the action of which is slightly different. Miglitol does not suppress lactose, but acarbose does suppress it, but so slightly (-10%) that this does not affect the action of lactose in any way. Acarbose also inhibits pancreatic amylase, but miglitol does not. But the clinical effects of these drugs are the same. Since miglitol, unlike acarbose, is absorbed, its systemic effects on metabolic processes have been studied. It turned out that it suppresses glycogenolysis in liver tissue in vitro. However, the manufacturers of miglitol have not detected any systemic action in the body, despite absorption.
Acarbose reduces the risk of cardiovascular complications, and when prescribed to patients with early disorders of carbohydrate metabolism, it can normalize it and reduce the risk of developing overt diabetes mellitus. The mechanism of this action of acarbose is still unclear, but by studying the kinetics of glucose in an intravenous glucose tolerance test, we were able to show that in early disorders of carbohydrate metabolism (IGT, IGN), it does not affect the production of glucose by the liver and the elimination of glucose in persons in whom treatment acarbose led to the normalization of previously impaired carbohydrate metabolism (NGN or IGT). That is, Acarbose eliminates early metabolic disorders without interfering with the intimate processes of the pathogenesis of T2DM, which is probably natural, given the “extraendocrine” mechanism of its action.

Pharmacokinetics. After administration, acarbose is practically not absorbed in the intestine - bioavailability is 1-2%, and the peak concentration in the blood is observed within 1 hour, from where it is excreted unchanged by the kidneys. Metabolism of acarbose occurs exclusively in the intestine. Under the influence of natural intestinal flora and digestive enzymes, at least 13 metabolites are formed from acarbose, the bioavailability of which is already -34%, and they are absorbed 14-24 hours after formation in the intestine. Only one of the alpha-glucosidase metabolites retains its inhibitory effect on alpha-glucosidases.
The peak concentration of miglitol after administration occurs in the blood within 3 hours, and the half-life is 2-3 hours. Its absorption depends on the dose: the higher, the less and is -95%. But since the point of its action is the villi of the small intestine, the absorption of miglitol does not in any way affect the glucose-lowering effectiveness of the drug. Miglitol is excreted unchanged from the blood by the kidneys, and the drug remaining in the intestines is excreted in the feces, also unchanged. Miglitol is not metabolized in the body.

Interaction with other drugs. When combined with alpha-glucosidase inhibitors and insulin or other antidiabetic drugs, the hypoglycemic effect of the latter may be enhanced, which may cause hypoglycemia. In these cases, the dose of any glucose-lowering drug in the combination should be reduced. Any drugs that increase blood glucose, such as thiazide diuretics, corticosteroids, oral contraceptives, and estrogens, niacin, phenothiazides, thyroid hormones, and calcium channel blockers, may reduce the effectiveness of alpha-glucosidase inhibitors. Although miglitol reduces the degree of absorption and the peak concentration of glibenclamide and metformin, this does not manifest itself clinically. Acarbose reduces the bioavailability of metformin, but this does not affect its effectiveness. Acarbose does not interact with digoxin, nifedipine, propranolol or ranitidine. Since acarbose in very large doses causes an increase in liver enzymes, it is undesirable to combine it with paracetamol (a known liver toxin), especially in people who abuse alcohol. Miglitol reduces the level of digoxin in the blood, as well as the bioavailability of propranolol and ranitidine, but does not interact with nifedipine, antacids or warfarin. Activated charcoal and digestive enzymes such as amylase and pancreatin may interfere with the action of alpha-glucosidase inhibitors locally in the intestine.

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Drugs, doses and treatment regimens. It should be noted that in many patients, in order to avoid side effects, treatment with an alpha-glucosidase inhibitor should be started with one tablet per day at a dose of 25 mg. The drug should be taken at the beginning of a meal, with the largest meal, which must contain complex carbohydrates (alpha-glucosidase inhibitors act only in the presence of polysaccharides in food). The dose is then increased by 25 mg/day and no more than once a week until it is prescribed with all main meals. The maximum dose (300 mg) may be prescribed, but it should be borne in mind that increasing the dose above the average usually gives a slight glucose-lowering increase, and side effects increase proportionally and significantly with increasing dose. Typically a dose of 50 mg 3 times daily produces maximum effect.

Indications. Acarbose, like miglitol, can be prescribed to patients with T2DM as initial monotherapy or in combination with other hypoglycemic drugs - metformin, sulfonamides or insulin. Several large studies with acarbose, including the large post-marketing PROTECT (Precose Resolution of Optimal Titration to Enchance Current Therapies) study, which involved more than 6,000 diabetic patients, showed that treatment with Acarbose reduced HbA1c levels by 0.6-1. 1%, postprandial glycemia - by 2.2-2.8 mmol/l, and fasting glycemia - by 1.4-1.7 mmol/l.
Small and short-term studies of the effectiveness of miglitol found a decrease in HbA1c by 0.4-1.2%, postprandial glycemia by 1.1-3.3 mmol/l and a slight decrease in postprandial hyperinsulinemia.
The clinical effectiveness of both drugs is believed to be comparable, although no special comparative studies have been conducted, which does not allow us to objectively highlight any advantages of each of them. Age does not affect the effectiveness of treatment. Despite suppressing carbohydrate absorption, the drugs do not cause weight loss.
In Russia, only acarbose is used, although not very often. Reasons for this may be the need to titrate the dose of alpha-glucosidase inhibitors over 10-12 weeks in order to exclude the possibility of side effects, as well as the more noticeable glucose-lowering effect of other antidiabetic drugs.

Contraindications and restrictions. Although alpha-glucosidase inhibitors themselves do not cause hypoglycemia, they can enhance the hypoglycemic effect of sulfonamides or insulin if combined with them. In the case of hypoglycemia that develops while taking alpha-glucosidase inhibitors, it should be eliminated exclusively by taking monosaccharides, glucose in particular. Taking complex carbohydrates (sandwich, etc.) in this case is less effective, because alpha-glucosidase inhibitors reduce the degree of digestion of complex carbohydrates in the gastrointestinal tract. Since alpha-glucosidase inhibitors are excreted by the kidneys, especially miglitol, they are contraindicated in patients with creatinine clearance levels<25 мл/мин. Больным с нарушением функции печени не нужно модифицировать дозу ингибиторов альфа-глюкозидазы, так как они не метаболизируются в печени. Вместе с тем больным с циррозом печени акарбозу назначать не рекомендуется из-за частых желудочно-кишечных побочных действий (вздутие живота и т.п.).
It is not recommended to prescribe these drugs to pregnant women, since their safety in pregnant women has not been studied, and since they are excreted in small quantities in milk, they are not prescribed to breastfeeding women.
Acarbose and miglitol are contraindicated in case of hypersensitivity to them, diabetic ketoacidosis, and plasma creatinine<2,0 мг% (176 ммоль/л) и следующих болезнях органов пищеварения:

inflammatory bowel diseases;
ulcerative colitis;
partial intestinal obstruction;
chronic intestinal diseases, which are accompanied by significant disruption of the processes of digestion and/or absorption, or in conditions that are aggravated by increased formation of gases in the intestines;
liver cirrhosis.

Side effects of alpha-glucosidase inhibitors are associated with the main mechanism of their action - the slowing down of carbohydrate absorption under their influence contributes to their accumulation in the distal parts of the intestine, in particular the large intestine, the flora of which begins to produce excess amounts of gas. As a result, 1/3 - 2/3 of patients experience most of the side symptoms of treatment with alpha-glucosidase inhibitors: flatulence, a feeling of abdominal distension, pain and diarrhea. However, the intensity of these symptoms with continued treatment usually decreases due to the redistribution of digestive enzymes in the intestine, which usually takes several weeks.
In some patients, during treatment with acarbose at a high dose, an increase in the level of liver enzymes was observed, which returned to normal after discontinuation of the drug. It is therefore recommended to monitor liver enzymes every three months during the first year of treatment with alpha-glucosidase inhibitors and reduce the dose or discontinue them if liver enzyme levels increase.

The antidiabetic effect of drugs in this group is reduced to slowing the absorption of complex carbohydrates (including starch and sugar) in the small intestine. Typically, in order to cross the intestinal barrier, polysaccharides need to be broken down into simple sugars (monosaccharides), which can be absorbed through the intestinal wall. Thus, α-glucosidase inhibitors make it difficult for carbohydrates to enter the bloodstream, thereby affecting blood sugar levels after meals.

This class of drugs (α-glucosidase inhibitors, A10BF) includes:

Among other things, studies have shown that the culinary Maitake mushroom (Grifola frondosa) has a hypoglycemic effect. The reason why Maitake lowers blood sugar levels is because it naturally contains an α-glucosidase inhibitor.

The medicinal herb Tribulus terrestris has also been shown to lower blood sugar levels in human and animal studies. The reason is the content of steroidal saponins, which have an inhibitory effect on alpha-glucosidases.

Glucosidase inhibitors

Currently, two drugs are used in clinical practice: acarbose and miglitol.

Miglitol, on the contrary, is completely absorbed in the proximal small intestine. T1/2 of miglitol and acarbose from blood plasma is about 2 hours, elimination is carried out by the kidneys.

α-glucosidase inhibitors can also be combined with insulin therapy.

Contraindications to the use of drugs that increase insulin secretion include:

Pregnancy.
Lactation.
Chronic bowel diseases.
Acute and chronic hepatitis and pancreatitis.
Age under 18 years.

During pregnancy and breastfeeding, the use of α-glucosidase inhibitors is not advisable.

The safety and effectiveness of the use of drugs in this group in children have not been determined.

The effectiveness of α-glucosidase inhibitors may be reduced when co-administered with drugs containing digestive enzymes.

Alpha glucosidase inhibitors - ATC classification of drugs

This section of the site contains information about drugs from the group - A10BF Alpha Glucosidase Inhibitors. Each drug is described in detail by specialists of the EUROLAB portal.

The Anatomical Therapeutic Chemical Classification (ATC) is an international drug classification system. The Latin name is Anatomical Therapeutic Chemical (ATC). Based on this system, all drugs are divided into groups according to their main therapeutic use. The ATC classification has a clear, hierarchical structure, which makes it easier to find the right drugs.

Each medicine has its own pharmacological action. Correctly identifying the right medications is a fundamental step for successfully treating diseases. In order to avoid undesirable consequences, before using certain medications, consult your doctor and read the instructions for use. Pay special attention to interactions with other medications, as well as conditions of use during pregnancy.

ATX A10BF Alpha glucosidase inhibitors:

Medicines group: Alpha glucosidase inhibitors

Glucobay (Oral tablets)
Diastabol (Oral tablets)

If you are interested in any other medicines and preparations, their descriptions and instructions for use, synonyms and analogues, information about the composition and form of release, indications for use and side effects, methods of use, dosages and contraindications, notes on the treatment of children with medicines, newborns and pregnant women, prices and reviews of medications, or you have any other questions and suggestions - write to us, we will definitely try to help you.

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ATC (ATS) - classification of drugs and medical products on the EUROLAB portal.

Alpha-glucosidase inhibitors

In Russia, the only drug of this class that is currently registered is acarbose (trade name Glucobay).

Mechanism of action

pros

Acarbose does not cause an increase in blood insulin levels (therefore, there is no risk of hypoglycemia).
Due to the fact that acarbose interferes with the absorption of carbohydrates, body weight decreases to one degree or another (as the calorie content of food decreases).
According to studies, long-term therapy with acarbose is accompanied by a significant reduction in the progression of vascular atherosclerosis.
Acarbose is not absorbed and therefore has no systemic effects.

Minuses

Carbohydrates that are not subject to enzymatic processing cause fermentation in the large intestine, which can be accompanied by flatulence and diarrhea. But this is not a side effect, it is the result of the action of the drug itself against the background of a diet disorder.
Acarbose has less hypoglycemic activity than metformin or sulfonylurea derivatives and reduces HbA 1C by 0.5–0.8%

Indications

Diabetes mellitus type 1 (as part of combination therapy). Acarbose is the only oral antidiabetic drug that can be used for type 1 diabetes.
Diabetes mellitus type 2.
Prevention of type 2 diabetes mellitus. Acarbose is the drug of choice for individuals with prediabetes, which is accompanied by postprandial hyperglycemia at normal fasting levels.

Contraindications and side effects

Side effects are rare: increased levels of transaminases (ALT and AST), intestinal obstruction, jaundice. Allergic reactions: skin rash (including urticaria), skin hyperemia.

Directions for use and doses

Acarbose is taken immediately before (or during) meals.

Treatment with acarbose should be carried out under the control of the level of glycosylated hemoglobin and transaminases in the first year of treatment - once every 3 months, then periodically.

Precautionary measures

When used together with antacids, sorbents and enzymes that improve the digestion process, the effectiveness of acarbose is significantly reduced.

File contents Oral hypoglycemic therapy

Alpha-glucosidase inhibitors - acarbose (Glucobay).

Oral hypoglycemic therapy

2. Acarbose (Glucobay)

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Alpha glucosidase inhibitors, which reduce carbohydrate absorption

Mechanism of action. Drugs in this group reversibly bind alpha-glucosidase enzymes (sucrose, maltose, isomaltose and glucoamylase) in the lumen of the small intestine. As a result, the breakdown of disaccharides and oligosaccharides (for example, sugar and starch) into glucose and fructose is blocked. Competitive (relative to food carbohydrates) and reversible binding of alpha-glucosidases completely suppresses the absorption of carbohydrates in the proximal intestine, which leads to a decrease in the peak of postprandial glycemia after ingestion of complex carbohydrates. Currently, two drugs of this group are produced - acarbose and miglitol, the action of which is slightly different. Miglitol does not suppress lactose, but acarbose does suppress it, but so slightly (-10%) that this does not affect the action of lactose in any way. Acarbose also inhibits pancreatic amylase, but miglitol does not. But the clinical effects of these drugs are the same. Since miglitol, unlike acarbose, is absorbed, its systemic effects on metabolic processes have been studied. It turned out that it suppresses glycogenolysis in liver tissue in vitro. However, the manufacturers of miglitol have not detected any systemic action in the body, despite absorption.

Acarbose reduces the risk of cardiovascular complications, and when prescribed to patients with early disorders of carbohydrate metabolism, it can normalize it and reduce the risk of developing overt diabetes mellitus. The mechanism of this action of acarbose is still unclear, but by studying the kinetics of glucose in an intravenous glucose tolerance test, we were able to show that in early disorders of carbohydrate metabolism (IGT, IGN), it does not affect the production of glucose by the liver and the elimination of glucose in persons in whom treatment acarbose led to the normalization of previously impaired carbohydrate metabolism (NGN or IGT). That is, Acarbose eliminates early metabolic disorders without interfering with the intimate processes of the pathogenesis of T2DM, which is probably natural, given the “extraendocrine” mechanism of its action.

Pharmacokinetics. After administration, acarbose is practically not absorbed in the intestine - bioavailability is 1-2%, and the peak concentration in the blood is observed within 1 hour, from where it is excreted unchanged by the kidneys. Metabolism of acarbose occurs exclusively in the intestine. Under the influence of natural intestinal flora and digestive enzymes, at least 13 metabolites are formed from acarbose, the bioavailability of which is already -34%, and they are absorbed 14-24 hours after formation in the intestine. Only one of the alpha-glucosidase metabolites retains its inhibitory effect on alpha-glucosidases.

The peak concentration of miglitol after administration occurs in the blood within 3 hours, and the half-life is 2-3 hours. Its absorption depends on the dose: the higher, the less and is -95%. But since the point of its action is the villi of the small intestine, the absorption of miglitol does not in any way affect the glucose-lowering effectiveness of the drug. Miglitol is excreted unchanged from the blood by the kidneys, and the drug remaining in the intestines is excreted in the feces, also unchanged. Miglitol is not metabolized in the body.

Interaction with other drugs. When combined with alpha-glucosidase inhibitors and insulin or other antidiabetic drugs, the hypoglycemic effect of the latter may be enhanced, which may cause hypoglycemia. In these cases, the dose of any glucose-lowering drug in the combination should be reduced. Any drugs that increase blood glucose, such as thiazide diuretics, corticosteroids, oral contraceptives, and estrogens, niacin, phenothiazides, thyroid hormones, and calcium channel blockers, may reduce the effectiveness of alpha-glucosidase inhibitors. Although miglitol reduces the degree of absorption and the peak concentration of glibenclamide and metformin, this does not manifest itself clinically. Acarbose reduces the bioavailability of metformin, but this does not affect its effectiveness. Acarbose does not interact with digoxin, nifedipine, propranolol or ranitidine. Since acarbose in very large doses causes an increase in liver enzymes, it is undesirable to combine it with paracetamol (a known liver toxin), especially in people who abuse alcohol. Miglitol reduces the level of digoxin in the blood, as well as the bioavailability of propranolol and ranitidine, but does not interact with nifedipine, antacids or warfarin. Activated charcoal and digestive enzymes such as amylase and pancreatin may interfere with the action of alpha-glucosidase inhibitors locally in the intestine.

Indications. Acarbose, like miglitol, can be prescribed to patients with T2DM as initial monotherapy or in combination with other hypoglycemic drugs - metformin, sulfonamides or insulin. Several large studies with acarbose, including the large post-marketing PROTECT (Precose Resolution of Optimal Titration to Enchance Current Therapies) study, which involved more than 6,000 diabetic patients, showed that treatment with Acarbose reduced HbA1c levels by 0.6-1. 1%, postprandial glycemia - by 2.2-2.8 mmol/l, and fasting glycemia - by 1.4-1.7 mmol/l.

Small and short-term studies of the effectiveness of miglitol found a decrease in HbA1c by 0.4-1.2%, postprandial glycemia by 1.1-3.3 mmol/l and a slight decrease in postprandial hyperinsulinemia.

In Russia, only acarbose is used, although not very often. Reasons for this may be the need to titrate the dose of alpha-glucosidase inhibitors over 10-12 weeks in order to exclude the possibility of side effects, as well as the more noticeable glucose-lowering effect of other antidiabetic drugs.

Contraindications and restrictions. Although alpha-glucosidase inhibitors themselves do not cause hypoglycemia, they can enhance the hypoglycemic effect of sulfonamides or insulin if combined with them. In the case of hypoglycemia that develops while taking alpha-glucosidase inhibitors, it should be eliminated exclusively by taking monosaccharides, glucose in particular. Taking complex carbohydrates (sandwich, etc.) in this case is less effective, because alpha-glucosidase inhibitors reduce the degree of digestion of complex carbohydrates in the gastrointestinal tract. Since alpha-glucosidase inhibitors are excreted by the kidneys, especially miglitol, they are contraindicated in patients with creatinine clearance levels<25 мл/мин. Больным с нарушением функции печени не нужно модифицировать дозу ингибиторов альфа-глюкозидазы, так как они не метаболизируются в печени. Вместе с тем больным с циррозом печени акарбозу назначать не рекомендуется из-за частых желудочно-кишечных побочных действий (вздутие живота и т.п.).

It is not recommended to prescribe these drugs to pregnant women, since their safety in pregnant women has not been studied, and since they are excreted in small quantities in milk, they are not prescribed to breastfeeding women.

Acarbose and miglitol are contraindicated in case of hypersensitivity to them, diabetic ketoacidosis, and plasma creatinine<2,0 мг% (176 ммоль/л) и следующих болезнях органов пищеварения:

inflammatory bowel diseases;
ulcerative colitis;
partial intestinal obstruction;
chronic intestinal diseases, which are accompanied by significant disruption of the processes of digestion and/or absorption, or in conditions that are aggravated by increased formation of gases in the intestines;
liver cirrhosis.

In some patients, during treatment with acarbose at a high dose, an increase in the level of liver enzymes was observed, which returned to normal after discontinuation of the drug. It is therefore recommended to monitor liver enzymes every three months during the first year of treatment with alpha-glucosidase inhibitors and reduce the dose or discontinue them if liver enzyme levels increase.

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3. Alpha-glucosidase inhibitors (Acarbose)

Drugs in this group reduce the absorption of carbohydrates from the intestine, inhibiting the activity of enzymes involved in the digestion of carbohydrates. Acarbose reversibly inhibits intestinal membrane-bound alpha-glucosidase and pancreatic alpha-amylase. In the lumen of the small intestine, alpha-amylase hydrolyzes polymeric sugars to oligosaccharides, and intestinal alpha-glucosidase hydrolyzes oligo-, di- and trisaccharides to glucose and other monosaccharides. Inactivation of these enzymes leads to a decrease in the formation of glucose in the intestine and, consequently, its absorption, that is, post-meal hyperglycemia is reduced, and excessive release of insulin in the second delayed phase of secretion is prevented.

After 3-6 months of treatment with acarbose, normalization of lipid metabolism is observed - the content of cholesterol and triglycerides decreases, and the content of “protective” high-density lipoproteins in the blood increases.

The drug increases the secretion of glucagon-like peptide I, which is an endogenous stimulator of the first phase of insulin secretion in response to increased blood glucose.

Thus, acarbose (glucobay) restores insulin secretion by the pancreas in the first phase and prevents the development of hyperinsulinemia in the second.

Only 35% of the administered dose is absorbed from the intestine, and only 2% in the active form. The half-life is 2 hours. The absorbed part of acarbose is excreted by the kidneys. In case of renal failure and in the elderly, the elimination of the drug slows down significantly, but this is of no practical importance, since acarbose, due to its low bioavailability, does not have a systemic effect. The hypoglycemic effect of the drug develops in the gastrointestinal tract, where its biotransformation occurs.

Indications and dosage regimen

Type II diabetes mellitus: mono- or combination therapy.

As monotherapy, Acarbose (Glucobay) is prescribed when diet therapy is ineffective. Acbose is also used in combination with sulfonylureas.

Take 25 mg of acarbose with the first sip of food 3 times a day. The dose of Domg is increased 3 times a day at 4-8 week intervals and is based on two criteria - the level of glucose in the blood 1 hour after meals and individual tolerance.

Hypersensitivity, diabetic ketoacidosis, acute and chronic intestinal diseases, pregnancy and lactation. Relatively contraindicated in type 1 diabetes, chronic renal failure, and in children under 18 years of age.

Dyspeptic symptoms (abdominal pain, flatulence, diarrhea), increased transaminase levels, jaundice. Decrease in hematocrit level (without changing hemoglobin concentration). Decrease in the concentration of calcium, vitamin B 6 in PC.

Interaction with other drugs

The effect is reduced by activated carbon and other adsorbents, digestive enzyme preparations containing pancreatin or amylase. Thiazide diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic acid, sipatomimetics, calcium antagonists, isoniazid weaken the effect. Sulfonylurea derivatives increase the effect.

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Oral hypoglycemic drugs: list, principle of their action

Types of oral glucose-lowering medications

There are many hypoglycemic drugs available, they differ from each other in their origin and chemical formula. The following groups of oral hypoglycemic agents are distinguished:

sulfonylurea derivatives;
glinides;
biguanides;
thiazolidinediones;
α-glucosidase inhibitors;
incretins.

In addition, a new group of hypoglycemic drugs has recently been synthesized - derivatives of sodium-glucose cotransporter type 2 (SGLT2) inhibitors.

Biguanide derivatives

Contraindications to the use of biguanides:

If a woman taking metformin becomes pregnant, she should stop using this medication. The use of metformin will be possible only after stopping breastfeeding.

Sulfonylurea derivatives

Very often, in the treatment of type 2 diabetes, they resort to the use of sulfonylurea derivatives. There are three generations of sulfonylurea drugs:

First generation: tolbutamide, tolazamide, chlorpropamide.
Second generation: glibenclamide, glisoxepide, gliquidone, glipizide.
Third generation: glimepiride.

Sulfonylurea derivatives stimulate insulin secretion and release from beta cells, and also restore the sensitivity of these cells to glycemia.

Not effective if the patient has significant loss of pancreatic beta cells;
In some patients, for unknown reasons, it does not have an antidiabetic effect;
Effective only if you follow a diet;
Must be taken half an hour before meals.

The main contraindications to the use of sulfonylurea drugs are type 1 diabetes mellitus, ketoacidosis, pregnancy and lactation, and major operations.

Alpha-glucosidase inhibitors

Contraindications to the use of alpha-glucosidase inhibitors:

Inflammatory bowel diseases;
Cirrhosis of the liver;
Intestinal ulcers;
Intestinal strictures;
Chronic renal failure;
Pregnancy and lactation.

Thiazolidinedione derivatives (glitazones)

However, thiazolidinedione derivatives also have side effects: increased body weight and a certain risk of heart failure.

Glinide derivatives

The insulinotropic effect develops quite quickly when taking glinides. Thus, insulin production occurs twenty minutes after taking Novonorm tablets and five to seven minutes after taking Starlix.

Side effects include weight gain, as well as a decrease in the effectiveness of the drug with long-term use.

Contraindications include the following conditions:

Insulin-dependent diabetes;
Kidney, liver failure;
Pregnancy and lactation.

Incretins

But derivatives of GLP-1 agonists (Victoza, Lyxumia) are available in the form of solutions for subcutaneous administration, which is of course less convenient than using tablets.

SGLT2 inhibitor derivatives

Dapagliflozin and canagliflozin are contraindicated in insulin-dependent diabetes, ketoacidosis, renal failure, and pregnancy.

Grigorova Valeria, medical observer

Glucosidase inhibitor. Oral hypoglycemic drugs: list, principle of their action

pros

Minuses

Indications

Contraindications and side effects

Directions for use and doses

Precautionary measures

File contents Oral hypoglycemic therapy

Alpha glucosidase inhibitors

GLUCOBAY

DIASTABOL

Oral hypoglycemic drugs: list, principle of their action

Types of oral glucose-lowering medications

Biguanide derivatives

Sulfonylurea derivatives

Alpha-glucosidase inhibitors

Thiazolidinedione derivatives (glitazones)

Glinide derivatives

Incretins

SGLT2 inhibitor derivatives

Alpha glucosidase inhibitors

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Drugs

Glucosidase inhibitors

Alpha glucosidase inhibitors - ATC classification of drugs

ATX A10BF Alpha glucosidase inhibitors:

Medicines group: Alpha glucosidase inhibitors

Hot Topics

Other services:

We are in social networks:

Our partners:

Alpha-glucosidase inhibitors

Mechanism of action

pros

Minuses

Indications

Contraindications and side effects

Directions for use and doses

Precautionary measures

File contents Oral hypoglycemic therapy

Alpha glucosidase inhibitors, which reduce carbohydrate absorption

3. Alpha-glucosidase inhibitors (Acarbose)

Oral hypoglycemic drugs: list, principle of their action

Types of oral glucose-lowering medications

Biguanide derivatives

Sulfonylurea derivatives

Alpha-glucosidase inhibitors

Thiazolidinedione derivatives (glitazones)

Glinide derivatives

Incretins

SGLT2 inhibitor derivatives

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