Exenatide is better than placebo in type 2 diabetes not on insulin at a cost

The spread of type 2 diabetes mellitus (DM 2) has become an epidemic. Currently, there are already 8 different types of hypoglycemic drugs (SSPS) to maintain normal blood glucose.

But the reluctance of diabetics to change their lifestyle and strictly adhere to the prescribed treatment strategy leads to the aggravation of pathology and the development of characteristic comorbidities. Often, combined treatment with a double or even triple SSP regimen is not enough, and insulin therapy for DM 2 becomes unavoidable.

The information, photos and videos in this article are an overview of the recommendations that were given in 2018 to practicing endocrinologists by specialists from the American diabetes Association (ADA) and the European Association for the study of diabetes mellitus (EASD).

Initiation of insulin therapy for DM 2

The beginning of treatment with insulin injections occurs if:

  • treatment with a combination of SSP did not allow achieving the target level of glycemia;
  • the patient’s quality of life has deteriorated;
  • there is a clear trend of progression of chronic heart failure and kidney disease;
  • monotherapy AGPP-1 (active substance-liraglutide, trade name-Victoza) did not give the proper effect or is not available due to the high price of the drug;
  • periodically, there are manifestations of metabolic decompensation-ketoacidosis (acetone in the blood), glucosuria (sugar in the urine), shock States and hyperglycemic comas;
  • HbA1c values exceed 10% or 2% above the individual target blood glucose level.

Initiation of insulin therapy is recommended to be performed using one of the basal insulin preparations. It powerfully suppresses the synthesis of glucose from non-carbohydrate products in the liver. This will help lower your fasting blood sugar level, which in turn will positively affect your glycemic level throughout the day.
Insulin glargine-300 – the # 1 choice for patients with type 2 diabetes with obesity

Today, all existing varieties of basal insulin preparations are presented in pharmacies in Russia: ultrashort and short insulins, neutral Protamine Hagedorn (isofan), long-acting and ultra-long-acting insulins. The ADA / EASD recommends starting with long-acting insulin injections. They, with the correct dosage, allow you to avoid the development of hypoglycemia, especially in diabetics with concomitant cardiovascular diseases.

On a note. It is proved that the frequency of hypoglycemic attacks is lower in those diabetics who are treated with glargine-300 instead of glargine-100.

One of the important conditions for the success of achieving the norm of glucose in the blood after the start of treatment with basal insulin is titration (individual selection) of its dose. However, all previous appointments are not canceled. The combined intake of SSP, diet and physical therapy continues.

To select the optimal effective dose of glargine-300 patients are offered to act according to the following algorithm:

The initial dose for diabetics with normal body weight or a slight excess (up to 5 kg) is 10 IU. For obese patients, the dose is calculated as 0.1-0.2 IU per 1 kg of body weight.
Every 3 days, in the morning of 4 days, the dose increases by 2 IU. Such periodic increase continues until, until the blood glucose levels will not reach the desired target. The doctor determines its value for each patient individually. To do this, various indicators are analyzed, including the level of glycated hemoglobin (HbA1c).
If an attack of hypoglycemia occurs during the titration period, the patient should analyze what errors in food or physical behavior could cause this condition, and prevent them in the next 2 days. If this does not help or the reason is not found, then the amount of the achieved dose should be reduced by 15%.

Adding ultra-long basal insulin injections to the treatment regimen for DM 2 helps, but unfortunately not everyone. Those who have been treated for a long time with a combination of 2 or 3 SSPS, have a large excess weight and/or too high HbA1c indicators, almost 100% will need a rapid increase in therapy.

Intensification of insulin treatment

If adequate titration of basal long – acting insulin, even when reaching the norm of fasting blood glucose, did not lead to a targeted reduction in glycated hemoglobin, as well as in the case when the total dose of glargine exceeds the dose of 0.7-1.0 IU per kg of body weight, then ADA/EASD experts recommend adding prandial (ultrashort) insulin injections to the treatment regimen.
Active substances analogs of human prandial insulin duration of action

Ultra-short versions of drugs are not only faster, but also allow you to safely make injections with a large dosage, and treatment with them significantly reduces the risk of developing hypoglycemic conditions after eating or during sleep.

Basal Mode +»

Before completely switching to basic bolus insulin treatment, ADA/EASD experts suggest trying the “basal +” treatment plan. In addition to diet, exercise, 2-or 3-component SSP therapy, and insulin glargine injections, his Protocol includes an injection of ultrashort insulin.

It should be done on the eve of lunch, or before the meal, after which the highest increase in the concentration of glucose in the blood is recorded.
Apidra Solo Star is manufactured by Sanofi Aventis (Deutschland, GmbH)

If possible, it is better to inject insulin glulisin. Only one company produces it. The trade name and type of packaging for Russia are shown in the photo above. The price of this drug is slightly higher than that of its analogues.

But in contrast to the same ultrashort insulins-lispro and aspart:

Glulisin has a fundamentally different structure of molecules (see the fragment in the upper-left corner of the photo) and does not contain Zn2+. This ensures its faster absorption, the beginning of action and reaching peak efficiency.
The drug can be injected as 15 minutes before a meal, or just before a meal. This is an important advantage, since such forgetfulness is extremely common in all diabetics. Even the most disciplined patients make mistakes.
The rate of dissociation in subcutaneous fat, the beginning and end of the action of this hormone does not depend on the human body mass index.

Into consideration. The safety and clinical efficacy of the “basal +” scheme was proven by Proof-of-Concept (Owens et al.) and OPAL (Lankish et al.) studies. a Decrease in HbA1c to<7.0% occurred in 24 weeks in 73% of the subjects.

Glulisin titration

To correctly select the dose of Apidra Solostar injection, it is suggested not to calculate it every time, based on the amount of carbohydrates planned to be eaten (in Bread Units).
With DM 2, it is recommended to adhere to a low-carb eating pattern

If a diabetic follows a diet, then it is enough to act according to this scheme:

  • start for patients with normal body weight or +5 kg – 4 IU, and the initial dose for obese patients-10% of the dose of glargine-300;
  • increasing the dose to reach the target level of glycemia is performed every 3 days, by 1-2 IU or 10-15%, respectively;
  • if hypoglycemic conditions occur, it is necessary to find out and eliminate the cause, and if it is not found, then reduce the dose by 2-4 IU or 10-20%.

Attention. If HbA1c ⩽is reduced by 8.0%, the dose of glulisin should be immediately reduced by 4 IU or 10%.

If after 14 weeks there is no clear tendency to decrease the glycated globin index, then according to the ADA/EASD instructions, you should add an injection of ultrashort insulin before dinner, and if this does not lead to normalization of HbA1c, then after another 3 months, glulisin is taken and the third time a day – before Breakfast.

This algorithm, in comparison with the abrupt transition to a basic-bolus treatment Protocol, has been proven to reduce the risk of hypoglycemia and, importantly, does not cause weight gain, as well as improves the quality of life of a diabetic, his satisfaction and commitment to this therapy scheme.

At the end of the article, we offer to watch a video that contains detailed information about the most prolonged insulin preparation Tresiba (the active substance is insulin degludek). If possible, in the proposed treatment regimen for DM 2, it can be replaced with Tujeo injections (insulin glargine, 300 IU).

Douglas Badenoch
I am an information scientist with an interest in making knowledge from systematic research more accessible to people who need it. This means you. I've been attempting this in the area of Evidence-Based Health Care since 1995. So far the results have been mixed. For some reason we expected busy clinicians to search databases and appraise papers instead of seeing patients. We also expected publishers to make the research freely available to the people who paid for it.. Ha! Hence The National Elf service.

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