What are incretins and incretinomimetics, which drugs from the group of dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 agonists are used in the treatment of diabetes? Today you will learn what these long and complex words mean, and most importantly, how to apply this knowledge.
This article will focus on completely new drugs-analogs of glucagon-like peptide 1 (GPP1) and dipeptidyl peptidase 4 (DPP4) blockers. These drugs were invented in studies of incretin hormones – those that are directly involved in the synthesis of insulin and the utilization of glucose in the blood.
Incretins and treatment of type 2 diabetes
To begin with, I will tell you what the incretins themselves are, as they are also called briefly. Incretins are hormones that are produced in the gastrointestinal tract in response to food intake, which increase the level of insulin in the blood. Incretins include two hormones-glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GIP receptors are located on beta cells of the pancreas, and GPP-1 receptors are located in various organs, so in addition to stimulating the production of insulin, activation of GPP-1 receptors leads to the appearance of other effects of this hormone.
Here are the effects that appear as a result of GPP-1:
Stimulation of insulin production by beta cells of the pancreas.
Suppression of glucagon production by alpha cells of the pancreas.
Slowing of gastric emptying.
Reduced appetite and increased feeling of fullness.
Positive effect on the cardiovascular and Central nervous systems.
Increasing the synthesis and production of insulin GPP-1 is a glucose-dependent process. This means that the hormone is activated and exerts its effect only when the blood glucose level is high, and as soon as the glucose decreases to normal numbers (about 4.5 mmol/l), the stimulation of insulin secretion stops. This is very important, because this mechanism protects the body from hypoglycemic reactions.
If the first and leading effect is clear: more insulin and less glucose, then the second one will probably be more difficult for you to understand. Glucagon is a pancreatic hormone produced by alpha cells. This hormone is the absolute opposite of insulin. Glucagon increases blood glucose levels by releasing it from the liver. Do not forget that in our body in the liver and in the muscles there are large reserves of glucose as an energy source, which are in the form of glycogen. By reducing the production of glucagon, incretins not only reduce the release of glucose from the liver, but also, again, increase the synthesis of insulin.
What is the positive effect of reducing gastric emptying in terms of treating diabetes? The fact is that most of the glucose in food is absorbed from the small intestine. Therefore, if food enters the intestines in small portions, then blood sugar will rise more slowly and without sharp jumps, which is also a big plus. This solves the problem of increasing glucose after eating (postprandial glycemia).
The value of reducing appetite and increasing satiety in the treatment of type 2 diabetes is generally difficult to overestimate. GPP-1 acts directly on the centers of hunger and satiety in the hypothalamus. So this is also a big and fat plus. And the positive effects on the heart and nervous system are only just being studied, and there are only experimental models available, but I’m sure we’ll learn more about these effects in the near future.
In addition to these effects, experiments have shown that GLP-1 stimulates the regeneration and growth of new pancreatic cells, and blocks the destruction of beta cells. Thus, this hormone protects the pancreas from depletion and helps to increase the mass of beta cells.
What would prevent us from using these hormones as medicine? These would be almost ideal medications, since they would be identical to human hormones. But the difficulty is that GPP-1 and GIP are very quickly destroyed (GPP-1 in 2 minutes, and GIP in 6 minutes) by the enzyme dipeptidyl peptidase type 4 (DPP-4).
But scientists have found a way out.
Today, there are two groups of drugs in the world that are somehow associated with incretins (since GPP-1 has more positive effects than GIP, it was economically profitable to work with GPP-1).
Drugs that mimic the action of human GPP-1.
Drugs that block the action of the DPP-4 enzyme, thereby prolonging the action of their hormone.
GPP-1 analogues in the treatment of type 2 diabetes
Currently, there are two analogs of GPP-1 on the Russian market: Bayetta (exenatide) and Victoza (liraglutide). These drugs are synthetic analogues of human GPP-1, but only the duration of action is much longer. They have absolutely all the effects of the human hormone that I mentioned above. This is undoubtedly a plus. Also, the advantages include a decrease in body weight by an average of 4 kg for 6-12 months. and a decrease in glycated hemoglobin by an average of 0.8-1.8 %. What is glycated hemoglobin and why you need to control it, you can find out by reading the article ” Glycated hemoglobin: how to pass?”.
The disadvantages include:
Only subcutaneous administration, i.e. no tablet forms.
The concentration of GLP-1 can increase by 5 times, which increases the risk of hypoglycemic conditions.
Only the effects of GLP-1 increase, the drug does not affect the Hypo.
In 30-40%, side effects may occur in the form of nausea, vomiting, but they are transient.
treatment of diabetes mellitus is available in disposable syringe pens (similar to insulin syringe pens) at a dose of 250 mcg in 1 mg. Handles are 1.2 and 2.4 ml. In one pack — one pen. Start treatment of diabetes mellitus with a dose of 5 mcg 2 times a day for 1 month to improve tolerance, and then, if necessary, the dose is increased to 10 mcg 2 times a day. Further increase in the dose does not increase the effect of the drug, but increases the number of side effects.
Baeta injection is done an hour before Breakfast and dinner, it can not be done after a meal. If the injection is missed, the next one is made at the appointed time according to the schedule. The injection is given subcutaneously in the thigh, abdomen, or shoulder. It cannot be administered intramuscularly or intravenously.
Store the drug in a dark, cold place, i.e. on the refrigerator door, do not allow freezing. The pen should be kept in the refrigerator every time after the injection. After 30 days, the syringe pen with the Baeta is thrown out, even if the drug remains in it, since after this time the drug is partially destroyed and does not have the proper effect. You can not store the drug used with the needle attached, i.e. after each use, the needle must be unscrewed and discarded, and before a new injection, put on a new one.
Baeta can be combined with other hypoglycemic drugs. If the drug is combined with sulfonylureas (maninil, diabeton, etc.), then their dose should be reduced to avoid the development of hypoglycemia. There is a separate article about hypoglycemia, so I recommend that you follow the link and study it if you haven’t done so yet. If Baeta is used in conjunction with Metformin, the dose of Metformin does not change, since hypoglycemia is unlikely in this case.
treatment of diabetavictosis is also available in syringe pens at a dose of 6 mg in 1 ml. The volume of the pen is 3 ml. Sold for 1, 2 or 3 syringe pens in a package. Storing and using a syringe pen is similar to a diet. Treatment of diabetes with Victoza is carried out 1 time a day at the same time, which the patient can choose, regardless of food intake. The drug is administered subcutaneously in the thigh, abdomen or shoulder. It can also not be used for intramuscular or intravenous administration.
The initial dose of Victose is 0.6 mg per day. After 1 week, you can gradually increase the dose to 1.2 mg. The maximum dose is 1.8 mg, which can be started 1 week after increasing the dose to 1.2 mg. Above this dose, the drug is not recommended. By analogy with Bayou, Victoza can be used with other antidiabetic drugs.
And now about the most important thing-the price and availability of both drugs. This group of drugs is not included in either the Federal or regional list of preferential medicines for the treatment of patients with diabetes. Therefore, these drugs will have to be purchased with your own money. To be honest, these drugs are not cheap. The price depends on the dose of the medicine administered and on the packaging. For example, a 1.2 mg Diet contains 60 doses of the drug. This amount is enough for 1 month. provided that the prescribed daily dose is 5 mcg. In this case, the drug will cost you an average of 4,600 rubles per month. If this is Victoza, then with a minimum daily dose of 6 mg, the drug will cost 3,400 rubles per month.
DPP-4 inhibitors in the treatment of type 2 diabetes
As I mentioned above, the enzyme dipeptidyl peptidase-4 (DPP-4) destroys incretin hormones. Therefore, scientists decided to block this enzyme, as a result of which they prolonged the physiological effect of their own hormones. A big advantage of this group of drugs is an increase in both hormones-GPP-1 and GIP, which increases the effect of the drug. Also positive is the fact that the increase in these hormones occurs in the physiological range of no more than 2 times, which completely eliminates the occurrence of hypoglycemic reactions.
A plus can also be considered the method of administration of these drugs-these are tablet drugs, not injections. There are practically no side effects of DPP-4 inhibitors, since hormones increase within physiological limits, as if it were in a healthy person. When using inhibitors, the level of glycated hemoglobin decreases by 0.5-1.8 %. But these drugs have almost no effect on body weight.
Today in the Russian market there are three drug Galvus (vildagliptin), Januvia (sitagliptin), Onglyza (saxagliptin).
Januvia is the very first drug from this group, which began to be used first in the United States, and then around the world. This drug can be used both in monotherapy and in combination with other hypoglycemic drugs and even insulin. Januvia blocks the enzyme for 24 hours, begins to act within 30 minutes after ingestion.
Available in tablets in dosages of 25, 50 and 100 mg. The recommended dose is 100 mg per day (1 time per day), can be taken regardless of food intake. In case of renal insufficiency, the dose of the drug is reduced to 25 or 50 mg.
The effect of the application can be seen already in the first month of use, both lean and postprandial blood glucose levels are reduced.
For the convenience of combination therapy to Januvia produced in the form of a combination drug with Metformin — Janumet. Available in two doses: 50 mg of Januvia + 500 mg of Metformin and 50 mg of Januvia + 1000 mg of Metformin. In this form, tablets are taken 2 times a day.
treatment of diabetagalvus is also a representative of the group of DPP-4 inhibitors. It is taken regardless of food intake. The initial dose of Galvus is 50 mg once a day, if necessary, the dose is increased to 100 mg, but the reception is distributed at 50 mg 2 times a day.
Galvus is also used in combination with other hypoglycemic drugs. Therefore, there is such a combined drug as Galvusmet, which also has Metformin in its composition. There are tablets with 500, 850 and 1000 mg of Metformin, while the dose of Galvus remains 50 mg.
As a rule, a combination of drugs is prescribed if monotherapy is ineffective. In the case of Galvusmet, the drug is taken 2 times a day. In combination with other medications, Galvus is taken only once a day.
With mild renal impairment, the dose of the drug can not be changed. When comparing two preparations of Januvia and Galvus, identical changes in glycated hemoglobin, postprandial glycemia (sugar after meals) and fasting glycemia were observed.
treatment of diabetaonglysis is the last open drug of the DPP-4 inhibitor group. The drug is available in tablets of 2.5 and 5 mg. It is taken regardless of food intake 1 time a day. It is also used both as monotherapy and in combination with other hypoglycemic drugs. But there is no combination drug with Metformin yet, as is the case with Januvia or Galvus.
In mild renal insufficiency, dose adjustment is not required, in the middle and severe stages, the dose of the drug is reduced by 2 times. When compared with Januvia and Galvus, there were also no obvious and significant differences either in effectiveness or in the frequency of side effects. Therefore, the choice of the drug depends on the price and experience of the doctor with this drug.
Unfortunately, these medicines are not included in the Federal list of preferential medicines, but in some regions it is possible to extract these medicines from the regional register at the expense of the local budget. So, again, you have to buy these drugs with your own money.
The price of these drugs also does not differ much. For example, you will need to spend an average of 2,200-2,400 rubles to treat diabetes with Januvia at a dose of 100 mg. And Galvus in a dose of 50 mg will cost you 800-900 rubles a month. Onglyza 5 mg costs 1,700 rubles a month. Prices are purely approximate, I took them from online stores.
Who are these groups of drugs prescribed to? Drugs from these two groups can be prescribed already during the onset of the disease, for those who can afford it, of course. It is especially important at this time to maintain, and perhaps even increase the pool of beta cells of the pancreas, then diabetes will be well compensated for a long time and will not require the appointment of insulin.
How many medications are prescribed at the same time when diabetes is detected depends on the level of glycated hemoglobin.
That’s it for me. It turned out a lot, I don’t even know if you can handle it. But I know that there are people among the readers who are already receiving these drugs. Therefore, I am asking you to share your impressions about the medicine. I think it will be useful to know this for those who are still thinking about switching to a new treatment or not.
And remember that despite the most effective medications, the normalization of nutrition in diabetes plays a leading role together with regular physical activity.
Do you want to know more about the treatment of type 2 diabetes, what groups of medications exist, in which cases they are prescribed, and also more about insulin for diabetics with type 2? Then you will benefit from my 4-hour video lecture on the topic of medicinal treatment of diabetes. Read more about this lecture on a separate page.