Thiazolidinediones: Hypoglycemic agents that improve insulin resistance

Thiazolidinediones

What are thiazolidinediones (TG-10) hypoglycemic drugs?

Thiazolidinediones (also known as glitazones) are hypoglycemic drugs, primarily referring to insulin sensitizers. They are a class of novel oral hypoglycemic drugs developed in the early 1980s that enhance insulin sensitivity. Their effects are as follows:

① Improve glucose metabolism: Because these drugs can reduce insulin resistance and enhance insulin action, they are called insulin sensitizers. These drugs mainly act on insulin target tissues (such as fat, muscle, and liver), increasing glucose oxidation and fat synthesis in adipose tissue, and increasing glucose uptake and oxidation in muscle tissue, thereby lowering blood glucose. Additionally, they can increase liver glycogen synthesis, decrease gluconeogenesis, and decrease liver glycogen output, thus lowering blood glucose.

② Improve lipid metabolism: Thiazolidinediones can significantly reduce triglyceride and free fatty acid levels, decrease low-density lipoprotein cholesterol, and increase high-density lipoprotein cholesterol.

③ Enhance insulin action and protect pancreatic β-cells. Therefore, insulin sensitizers are currently the only drugs that can treat the underlying cause of type 2 diabetes. Insulin sensitizers include rosiglitazone (Avandia) and pioglitazone, with rosiglitazone being the most commonly used first-line drug for treating type 2 diabetes.

What are some commonly used thiazolidinedione drugs? What are their characteristics and dosages?

①Rosiglitazone (Avandia): This is the second thiazolidinedione insulin sensitizer approved for marketing. It increases the sensitivity of target organs such as the liver, bones, and adipose tissue to insulin, significantly reducing fasting blood glucose, postprandial blood glucose, and glycated hemoglobin levels. However, this class of drugs is only suitable for type 2 diabetes patients who still have some insulin secretion capacity; it is ineffective for those with complete loss of pancreatic function. This class of drugs has a different mechanism of action than insulin, sulfonylureas, and biguanides, but they have a synergistic effect when used in combination and can reduce insulin dosage (by 4.8–9.4 U per day). While lowering triglyceride levels, this product can increase high-density lipoprotein cholesterol levels, reducing the risk of cardiovascular disease. It is well-tolerated by patients over 65 years of age. It rarely causes hypoglycemia during treatment. The American Association of Clinical Endocrinologists states that this class of drugs should be comprehensively evaluated from both benefit and risk perspectives. Cases of liver failure and hepatocellular damage have been observed in clinical use, but this class of drugs has unique advantages in improving insulin resistance in the vast majority of patients with type 2 diabetes. Compared comprehensively with insulin, sulfonylureas, and biguanides, this class of drugs has a comparable safety profile, is safer and more reliable than a placebo, and can delay the need for insulin injections. The recommended oral dose is 4 mg once daily between meals; or 2 mg twice daily with food. If the therapeutic effect is unsatisfactory after 12 weeks of treatment, the dose can be increased to 8 mg once daily, or 2-4 mg twice daily.

② Pioglitazone (Aitine): This is the third thiazolidinedione insulin sensitizer approved by the US Food and Drug Administration in July 1999. Its application range is wider than rosiglitazone, and its efficacy is better. In addition to reducing glycogen synthesis and increasing glycolysis, it can significantly reduce triglyceride and very low LDL cholesterol levels in obese patients, with no significant hepatotoxicity observed. It is used for type 2 diabetes, either alone or in combination with sulfonylureas or biguanides. Oral administration: 15 mg or 30 mg three times daily. 53. Why is early use of thiazolidinediones (TLIs) recommended? TLIs have demonstrated significant clinical efficacy, effectively lowering fasting blood glucose by 3.3–4.5 mmol/L and glycated hemoglobin (HbA1c) by 1.4%–2.6%. Combining them with other hypoglycemic agents enhances their effect; even in insulin-injecting type 2 diabetes patients, TLIs significantly improve glycemic control. Furthermore, they regulate lipid disorders, thus reducing cardiovascular risk factors and slowing disease progression. Therefore, in clinical treatment, obese or overweight type 2 diabetes patients should be given priority and given TLIs as early as possible. Early use of these drugs not only means a decrease and achievement of target levels for blood glucose, HbA1c, and lipids, but more importantly, their potential benefits lie in protecting and improving pancreatic beta cell function, thereby slowing disease progression, improving many cardiovascular risk factors, preventing chronic complications and cardiovascular events, improving quality of life, and reducing disability and mortality rates.

Which diabetic patients are suitable for thiazolidinedione (Thiazolidinedione) hypoglycemic agents?

① Patients with prediabetes (impaired glucose tolerance) to prevent and stop diabetic complications. After using thiazolidinediones, 80% of patients can reverse the progression of the disease, while effectively reducing cardiovascular complications.

② Obese patients and those with hypertension, hyperlipidemia, and hyperglycemia ("three highs"), especially those with existing insulin resistance, are particularly suitable for this class of drugs. It is the first choice for diabetic patients with cardiovascular complications.

③ Patients whose diabetes is not well controlled by diet and exercise.

④ Patients whose blood sugar cannot be controlled by metformin alone.

⑤ Patients whose blood sugar is not well controlled by insulin alone.

Which diabetic patients are not suitable for thiazolidinedione (Thiazolidinedione) hypoglycemic agents?

① Patients with known hypersensitivity to this product or any of its components.

② Patients with diabetic ketoacidosis.

③ Patients with type 1 diabetes.

④ Patients with edema.

⑤ Not suitable for patients with grade 3 or 4 cardiac dysfunction.

⑥ Patients with active liver disease or serum alanine aminotransferase levels 2.5 to 3 times higher than the upper limit of normal.

⑦ Not recommended for patients under 18 years of age.

⑧ Not recommended for pregnant or breastfeeding women.

What are the adverse reactions of thiazolidinediones?

① Hematologic system: Anemia may occur, especially when used in combination with metformin, which has a higher incidence than when used alone or in combination with sulfonylureas.

② Cardiovascular system: Fluid retention may occur, thereby aggravating heart failure; there have been reports of myocardial infarction.

③ Metabolic-endocrine disorders: Weight gain may occur, the mechanism of which is unclear.

④ Digestive system: Elevated alanine aminotransferase (ALT) may occur; loss of appetite, abdominal pain, nausea, and vomiting are rare.

⑤ Other: Edema and back pain may occur.

What precautions should be taken when using thiazolidinediones?

① Thiazolidinediones only work in the presence of endogenous insulin; therefore, patients with type 1 diabetes should not use this class of drugs.

② Liver function must be routinely tested before medication; it is not suitable for patients with liver disease or impaired liver function. ③ Liver function should be monitored during medication. This medication should not be used if alanine aminotransferase (ALT) exceeds 2.5 times the upper limit of normal. In particular, medication must be discontinued if ALT exceeds 3 times the normal limit.

④ Thiazolidinediones increase tissue sensitivity to insulin, reduce insulin resistance, and protect pancreatic function; therefore, they should be used as early as possible.

⑤ This class of drugs does not cause hypoglycemia when used alone. However, there is a risk of hypoglycemia when used in combination with other oral hypoglycemic agents. The dosage of the combined medication should be adjusted according to the patient's blood glucose levels.

⑥ No dosage adjustment is required for patients with renal impairment when using this product alone. Because metformin is contraindicated in patients with renal impairment, this product should not be used in combination with metformin in such patients.