Home Removal Oral hypoglycemic drugs: list, principle of their action. Alpha-glycosidase inhibitors Alpha-glucosidase inhibitors drugs

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Oral hypoglycemic drugs: list, principle of their action. Alpha-glycosidase inhibitors Alpha-glucosidase inhibitors drugs

Contraindications to the use of alpha-glucosidase inhibitors:

Inflammatory bowel diseases;
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 caused by 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 to obtain full effect may take up to three months.

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 preventive agent. diabetes mellitus type 2 and reducing 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.

Among side effects- 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 new class hypoglycemic drugs, which include 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 main role Glucose-dependent insulinotropic (GIP) and glucagon-like peptides (GLP-1) play a role in this process. This happens in 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 of dipeptidyl peptidase-4 inhibitors is sitagliptin, which is marketed under trade name Januvia.

Januvia stimulates insulin secretion and also suppresses the secretion of the hormone glucagon. This occurs only under conditions of hyperglycemia. With normal glucose concentrations, the above mechanisms are not activated, this helps to avoid hypoglycemia, which happens during treatment hypoglycemic drugs 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 newest group 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 phenomena with the use of SGLT2 inhibitors are a decrease blood pressure, as well as body weight. Among side effects medications may develop hypoglycemia and genitourinary infections.

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, they resort to combined treatment several oral hypoglycemic drugs. 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

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”, competitively and reversibly binding to the enzyme small intestine(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 (includes 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 diseases intestines, 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 pharmachologic 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 hypoglycemic agents. However, you should be aware that acarbose enhances the hypoglycemic effect of other oral medications used, which requires adjustment of their dose (downwards). 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.

At joint use 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 carbohydrate metabolism(insulin/glucagon primarily) – they interfere with 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 last effect there is an additional advantage of treatment with alpha-glucosidase inhibitors compared to insulin secretagogues.

Mechanism of action. Drugs in this group reversibly bind alpha-glucosidase enzymes (sucrose, maltose, isomaltose and glucoamylase) in the lumen small intestine. As a result, the breakdown of disaccharides and oligosaccharides (for example, sugar and starch) into glucose and fructose, which can only be absorbed in the intestine, 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 only slightly (

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 intestines. 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 decrease 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 carbon, 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 directories medicines(though without indicating the manufacturer and in the form of “Miglitol”), in clinical practice it is not actually used. IN 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 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, and also 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 its 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

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).

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

The information is provided for informational purposes only. Do not self-medicate. At the first sign of disease, consult a doctor. There are contraindications, a doctor's consultation is required. The site may contain content prohibited for viewing by persons under 18 years of age.

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.

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 included 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 intestines, 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.

UDC 615.032 DOI: 10.22141/2224-0721.14.1.2018.127096

Sokolova L.K.

State Institution “Institute of Endocrinology and Metabolism named after V.P. Komissarenko NAMS of Ukraine", Kyiv, Ukraine

Alpha-glucosidase inhibitors in clinical practice. Questions and answers

For cite: Miznarodnij endokrinologicnij zurnal. 2018;14(1):71-75. doi: 10.22141/2224-0721.14.1.2018.127096

Summary. The article is devoted to the use of drugs of the alpha-glucosidase inhibitor class in patients with diabetes mellitus.

C2> "0 ® For a practicing endocrinologist

/To Practicing Endocrinologists/

International journal of endocrinology

The most common chronic disease, along with arterial hypertension and obesity, is type 2 diabetes mellitus (DM). The number of people with carbohydrate metabolism disorders and the incidence of type 2 diabetes are constantly growing, which is primarily due to the increase in the number of obese patients, as well as the average life expectancy.

Currently, the need for an individual approach to the treatment of patients with carbohydrate metabolism disorders is recognized throughout the world; The priority task is to achieve an optimal balance between the effectiveness and safety of therapy.

In the absence of sufficient effect from non-drug measures, in patients with verified type 2 diabetes, as well as in persons with impaired fasting glycemia and/or impaired glucose tolerance, the addition of drugs that affect carbohydrate metabolism is indicated.

What is the mechanism of action of drugs of the α-glucosidase inhibitor class?

Drugs of the α-glucosidase inhibitor class are oral hypoglycemic agents that, by inhibiting intestinal α-glucosidases, reduce the enzymatic conversion of di-, oligo-, and polysaccharides into monosaccharides, thereby reducing the absorption of glucose from the intestine and postprandial hyperglycemia. They act in the upper part of the small intestine, where they reversibly block alpha-glucosidases (glucose-glucosidases).

amylase, sucrase, maltase) and thereby prevent the enzymatic breakdown of poly- and oligosaccharides. This prevents the absorption of monosaccharides (glucose) and helps reduce blood sugar levels that rise after meals. Inhibition of alpha-glucosidase occurs on the principle of competition for the active center of the enzyme located on the surface of the microvilli of the small intestine. By preventing an increase in the level of glycemia after a meal, drugs of this class significantly reduce the level of insulin in the blood, which helps to improve the quality of metabolic compensation, as evidenced by a decrease in the level of glycated hemoglobin. The use of α-glucosidase inhibitors as the only oral antidiabetic agent is sufficient to significantly reduce the severity of metabolic disorders in patients with type 2 diabetes that are not compensated by diet.

What drugs registered in Ukraine belong to the class of alpha-glucosidase inhibitors?

This class of drugs (a-glucosidase inhibitors, A10BF) are:

Acarbose (A10BF01);

Miglitol (A10BF02);

Voglibose (A10BF03).

Currently in Ukraine, the class of a-glucosidase inhibitors is represented by the drug Voxide (manufactured by Kusum Pharm), the active substance is voglibose.

© “Miznarodnij endokrinologichnij zurnal” / “International Endocrinological Journal” / “International Journal of Endocrinology” (“Miznarodnij endokrinologicnij zurnal”), 2018 © Vidavets Zaslavskiy O.Yu. / Publisher Zaslavsky A.Yu. / Publisher Zaslavsky O.Yu., 2018

For correspondence: Sokolova L.K., Institute of Endocrinology and Metabolism named after V.P. Komissarenko NAMS of Ukraine", st. Vyshgorodskaya, 69, Kyiv, 04114, Ukraine; e-mail: [email protected]

For correspondence: L. Sokolova, State Institution "V.P Komisarenko Institute of Endocrinology and Metabolism of the NAMS of Ukraine"; Vyshgorodska st., 69, Kyiv, 04114, Ukraine; e-mail: [email protected]

Is there a sufficient evidence base to support the use of drugs of the alpha-glucosidase inhibitor class in clinical practice for the treatment of patients with diabetes and/or persons with dysglycemia?

In the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) study for 3 years and 3 months. studied the effectiveness of acarbose (maximum dose 100 mg 3 times a day). Compared with placebo, the risk of developing T2DM with acarbose decreased by 25%.

Based on data obtained in studies on the prevention of diabetes in people with impaired glucose tolerance, it was concluded that lifestyle changes or the use of drugs (metformin, acarbose) in combination with diet therapy and increased physical activity lead to a reduction in the risk of developing diabetes. diabetes by 31-58% over 3-6 years.

These studies also confirmed that the determining factor in the prevention of T2DM is weight loss. In the case of the use of α-glucosidase inhibitors, weight loss is achieved by reducing the absorption of carbohydrates in the intestine.

Algorithm for prescribing oral hypoglycemic drugs (OHDs) according to IDF recommendations

Conventional approach

Alternative Approach

Picture 1

Algorithm for monitoring blood glucose levels - 2017

Treatment aimed at lifestyle modification (including weight loss with pharmacotherapy)

First level

A1C< 7,5 %

Monotherapy*

Metformin

If target level is not achieved after 3 months, switch to dual-component therapy

Initial A1C level > 7.5%

First level

Dual-component therapy

Metformin

or other I drug

first, basal insulin line

Kolesevelam

If target level is not achieved after 3 months, switch to triple therapy

Triple therapy

Metformin

or another first-line drug + second-line drug

Basal insulin DPP-4i

Kolesevelam

Bromocriptine short acting

1 ton I Insulin

therapy I Pr-

Triple therapy

other drugs

*The order of medications represents the intended hierarchy of use: the length of the line reflects the strength of the recommendation

If after 3 months the target level is not achieved, switch to insulin therapy or increase it

Add insulin or intensify your intake

See the algorithm for taking insulin

Minor side effects and/or possible benefits I Use with caution

Disease progression

Figure 2

Notes: A1C - glycated hemoglobin; GLP-1 RA - glucagon-like peptide-1 receptor agonists; SGLT-2i - sodium-dependent glucose cotransporter inhibitor; DPP-4i - dipeptidyl peptidase-4 inhibitor; TZD - thiazolidinedione; AGi - alpha-glucosidase inhibitor; SU/GLN is a sulfonylurea/glinide derivative.

The alpha-glucosidase inhibitor class is one of the safest drugs affecting postprandial glucose levels and insulin resistance. The STOP-NIDDM study clearly demonstrated the high effectiveness of acarbose in preventing type 2 diabetes in patients with impaired glucose tolerance. The main finding of the STOP-NIDDM study was that patients on active acarbose treatment had a 36% lower relative risk of developing type 2 diabetes than those in the placebo group. The relative risk of developing new cases of hypertension during active treatment decreased by 34%, myocardial infarction by 91%, and any recorded cardiovascular event by 49%. Thus, it has been shown that acarbose has a positive effect on the main cardiovascular risk factors - excess body weight, postprandial hyperglycemia and hypertension.

N.V. Pasechko et al. conducted a study of the effect of alpha-glucosidase inhibitors on body weight based on carbohydrate metabolism parameters. The results of the study showed that voglibose reduced the level of postprandial glycemia, Hb^, and also promoted weight loss.

Japanese researchers (Kawamori R. et al., 2009) studied the effectiveness of voglibose for the prevention of type 2 diabetes in 1780 people with impaired glucose tolerance (IGT) in a multicenter, randomized, double-blind study. Study participants were randomized to receive voglibose (n = 897) at a dose of 0.2 mg three times daily or placebo (n = 883). Treatment continued until the development of type 2 diabetes (primary endpoint) or normoglycemia (secondary endpoint); the follow-up period was 3 years. It was found that individuals with IGT who received voglibose had a low risk of progression to type 2 diabetes compared to placebo. Many more people in the voglibose group achieved normoglycemia than in the placebo group (599 of 897 versus 454 of 881). The authors concluded that taking voglibose in addition to lifestyle modification can reduce the risk of developing type 2 diabetes in people with IGT.

In the work of I.V. Chernyavskaya showed the modifying effect of voglibose on indicators of carbohydrate metabolism in individuals with impaired glucose tolerance and high cardiovascular risk.

At the 53rd Congress of the European Association for the Study of Diabetes, which took place from 11 to 15 September 2017 in Lisbon, the results of the ACE study were published. The researchers further emphasized the safety of the alpha-glucosidase inhibitor class in patients with type 2 diabetes and high cardiovascular risk, and also confirmed the benefits of using drugs of this class in the prevention of diabetes.

Clinical and experimental studies confirming the effectiveness and safety of the use of this class of drugs in patients with disorders of carbohydrate metabolism - from impaired glucose tolerance to clinically manifest type 2 diabetes - are described in the publications of Professor V.I. Pankiva. Apparently, the data from these studies can be extrapolated to the entire class of alpha-glucosidase inhibitors, since members of this class have a common mechanism of action.

Are drugs of the alpha-glucosidase inhibitor class included in modern international recommendations for the treatment of patients with diabetes?

α-glucosidase inhibitors are present in modern treatment algorithms for patients with type 2 diabetes of all the most influential professional associations, both foreign and Ukrainian.

According to recommendations for the management of patients with type 2 diabetes, indications for prescribing alpha-glucosidase inhibitors are unsatisfactory glycemic control due to diet; failure of treatment with sulfonylurea derivatives in patients with sufficient levels of insulin secretion; unsatisfactory control during treatment with metformin.

According to the instructions for use of the drug Voxid, the indications for use are:

Diabetes mellitus type 2 (with the ineffectiveness of diet therapy, the course of which should be at least 6 months, insufficient effectiveness of sulfonylurea derivatives against the background of a low-calorie diet);

Diabetes mellitus type 1 (as part of combination therapy);

Prevention of type 2 diabetes mellitus (in patients with impaired glucose tolerance in combination with diet and exercise).

What contraindications and side effects are typical for this class of drugs?

Contraindications to the use of alpha-glucosidase inhibitors are: diabetic ketoacidosis, liver cirrhosis, acute and chronic intestinal inflammation, gastrointestinal pathology with increased gas formation, ulcerative colitis, intestinal obstruction, large hernias, pregnancy and breastfeeding.

Features of the use of alpha-glucosidase inhibitors in the clinic

Alpha-glucosidase inhibitors are indicated for patients with diabetes mellitus when diet and exercise are ineffective with a predominance of hyperglycemia after meals.

Voxide is administered orally before each meal at a dose of 0.2 mg 3 times a day. If necessary, the dose can be increased to 0.3 mg 3 times a day, but the patient's condition must be carefully monitored. It is recommended to adjust the dose of the drug at intervals of 1-2 weeks. The tablets should be taken without chewing, with a small amount of liquid, immediately before meals.

Typically, for the first 10-15 days, Voxide is taken 0.2 mg 3 times a day immediately before or during meals, then the dose is gradually increased based on tolerability. This tactic of prescribing the drug can prevent or reduce gastrointestinal symptoms such as flatulence and diarrhea. In case of intestinal disorders caused by taking the drug, it is necessary to strictly follow a diet with limited carbohydrates and reduce its dose.

Contraindications to the use of Voxide are intestinal diseases accompanied by malabsorption, ulcers, diverticula, fissures, stenoses. Also, the drug should not be prescribed to persons under 18 years of age or during pregnancy or lactation.

Elderly patients are prescribed an initial dose of 0.1 mg 3 times a day. If necessary, the dose is increased to 0.2-0.3 mg 3 times a day.

An undoubted advantage of Voxide is also that it does not cause hypoglycemia during monotherapy. During treatment with this drug, you should limit your carbohydrate intake. Due to violation of dietary recommendations during treatment, flatulence and diarrhea may occur, reflecting the pharmacological effect of the drug. Voxide is not absorbed and, accordingly, has no systemic effects.

The drug can be combined with other sugar-lowering agents. It should be remembered that it enhances the hypoglycemic effect of other oral drugs, which requires a reduction in their dose. Otherwise, hypoglycemia may develop, which can only be stopped by taking pure glucose, since taking complex carbohydrates will be ineffective during treatment with Voxide.

It should also be remembered that the effectiveness of α-glucosidase inhibitors is significantly reduced when used together with antacids, sorbents, and enzymes that improve the digestion process.

A feature of this class of hypoglycemic drugs is their effectiveness when consuming large amounts of complex carbohydrates. If simple carbohydrates predominate in the patient’s diet, then treatment with alpha-glucosidase inhibitors does not provide a significant positive effect. This mechanism of action makes drugs in this group most effective for normal fasting blood glucose and a sharp rise after

eating. Also, these drugs do not increase body weight, which is an additional advantage when treating patients with overweight and/or obesity.

An important therapeutic effect of Voxide is the reduction of postprandial hyperinsulinemia and triglyceride levels in the blood. The significance of this fact is great, since lipoproteins saturated with triglycerides in patients with type 2 diabetes aggravate insulin resistance and are an independent risk factor for the development of atherosclerosis. The advantage of the drug is the absence of hypoglycemic reactions, which is especially important in elderly patients.

We have experience using Voxide in patients with type 2 diabetes, who are usually on combination glucose-lowering therapy. According to our data, the drug helps reduce postprandial glycemia and triglyceride levels, is well tolerated by patients, and has a small number of side effects.

As an example, a clinical case is presented

Patient K.T., 46 years old, entrepreneur, type 2 diabetes for 5 years. At the time of examination, the level of fasting glycemia was 6.9 mmol/l, postprandial glycemia 13.7 mmol/l, glycated hemoglobin 7.9%, body mass index - 32.2 kg/m2.

Blood pressure 130/80 mm Hg, lipidogram parameters: total cholesterol 4.2 mmol/l, LDL 2.1 mmol/l, HDL 1.0 mmol/l, TG 2.1 mmol/l.

Antihyperglycemic therapy was not systematic, representing the replacement of one tablet drug with another. Over the past two months, the patient, on the recommendation of a doctor, received metformin 1000 mg 2 times a day. Among the lifestyle features, it should be noted an unpredictable work schedule, irregular large meals, intense physical activity 2 times a week (gym). The patient refused to change his usual lifestyle, arguing that this was due to the peculiarities of his work. Based on the fact that the patient needed increased glucose-lowering therapy, as well as taking into account his wishes to lose weight and have the most simplified treatment regimen, a combination of metformin with alpha-glucosidase inhibitors (Voxide 0.2 mg before meals) was proposed.

Prescribing Voxide cannot significantly affect the usual lifestyle, does not require additional measurements of glycemic levels and is not associated with the risk of developing severe hypoglycemia.

A slight decrease in fasting blood glucose levels was noted during the first week. The most significant was a decrease in postprandial glycemia. During the first two weeks, the levels decreased by an average of 2 mmol/l and amounted to 8.3-9.8 mmol/l. The HbA1c indicator decreased by 1.2% and amounted to 3

MEPAGS^U endokrinologlcnij zurnal, ^ 2224-0721 (rpp^, ^ 2307-1427 (online)

Me1. 14, N0. 1, 2018

month 6.7%, which corresponds to the target level adopted by both treatment standards in our country and international standards. The dynamics of body weight loss over the 6-month observation period was 5.4 kg (108 kg initially, after 6 months - 102.6 kg), which is more than 5% of the initial weight.

Positive dynamics of the lipidogram were noted; the level of triglycerides was 1.7 mmol/l, which, in our opinion, is associated with a decrease in both carbohydrate absorption and the patient’s weight.

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 (Acarbose, Glyukobay) 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 is increased to 50-100 mg 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.

Contraindications

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.

Side effects

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.