Sulfonylurea oral hypoglycemic drug treatment failure

Sulfonylurea oral hypoglycemic drug treatment failure:

Sulfonylurea oral hypoglycemic drug failure refers to the absence of good treatment effects in diabetic patients despite adequate and correct use of a certain sulfonylurea drug for a sufficient period of time. Regarding the interpretation of “adequate,” different scholars have different understandings, but it is generally believed that no matter what kind of sulfonylurea drug, it should not exceed 6 tablets per day, such as 15mg of Glibenclamide, 30mg of Meglitinide, 180mg of Glyburide, 320mg of Diamicron, and 3g of Methylphenidate, etc.

Regarding the “sufficient period of time,” it is generally advocated to use a 3-month period, with at least 1 month being the minimum. Regarding “good treatment effects,” there are different standards worldwide, and diabetic control indicators can be referred to for reference. If the control is poor, it indicates drug treatment failure. Sulfonylurea drug failure can be divided into two categories:

(1) Primary Sulfonylurea Drug Treatment Failure: This refers to diabetic patients who have never used sulfonylurea drugs before, have taken adequate doses for more than a month, but show no significant efficacy, with no decrease or minimal decrease in blood sugar. This situation is very rare and seldom seen in patients.

(2) Secondary Sulfonylurea Drug Treatment Failure: This refers to patients who have previously used a certain sulfonylurea drug effectively for 3 months or longer but suddenly or gradually become ineffective or have poor efficacy later, with the failure lasting for more than 1 month. Common sulfonylurea drug failures belong to this category. It is worth emphasizing that the so-called secondary failure commonly seen is mostly not true failure, but rather poor efficacy caused by various reasons. Therefore, both doctors and patients should correctly understand sulfonylurea drug failure.

Only after excluding other possible factors that affect treatment efficacy can sulfonylurea drug treatment failure be considered. Other common reasons for poor efficacy include inappropriate case selection, such as using sulfonylurea drugs alone for type 1 diabetes, lax diet control, lack of physical activity, poor insulin response to sulfonylurea stimulation, which is the most common reason, relaxation of treatment, achieving efficacy after treatment but not adhering to doctor’s orders, and drug quality issues, such as expired medications.

The exact mechanism of sulfonylurea failure is not clear, but it is mainly related to the following factors:

1. Sulfonylurea drug absorption disorders: Long-term high blood sugar can cause delayed gastric emptying, slow absorption of sulfonylurea, and failure to reach the effective blood concentration for stimulating insulin secretion.
2. Reduction in the number of islet β cells: Such as patients actually having slowly progressive type 1 diabetes.
3. Decreased sulfonylurea receptor number and affinity on β cells: Long-term use of large doses of sulfonylurea can lead to islet β cell failure and decreased sensitivity.
4. Insulin resistance: Although the islet β cells can secrete sufficient insulin, the body’s response to insulin is reduced due to the presence of insulin antibodies or receptor and receptor posterior disorders.

To treat and prevent sulfonylurea failure, the following measures should be taken: patients should follow their doctor’s guidance:

1. Review the indications, exclude type 1 diabetes, and for obese patients with insulin resistance, use biguanides first to improve insulin sensitivity.
2. Improve diet and exercise therapy, correct incorrect lifestyle, and lose weight first for obese patients.
3. Take sulfonylureas correctly, take medication 15-30 minutes before meals, and use them regularly.
4. Switch to other types of sulfonylureas.Changing medication may lead to therapeutic effects．
5. Some recommend combining two sulfonylureas, but since the receptors are common and are voltage-dependent potassium channel inhibitors, the combined effect needs to be evaluated.
6. Add biguanides.
7. Add insulin.
8. Add other types of hypoglycemic drugs, such as Alogliptin．