Modern medicine never stops looking for more and more new drugs for the treatment of type 2 diabetes. There are several groups of medications that make life easier for diabetics, reduce the risk of dangerous complications, and slow down or prevent the onset of the disease in people who are glucose-tolerant.
The drugs are selected individually for each person, because they have a different mechanism of action and different benefits. Some tablets for type 2 diabetes can be taken in combination with each other, thereby increasing their overall therapeutic effect.
First of all, preference is given to drugs with minimal risk of hypoglycemia: biguanides, gliptins, incretins. If a person suffers from obesity and arterial hypertension, incretins are better suited - they allow you to lose weight and regulate blood pressure.
Biguanide dosage regimen: The initial dose of metformin is 500 mg 2-3 times a day after meals. The next dose increase is possible approximately 2 weeks after the start of therapy. The maximum daily dosage of this medicine should not exceed 3000 mg. The gradual increase is due to the fact that there are fewer side effects from the gastrointestinal tract.
The latest generation of diabetes medications are taken 1 tablet (25 mg) per day, regardless of meals.
Incretins: medications in this group are presented in the form of injection solutions. They are administered 1 or 2 times a day, depending on the generation.
If monotherapy gives poor results, the following combinations of hypoglycemic agents are used:
The first two combinations have a minimal risk of developing hypoglycemia, and their weight remains stable.
Prescription regimen for sulfonylurea drugs: it depends on the generation of the drug. Usually the drugs are taken once a day in the morning. As the dosage increases, doses can be divided into morning and evening.
Scheme for prescribing glinides: A peculiarity of the use of these drugs is that drugs in this group are timed to coincide with meals and are taken immediately before it. Usually the tablets are taken 3 times a day.
Alpha-glucosidase inhibitors: The effectiveness of taking medications is observed only if you take the tablets immediately before meals. The initial dose of 50 mg is taken 3 times a day. The average daily dosage is 300 mg. Maximum – 200 mg 3 times a day. If necessary, the dose is increased after 4-8 weeks.
The drugs are taken 1-2 times a day depending on the generation. The timing of meals does not affect their effectiveness. If necessary, increase the dosage, it is increased after 1-2 months.
The doctor selects certain groups of medications, taking into account the individual characteristics of the person: concomitant diseases, excess weight, problems with the cardiovascular system, diet, etc.
It is prohibited to independently select or change the endocrinologist’s prescriptions!
| Group of drugs | Trade name | Manufacturer | Maximum dosage, mg |
| Biguanides | Siofor | Berlin-Chemie, Germany | 1000 |
| Diabetes | Servier Laboratories, France | 60 | |
| Amaryl | Sanofi-Aventis, Germany | 4 | |
| Glyurenorm | 30 | ||
| Glibenez retard | Pfizer, France | 10 | |
| Maninil | Berlin-Chemie, Germany | 5 mg | |
| Incretins | Baeta | Eli Lilly and Company, Switzerland | 250 µg/ml |
| Novo Nordisk, Denmark | 6 mg/ml | ||
| Januvia | Merck Sharp and Dome B.V., The Netherlands | 100 | |
| Galvus | Novartis Pharma, Switzerland | 50 | |
| Ongliza | AstraZeneca, UK | 5 | |
| Tragenta | Boehringer Ingelheim International, Germany | 5 | |
| Vipidia | Takeda Pharmaceuticals, USA | 25 | |
| Alpha-glucosidase inhibitors | Bayer, Germany | 100 | |
| NovoNorm | Novo Nordisk, Denmark | 2 | |
| Starlix | Novartis Pharma, Switzerland | 180 | |
| Pioglar | Sun Pharmaceutical Industries, India | 30 | |
| Avandia | GlaxoSmithKline Trading, Spain | 8 |
Among all the drugs in this group, methyl biguanide derivatives have gained the greatest popularity. Its mechanisms of action are presented in the form of a decrease in glucose production by the liver and a decrease in insulin resistance in muscle and fat tissue.
The main active ingredient is metformin. Preparations based on it:
Main advantages:
Flaws:
Contraindications:
The main mechanism of action is stimulation of the secretion of its own insulin. The main active ingredients and drugs for type 2 diabetes in this group are:
Some medications are available in a prolonged form - referred to as MV (modified release) or retard. This was done in order to reduce the number of pills taken per day. For example, Glidiab MV contains 30 mg of the substance and is taken once a day, even if the dose is increased, and regular Glidiab - 80 mg, the dose is divided into morning and evening.
The main advantages of the group are:
Flaws:
Contraindications:
This is the general name for hormones that stimulate the production of insulin. These include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Endogenous (own) incretins are produced in the gastrointestinal tract in response to food intake and are active for only a few minutes. For people with diabetes, exogenous (coming from outside) incretins were invented, which have longer activity.
Mechanisms of action of glucagon-like peptide-1 receptor agonists:
Active ingredients and drugs that mimic the action of GLP-1:
Advantages:
Flaws:
Contraindications:
Scientifically, they are called DPP-4 inhibitors or dipeptidyl peptidase type 4 inhibitors. They also belong to the group of incretins, but they are more advanced. The mechanism of action is determined by the acceleration of the production of the gastrointestinal tract's own hormones, which stimulate the synthesis of insulin in the pancreas in accordance with the concentration of sugar. They also reduce glucagon production in a glucose-dependent manner and reduce glucose production by the liver.
There are several substances and their preparations:
Contraindications:
The main mechanism of action is to slow down the absorption of carbohydrates in the intestine. The substances reversibly inhibit the activity of enzymes responsible for the breakdown of disaccharides and oligosaccharides to glucose and fructose in the lumen of the small intestine. In addition, they do not affect pancreatic cells.
This group includes the substance acarbose, which is part of the Glucobay product.
Advantages of the drug: 
Main contraindications:
The main mechanism of action is stimulation of insulin production. Unlike other pharmacological groups, they cause an increase in insulin secretion in the first 15 minutes after a meal, thereby reducing the “peaks” of blood glucose concentrations. The concentration of the hormone itself returns to its original value 3-4 hours after the last dose.
When the concentration of sugar in the blood is low, there is a slight stimulation of insulin synthesis, which helps to avoid hypoglycemia when skipping meals.
The main substances and preparations are:
Benefits of the group:
Flaws:
Contraindications:
Another name for them is glitazones. They are a group of sensitizers - they increase the sensitivity of tissues to insulin, that is, they reduce insulin resistance. The mechanism of action is to increase glucose utilization in the liver. Unlike sulfonylureas, these drugs do not stimulate the beta cells of the pancreas to produce insulin.
The main substances and their preparations are:
General benefits:
Flaws:
Contraindications:
They try not to prescribe insulin drugs until the last minute - at first they make do with tablet forms. But sometimes insulin injections become necessary even at the very beginning of treatment.
Indications:
Sugar-lowering medications are far from the only ones that diabetics need. There are several groups of medications that help maintain health, prevent complications due to type 2 diabetes from developing, or treat those that have already arisen. Without these medications, quality of life can deteriorate dramatically.
Hypertension together with diabetes form a truly explosive mixture - the risk of heart attacks, strokes, blindness and other dangerous complications increases. To reduce the likelihood of their development, diabetics are forced to monitor their blood pressure more carefully than others.
Groups of antihypertensive drugs:
Most often, ACE inhibitors are prescribed for type 2 diabetes. This group includes:
They are a group of substances that help reduce low-density lipoprotein and cholesterol levels in the blood. There are several generations of statins:
To maintain the health of people with type 2 diabetes, medications based on atorvastatin and rosuvastatin are most often used.
Drugs whose active ingredient is atorvastatin:
Based on rosuvastatin:
Positive effects of statins:
It is a metabolic agent and endogenous antioxidant. Used to regulate lipid and carbohydrate metabolism, stimulate cholesterol metabolism. The substance helps reduce blood glucose concentrations, increase glycogen in the liver and overcome insulin resistance.
Preparations based on it have the following positive effects:
Medicines based on thioctic acid are available in different dosages and release forms. Some trade names:
Diabetics take these drugs for polyneuropathy - loss of sensitivity due to damage to nerve endings, mainly in the legs.
Neuroprotectors are a combination of several groups of substances, the purpose of which is to protect brain neurons from damage; they can also have a positive effect on metabolism, improve the energy supply of nerve cells and protect them from aggressive factors.
Types of neuroprotectors:
Drugs of these groups are used by people with type 2 diabetes who have been diagnosed with diabetic or hypoglycemic encephalopathy. Diseases arise due to metabolic and vascular disorders due to diabetes.
Contraindications to the use of alpha-glucosidase inhibitors:
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.
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:
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 of dipeptidyl peptidase-4 inhibitors 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.
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
| Group of drugs | Mechanism of action |
| Sulfonylureas | |
| Meglitinides and phenylalanine derivatives | Stimulation of insulin secretion |
| Biguanides | Reduced liver glucose production Reduced insulin resistance in muscle and fat tissue |
| Thiazolidinediones (glitazones) | Reduced insulin resistance in muscle and fat tissues Reduced liver glucose production |
| α-glucosidase inhibitors | Decreased absorption of glucose in the intestine |
| Glucagon-like peptide-1 agonists | Glucose-dependent stimulation of insulin secretion and restoration of the first phase of insulin secretion Glucose-dependent decrease in glucagon secretion and reduction in liver glucose production Slowing gastric emptying Reducing food intake |
| Dipeptidyl peptidase-4 inhibitors (gliptins) | Glucose-dependent stimulation of insulin secretion Suppression of glucagon secretion Decreased glucose production by the liver Slowing gastric emptying |
Drugs that help reduce insulin resistance
Metformin
Metformin is the only biguanide currently used due to the risk of spontaneous lactic acidosis when taking phenformin and buformin. The drug has a fairly short half-life, practically does not bind to plasma proteins, and has a lesser effect on the electron transport chains in mitochondrial membranes - thus, it has virtually no risk of developing spontaneous lactic acidosis.
Metformin is a drug with extrapancreatic (peripheral) action; endogenous or exogenous insulin is required for its effects to occur. Main mechanisms of action:
1) Reduced liver glucose production and a decrease in fasting glucose levels, associated with a decrease in hepatocyte IR and a decrease in uncontrolled glucose production by the liver.
2) Reduced insulin resistance: improved insulin receptor tyrosine kinase function and GLUT-1 and GLUT-4 translocation leads to increased glucose utilization in skeletal muscle.
3) Activation of anaerobic glycolysis, decreased glucose absorption in the small intestine, decreased postprandial glycemia.
Indications for the use of metformin: type 2 diabetes with a predominance of insulin resistance (with obesity) and fasting hyperglycemia in combination with non-drug methods (diet, exercise). In this group of patients, metformin is the drug of first choice.
Initial The dose of metformin is usually 500 mg per day; to correct morning hyperglycemia, the drug is prescribed at 22-23 hours. Taking the drug at 22:00 effectively reduces the increased production of glucose by the liver at night and early in the morning and normalizes nocturnal and fasting glycemia. Efficient daily dose of metformin - ≈ 2000 mg. The maximum daily dose of the drug is 3 g. Side effects are dyspeptic disorders (nausea, diarrhea), which is usually transient. While taking metformin, regular monitoring of blood lactate levels is necessary.
Before prescribing metformin, it is necessary to ensure that the patient has no contraindications to its use, otherwise there is a risk of developing a severe complication with high mortality - biguanide-associated lactic acidosis.
Contraindications to the use of metformin:
1) Diseases accompanied hypoxia(cardiovascular and respiratory failure, anemia, history of lactic acidosis, infectious diseases).
2) Renal dysfunction(serum creatinine more than 120-130 µmol/l, GFR less than 50 ml/min).
3) Alcohol abuse, severe liver pathology(cirrhosis, chronic active, viral and infectious hepatitis). If transaminases increase more than 2 times, you should refrain from prescribing the drug.
4) Pregnancy, lactation.
5) Type 1 diabetes, diabetic ketoacidosis.
6) Metformin must be temporarily discontinued (3-7 days) before abdominal surgery and studies using radiocontrast agents.
Thiazolidinediones
Thiazolidinediones (pioglitazone, rosiglitazone) are agonists of peroxisome proliferator-activated receptor γ-PPAR. When used, nuclear receptors are stimulated, the transcription of insulin-sensitive genes is modulated, which increases the activity of endogenous insulin, i.e. improves insulin sensitivity, primarily in fat and muscle tissue.
Thiazolidinediones, in accordance with the ADA and EASD Type 2 Diabetes Management Algorithm 2008, are classified as second-line therapy (“less well-proven therapy”).
Contraindications:
Pregnancy and lactation;
Liver pathology, increased transaminase (ALT) levels >2.5 times;
Heart failure.
When using drugs, side effects may develop (increased levels of transaminases, decreased hemoglobin levels, the appearance of edema, weight gain by an average of 4-5 kg); Contraindications to rosiglitazone are currently being clarified.
Drugs that affect insulin secretion
Drugs that stimulate insulin secretion cause a decrease in glycemic levels mainly by stimulating the synthesis and secretion of insulin. This group of drugs affects the secretory defect of β-cells of the pancreas, which is one of the main links in the pathogenesis of type 2 diabetes and is present (to varying degrees) in every patient with this disease.
Groups of drugs that stimulate insulin secretion:
Sulfonylureas (SMU);
Prandial glycemic regulators (meglitinides).
Sulfonylureas
Mechanism of action: binding to specific receptors on the membranes of β-cells of the pancreas activates Na + -K + -ATPase, which causes depolarization of the cell membrane, blockade of potassium channels and activation of calcium channels. The increased entry of calcium ions into the cell leads to an increase in the concentration of intracellular calcium. An increase in intracellular calcium stimulates the synthesis and secretion (release of previously synthesized hormone from secretory intracellular granules into the bloodstream) of insulin.
Sulfonylureas in accordance with the Algorithm
ADA and EASD, 2008 refers to therapy with well-proven therapy (step 2 therapy); are recommended for use if lifestyle modification in combination with metformin is ineffective.
Contraindications:
Type 1 diabetes, diabetic ketoacidosis;
Pregnancy and lactation;
Pathology of the liver and kidneys (for kidney pathologies, the use of gliquidone, gliclazide, repaglinide is allowed).
According to the degree of connection with the membrane receptors of the β-cells of the pancreas, 3 generations (generations) of PSM are distinguished. First generation drugs (chlorpropamide, etc.), introduced into clinical practice in the 1950s, are currently of only historical interest: the strength of their connection with receptors is minimal, which required their administration in high doses (hundreds of milligrams - grams), which increased the risk of side and toxic effects.
Second generation PSM are characterized by a much stronger connection with specific membrane receptors of β-cells of the pancreas; they are effective in significantly lower doses (milligrams to tens of milligrams). Currently, generation II PSMs are widely used in clinical practice (gliclazide, glibenclamide, gliquidone). Glimepiride is presented as a third-generation PSM in clinical practice.
Table 7 summarizes the features of some PSMs.
Table 7
Sulfonylureas
Meglitinides
Drugs in this group include repaglinide and nateglinide. The binding of meglitinides to specific receptors on the membranes of β-cells of the pancreas provides rapid and short-term stimulation of insulin secretion. Due to their short-term effect, they are used immediately before meals according to the principle “there is a meal - there is a drug intake, no food intake - there is no drug intake.”
1.7.3.3. α-glucosidase inhibitors
A representative of this group is acarbose. The drug reversibly inhibits intestinal a-glucosidases, which break down slowly digestible carbohydrates into glucose in the small intestine. The action of acarbose reduces the absorption of glucose from the gastrointestinal tract into the blood, which reduces glycemia, primarily postprandial. The initial dose of acarbose is 50 mg once a day before meals, followed by an increase of 50 mg once a week to a dose of 50 mg 3 times a day. If necessary, the dose can be further increased to 100 mg 3 times a day (take the drug immediately before or during meals).
Indication: type 2 diabetes with ineffective diet and physical activity with a predominance of hyperglycemia after meals (postprandial).
Contraindications:
Type 1 diabetes, diabetic ketoacidosis;
Pregnancy and lactation;
Diseases of the gastrointestinal tract.
The glucose-lowering drugs of the main groups are comparable in their effects on carbohydrate metabolism, as illustrated by the dynamics of glycosylated hemoglobin (HbA). Data on the comparative effectiveness of the BSC are presented in Table 8.
This chapter contains four sections. The first and second, which deal with issues related to glucose-lowering drugs, are of interest to patients with NIDDM; the third and fourth, which talk about herbal medicine, medicinal preparations, vitamins and minerals, are useful for all diabetics to study, regardless of their classification. Note that information about vitamins and minerals can equally be attributed to nutrition and diet or to medications. We chose the latter because there are quite a few combination preparations containing vitamins and minerals, and these preparations are usually sold in pharmacies, not stores with diabetic products, that is, they are perceived by patients as medicine. As for nutrition, diet and the content of nutrients in foods, we will discuss this in the next chapter.
It has already been noted more than once that in the treatment of type I diabetes, the leading role is given to insulin, and the auxiliary role is given to rational nutrition; In the case of type II diabetes, the opposite is true: diet comes first, medications come second. The main medicine is one or another glucose-lowering drug (in common parlance - tablets), which is prescribed by an endocrinologist. There are quite a lot of these drugs, but it would be more correct to say this: there are a limited number of different drugs, but for each of them there are several trade names. Thus, it is necessary to know both the medical (general) name of the drug and the specific names under which it is given to you at the pharmacy.
Oral hypoglycemic drugs can be characterized in the same way as insulins: the beginning of their action (counting from the moment of administration); the time when the drug begins to act with full effectiveness; duration of the period of effective action; and, finally, the full duration of the drug. In addition, depending on their chemical composition and molecular structure, oral hypoglycemic drugs are divided into the following groups: 1. Drugs that stimulate insulin secretion. This group includes traditional sulfonylureas (SMUs) and the recently introduced Nonovorm (repaglinide, a benzoic acid derivative) and Starlix (nateglinide, a phenylalaline derivative).
2. Biguanides, which increase cell sensitivity to insulin.
3. Alpha-glucosidase inhibitors, which slow down the absorption of glucose from the intestine into the blood.
4. Sensitizers - glitazones, which also increase the sensitivity of peripheral tissues to insulin.
The PSMs most commonly used in the treatment of type II diabetes include three subgroups (see Table 10.1): first-generation drugs, which are now practically not used (the most famous of them was butamide); second generation drugs, such as Maninil and Diabeton, which are more effective; The third generation drug Amaryl, which has a number of advantages compared to earlier PSMs. Within this category of drugs, there are nine main drugs (their names are given in Table 10.1 in large print), known to patients under approximately forty different names (these are given in Table 10.1 in regular print). There are much fewer biguanides than PSM, three or four varieties, and currently only metformin (Siofor) is used in the treatment of diabetes. Why? For the reason that many medications, including glucose-lowering drugs, can cause unpleasant side effects.
Before prescribing any drugs, especially biguanides, the doctor must evaluate all contraindications so that the drug does not worsen the patient’s condition. This has been observed with biguanides, which is why the drugs in this group were banned in the United States thirty years ago. Then it turned out that, when prescribed correctly, they help some patients (especially those who are overweight) to normalize sugar levels, and now biguanides have returned to medical practice. Their valuable feature is that drugs in this group do not force the pancreas to produce more insulin, but reduce the absorption of sugars and fats from the intestines and, as noted above, promote better absorption of sugar by cells.
There is no hypoglycemia when using them.
Alpha-glucosidase inhibitors are represented by acarbose (the drug glucobay from the German company Bayer) and miglitinol (gliset). They have a special role: if PSM and the recently appeared Novonorm and Starlix reduce blood sugar levels, causing the pancreas to secrete more insulin, then acarbose-glucobay and miglitinol do not affect beta cells or peripheral tissues, but simply slow down the breakdown of complex sugars in the intestine .
What does it mean? Complex sugars contained in food must be broken down in the upper intestine into simple sugar (glucose), and only after this glucose is absorbed into the blood in the lower intestine. Alpha-glucosidase inhibitors inhibit the action of the digestive enzyme, so that, once in the lower part, complex sugars do not enter the blood. This may cause unpleasant side effects - bloating and diarrhea. Note that these drugs can be combined with glucose-lowering medications and insulin, but not on your own initiative, but on the advice of a doctor. These drugs are prescribed only to adults; take them three times a day before meals, a single dose of glucobay is from 0.05 to 0.2 g.
Sensitizers (glitazones) are, as already mentioned, substances that increase the sensitivity of peripheral tissues to insulin, reducing insulin resistance. Several years ago, in the USA and a number of other countries, troglitazone (rezulin) began to be used, probably the first or one of the first sensitizers. There was hope that rezulin could change the lives of patients with IDDM who do not tolerate insulin well, since it could be used to reduce doses and the number of injections. In previous editions of the Handbook, we warned readers that rezulin is not registered in Russia, is not used by our doctors, and that you need to be very careful with it - this drug can cause liver damage, it is taken under the supervision of a doctor and a biochemical blood test is done monthly ( there have been deaths abroad). Currently, rezulin is widely withdrawn from medical practice. As for Actos, the next generation sensitizer, it is already being used in our country. Actos can be prescribed as the only treatment or, as part of complex therapy, in combination with PSM, metformin (type II diabetes) and insulin (type I diabetes). Actos not only increases the sensitivity of muscle and fat tissue to insulin, but also reduces the production of glucose in the liver and reduces the risk of cardiovascular disease. The disadvantage of Actos is that it contributes to weight gain in patients. Note that this is a new drug, and doctors are still gaining experience in its effective use.
With these preliminary notes in mind, review Table 10.1, which provides information about glucose-lowering medications.
Table 10.1. Oral hypoglycemic drugs.
Notes: 1. Explanation of abbreviations and abbreviations: PSM - sulfonylurea drugs; Beginning - the beginning of the sugar-lowering effect (the beginning of the unfolding of the drug from the moment of administration); Max. ED - time to achieve effective action (time of complete unfolding from the moment of administration); Duration ED - period of effective action; Duration P - the full duration of the drug. The daily dose is given in minimum and maximum values - separated by a dash.
2. In Russia you can find tableted hypoglycemic drugs produced in the following countries: Russia, Ukraine, Belarus, USA, Canada, Germany, Hungary, Finland, Croatia, India, Israel, etc.
3. The latest drugs are produced by the following companies: amaryl - Aventis, Germany - France; novonorm - Novo Nordisk, Denmark; Starlix - Novartis; actos - "Lilly", USA.
Now let's comment on Table 10.1.
First of all, we note that the drugs are contained in bottles or on plastic strips, and the strips and bottles are in cardboard boxes on which the names of the drugs, storage conditions, expiration dates and all other information are written - exactly the same as in the case of insulins. Of course, you should not use expired medications.
The second circumstance: medications are in the form of tablets intended for oral administration, but the same drug can be produced in the form of “small” and “large” tablets. For example, maninil: there are tablets that contain 0.0015 g of the drug, and there are tablets containing 0.005 g. Therefore, the dose in Table 10.1 is given not in the number of tablets, but in grams and fractions of a gram. You should carefully monitor how much of the drug you take; its content in each tablet is indicated on the bottle and on the packaging.
Third. We see that typical second-generation PSMs - for example, glurenorm, diabeton, maninil - unfold in thirty to forty minutes, achieve effective action in 1.5–2 hours, act with full effectiveness from 6 to 8 hours, with a full duration of action of 8– 12 o'clock. After studying Chapter 8, we already know that these numbers are quite arbitrary; on different patients, and even on the same patient in different conditions, the same medicine acts somewhat differently. We can also note that the time characteristics of PSM do not differ to the same extent as those of “short” and long-acting insulins (the exception is chlorpropamide, which lasts up to sixty hours).
A natural question arises: why do we need so many drugs? Why not make do with one - for example, Maninil? But let us remind you that no two diabetes are the same. If we turn to type II diabetes, the disease can be very mild (diet and herbs are enough), it can be a little more severe (diet and mild PSM are enough), it can be of moderate severity, but not progress (diet and taking a certain drug are enough) , may progress (then it is necessary to move from weak-acting drugs to stronger ones and even to insulin). Thus, we need a whole range of medicines to use one or another remedy depending on the situation. The main difference between hypoglycemic drugs lies in the strength of their effect, in their hypoglycemic activity: for example, butamide is one of the weakest drugs, Diabeton is a stronger drug, and Maninil is the strongest.
However, this is not the only difference; there are also other factors: - how well the drug is absorbed from the intestines; - over what period is it eliminated from the body (more precisely, they talk about the half-life of the drug); - is the drug excreted by the liver and kidneys or only by the liver, like glurenorm (the kidneys are protected); - at what phase of insulin secretion does the medicine act with the greatest activity; - how the drug is tolerated by different categories of patients (for example, the elderly); - how significant is the effect of addiction to the drug; - what are the side effects of the drug, harmful or beneficial.
Regarding the last point, we note as an example that Diabeton and a number of other drugs simultaneously protect blood vessels, but this beneficial property is not the main indicator for their purpose. Let's assume that diabetic disease occurs in a mild form, with low blood sugar levels, which, in principle, could be compensated by diet. If the patient violates the diet, then to compensate it is necessary to use a weak remedy - glucobay, since a stronger one will cause hypoglycemia in him.
Yes, the same hypoglycemia that we have already talked about more than once! It occurs not only with IDDM, but in cases where the patient takes a medicine that stimulates insulin secretion - PSM of the second or third generations, Novonorm or Starlix.
Let us briefly and qualitatively describe the mechanism of action of these glucose-lowering drugs. First of all, let us recall that type II diabetes, unlike IDDM, is not associated with the lack of its own insulin, but with other reasons. There is enough insulin, but it is partly defective and - again, partly! - is not able to perform its function as a “key”, that is, to open the “doors” of cells in front of glucose molecules. Thus, the therapeutic drug must either increase the overall secretion of insulin (so that the amount of “good”, defect-free insulin also becomes larger), or increase the sensitivity of cells to insulin - so that the available “good” insulin allows more molecules into the cells glucose.
At this stage of our reasoning, it should be noted that the secretion of insulin by the pancreas is a very complex biochemical process. It consists of two stages or phases, which doctors call the first and second peak of insulin secretion, respectively.
Now we can imagine the effect of insulin-stimulating drugs as follows: - all PSMs, similar in their chemical structure, as well as Novonorm and Starlix, act on the pancreas, “squeezing” it and forcing it to secrete more insulin; - Diabeton and Starlix are more active in the first phase of secretion (as doctors say, they restore the first or early peak of insulin secretion); - drugs such as maninil and first generation PSM are more active in the second phase of secretion; - all drugs (primarily maninil) can cause hypoglycemia.
Let us note the features of the newest drugs, which include Amaryl, Starlix and Novonorm. Amaryl, developed by the German company Hoechst (now Aventis), has been used in the USA and Germany since 1995, in Russia it has been approved for use since 1998 and is already available to our patients with type II diabetes. Its advantages compared to second-generation PSM drugs are as follows: - amaryl does not contribute to weight gain, and its negative effect on the cardiovascular system is less than that of other PSMs; - amaryl can be taken in smaller doses than, for example, maninil, and only once a day, regardless of meal time. It provides blood sugar regulation for 24 hours; - Amaryl is a “smooth” drug; it stimulates the sharp release of insulin into the blood to a lesser extent, making this process more uniform, which reduces the risk of hypoglycemia. Of particular note is the rarity of hypoglycemia and the fact that patients taking Amaryl and performing heavy physical work may not be afraid of a sudden drop in blood sugar.
Starlix and Novonorm are the first insulin-stimulating drugs that are not sulfonylurea derivatives. Starlix unfolds quite quickly, reaching its peak effect in one hour, does not affect the kidneys and liver, does not cause weight gain, and reduces the risk of hypoglycemia.
This drug works for 6-8 hours, so you need to take it three times a day, before breakfast, lunch and dinner. There is no need to select a dose: it is always standard - 120 mg. As for Novonorm, which is also taken three to four times a day, before each meal, its dose must be adjusted from a minimum of 0.5 mg to a maximum of a single dose of 4 mg. There is also a low risk of hypoglycemia when using this drug; side effects are the same as in the case of second-generation PSM.
Let us now turn to biguanides and recall that their mechanism of action is different from that of PSM - they do not stimulate the production of insulin by the pancreas, but increase the sensitivity of the cell to insulin. This mechanism is still not entirely clear, but metformin (Siofor) is known to promote weight loss, so it is usually used to treat obese patients with type II diabetes.
The availability of a wide range of glucose-lowering drugs has made it possible to develop a new strategy for compensating for type II diabetes - “combi” therapy, which combines treatment with two drugs.
Thus, the insulin-stimulating drugs Novonorm and Starlix are prescribed together with metformin; In addition, the drug Glibomet from Berlin-Chemie appeared, each tablet of which contains 2.5 mg of glibenclamide and 400 mg of metformin. This comprehensive approach to the treatment of type II diabetes allows one to simultaneously increase insulin secretion by beta cells and reduce insulin resistance in peripheral tissues.
Having dealt with medications, let’s move on to the issue of their use, that is, to therapy and possible scenarios for the course of type II diabetes.
Content
Today, there are oral glucose-lowering medications that help a person suffering from diabetes avoid insulin injections even if they are overweight. Pharmacies offer a huge selection of medications that help the patient maintain the required level of glycemia. For people who do not produce enough insulin, it is useful to learn about the properties and effects of the medications they are taking. This will help them consciously fight the disease.
In 2016, according to statistics from the World Health Organization, people with diabetes among the adult population of the planet accounted for 8.5%. It is no coincidence that scientists around the world have united to create effective drugs against this disease. Antihyperglycemic drugs are drugs created on the basis of chemical substances that can activate the secretion of insulin by the pancreas, slow down the production of glucose by the liver, or activate the use of sugar by the tissues of the human body.
A comparative table of the main classes of glucose-lowering drugs will help you understand the large number of antidiabetic drugs offered by pharmacology:
|
Advantages |
Flaws |
Trade names of drugs |
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|
Sulfonylurea derivatives |
Used for types 1 and 2 diabetes mellitus; compatible in combination with insulin dosages or other classes of hypoglycemic drugs; some of them are excreted by the intestines; have a hypoglycemic effect of up to 2%; third generation drugs quickly reach peak insulin secretion |
Provoke a feeling of hunger, promote weight gain; second generation drugs increase the risk of myocardial infarction when taken; have the side effect of hypoglycemia |
Maninil, Glibenclamide, Acetohexamide, Amaryl |
|
|
Within half an hour after taking the medicine, they cause insulin secretion; do not help increase insulin concentrations between meals; do not provoke the development of myocardial infarction |
Have a short validity period; promote weight gain in diabetics; do not give effect when taken for a long time; have a hypoglycemic effect of up to 0.8%, have hypoglycemia as a side effect |
NovoNorm, Starlix |
||
|
Biguanides |
Do not provoke feelings of hunger; activate the breakdown of fats; thin the blood; have a sugar-burning effect of 1.5-2%; reduce cholesterol levels |
Promote the formation of lactic acid, leading to poisoning of the body |
Avandamet, Glucophage, Siofor, Metfogamma |
|
|
Glitazones |
Reduce the amount of fatty acids in the blood; effectively reduce insulin resistance |
They have a hypoglycemic effect of up to 1.4%; increase the risk of death from vascular and heart diseases; contributes to an increase in the patient's body weight |
Aktos, Avandiy, Pioglar, Roglit |
|
|
Alpha-glucosidase inhibitors |
Does not lead to the development of hypoglycemia; reduces the patient's weight; reduces vascular atherosclerosis |
Have hypoglycemic activity up to 0.8% |
Miglitol, Acarbose |
|
|
Incretin mimetics |
No risk of hypoglycemia; do not affect the patient’s body weight; moderately reduce blood pressure |
Have low hypoglycemic activity (up to 1%) |
Ongliza, Galvus, Januvia |
Sugar-lowering drugs for type 2 diabetes, obtained from sulfonamide, by their action stimulating pancreatic cells to produce insulin, belong to the group of sulfonylurea derivatives. Medicines based on sulfonamide have an anti-infective effect, but when they are used, a hypoglycemic effect is observed. This property became the reason for scientists to develop sulfonylurea derivatives that can reduce glycemia. Several generations of drugs in this class can be distinguished:
The new generation of antidiabetic drugs differ from the previous two in varying degrees of activity of the main substances, which makes it possible to significantly reduce the dose of tablets and reduce the likelihood of undesirable therapeutic manifestations. The mechanism of action of sulfonylurea drugs is as follows:
It is not recommended to use sulfonylurea class sugar-lowering tablets for a long time due to the possibility of the patient developing resistance to the drug, which reduces the therapeutic effect. However, in type 1 diabetes, this approach will improve the course of the disease and lead to the ability to reduce the body's daily need for insulin.
Sulfonylurea antihyperglycemic drugs are prescribed if:
Contraindications to the use of drugs:
Side effects that occur when taking this type of glucose-lowering tablets:
Short-acting drugs that can rapidly increase insulin secretion through the functioning of the pancreas, thereby effectively controlling blood sugar levels after meals, are classified as glinides. If hyperglycemia occurs on an empty stomach, the use of glinides is not advisable, since they will not be able to stop it. These glucose-lowering medications are prescribed to a patient if the concentration of glucose in his blood cannot be normalized with exercise and diet alone.
Medicines in this class should be taken before meals to prevent a sharp increase in glycemia during the digestion of food. And although medications related to glinides must be taken frequently, it effectively stimulates the secretion of insulin in the body. Contraindications to the use of these funds include:
When therapy with glinides, there is a possibility of developing hypoglycemia. There are known cases of patient visual impairment due to fluctuations in blood glucose levels during long-term use of these glucose-lowering tablets. Undesirable effects during treatment with glinides include:
Medicines of the meglitinide group belong to the glinide class and are represented by tableted drugs repaglinide (Novonorm) and nateglinide (Starlix). The mechanism of action of these tablets is based on their effect on special receptors that open calcium channels in the membranes of beta cells, due to which the influx of calcium initiates increased secretion of insulin. This leads to a decrease in glycemia after eating. The likelihood of hypoglycemia between two meals is reduced.
The use of Novonorm or Starlix tablets for the treatment of diabetes promotes more powerful insulin production than when the patient takes glucose-lowering tablets of sulfonylurea derivatives. The onset of action of Novonorm occurs after 10 minutes, which prevents the absorption of excess glucose after the patient eats. The activity of Starlix is quickly lost and the insulin level becomes the same after 3 hours. The convenience of using these drugs is that they do not need to be taken without food.
Hypoglycemic drugs biguanides are guanidine derivatives. They, unlike sulfonylurea derivatives and glinides, do not provoke the release of insulin due to overstrain of the pancreas. Biguanides are able to slow down the formation of glucose by the liver, enhance the process of using sugar by body tissues, which reduces insulin resistance. This group of glucose-lowering drugs affects carbohydrate metabolism by slowing down the absorption of glucose in the human intestine.
Metformin belongs to the biguanide class. The doctor prescribes sugar-lowering tablets of this class to patients who have complications with diabetes and the need to lose weight. In this case, the dose of metformin is gradually increased by selecting it to the desired result. Patients with type 1 diabetes are prescribed metformin together with the required dose of insulin. This medicine should not be used if:
Among the contraindications of this hypoglycemic agent are:
The next class of glucose-lowering drugs are glitazones. Their chemical structure is based on a thiazolidine ring, which is why they are also called thiazolidinediones. Since 1997, blood sugar-lowering tablets pioglitazone and rosiglitazone have been used as antidiabetic drugs in this class. Their mechanism of action is the same as that of biguanides, that is, it is based on increasing the sensitivity of peripheral tissues and the liver to insulin and reducing lipid synthesis in cells. Glitazones reduce tissue insulin resistance to a greater extent than metroformin.
Women taking glitazones are advised to increase contraception, because these medications stimulate the appearance of ovulation even at the initial stage of menopause. The maximum concentration of the active substances of these drugs in the patient's body is observed 2 hours after oral administration. Side effects of this drug include:
Glitazones should not be prescribed for:
Another class of new glucose-lowering drugs are Incretin mimetics. Their mechanism of action is based on blocking the functioning of enzymes that break down the biologically active substances incretins, which promote the production of insulin by the pancreas. As a result, the effect of incretin hormones is prolonged, the production of glucose by the liver is reduced, and gastric emptying is slowed down.
Incretin mimetics include 2 groups: glucagon-like polypeptide-1 receptor agonists (GLP-1 agonists) and dipeptidyl peptidase 4 inhibitors. GLP-1 agonists include drugs such as exenatide, liraglutide. These medications are suitable for patients who are obese because treatment with them does not affect the patients' body weight. There is a low risk of hypoglycemia with monotherapy with these antihyperglycemic tablets.
The use of incretin mimetics is prohibited for chronic diseases of the intestines, kidneys and pregnant women. Among the undesirable effects of the tablets are:
Hypoglycemic drugs dipeptidyl peptidase 4 inhibitors belong to the class of incretin mimetics. They are represented by the drugs vildagliptin, sitagliptin, saxagliptin. Their valuable quality is the improvement of glycemia due to the restoration of normal pancreatic function of the patient. Contraindications and side effects of these drugs are the same as those of incretin mimetics.
Doctors resort to prescribing combined glucose-lowering drugs if monotherapy for diabetes does not bring the desired effect. One medicine sometimes does not cope with several of the patient's health problems that accompany the disease. In this case, one combined antihyperglycemic agent replaces several drugs to lower the patient’s blood glucose levels. In this case, the risk of side effects is significantly reduced. Doctors consider combinations of thiazolidinediones and metformin in glucose-lowering tablets to be the most effective.
The second most effective is a combination of sulfonylurea and biguanide. An example of such a combination is Glibomet tablets. It is prescribed when monotherapy with one of the components (biguanide or sulfonylurea) has not brought the desired result. This medicine is contraindicated in children and pregnant women, people with impaired renal and liver function. The hypoglycemic effect occurs 1.5 hours after taking the drug and lasts up to 12 hours. Taking this medicine does not affect the patient's weight.
The price level for hypoglycemic drugs within Moscow varies, so it is worth comparing the cost of drugs in pharmacies in different regions of the capital and considering delivery offers:
|
Name of medicine |
Pharmacy name |
Price (RUB) |
|
|
Sulfonylurea derivatives |
Maninil 3.5 mg |
ElexirPharm |
|
|
Novonorm 1mg |
ElexirPharm |
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|
Biguanides |
Siofor 850 mg |
heart |
|
|
Glitazones |
Pioglar 30 mg |
TRIKA on Sokolinka Samson-Fama |
|
|
Alpha-glucosidase inhibitors |
Acarbose 50 mg |
Capitals on Tolbukhina |
|
|
Incretin mimetics |
Galvus 50 mg |
ElexirPharm |
