Analysis of sulfonylureas: Their impact on weight loss in patients with type 2 diabetes and selection guidelines

Sulfonylureas (SU) Drugs

1. Pharmacological Actions
Sulfonylureas are sulfonamide derivatives. Currently, there are more than ten types of sulfonylureas available clinically. Their hypoglycemic mechanism mainly involves stimulating the release of insulin from pancreatic islet cells; some drugs have extrapancreatic effects. Sulfonylureas can enhance the binding of insulin to its receptors, improve glucose utilization, and reduce hepatic glucose output, making them a first-line drug for treating non-obese type 2 diabetes patients. Long-term use of sulfonylureas can cause hyperinsulinemia, hypoglycemia, and obesity. A small number of patients may experience leukopenia and gastrointestinal reactions. They are less commonly used for type 2 diabetes complicated by obesity.

2. Drugs and Hypoglycemic Applications

(1) Tolbutamide (D860) The formulation specification is 500mg/tablet. The initial dose is 500mg three times daily before meals; the dose can be adjusted according to blood glucose levels, with a maximum daily dose of 3000mg. Tolbutamide has a slow, weak, and short-lived hypoglycemic effect. Its plasma half-life is 7 hours, and its hypoglycemic effect lasts only 6-8 hours. Tolbutamide is oxidized in the liver and excreted in the urine; therefore, it should be used with caution in patients with liver disease.

(2) Chlorpropamide (Tesupan) Oral administration: 100mg once daily. Maximum daily dose: 500mg. Chlorpropamide has a long plasma half-life of 24-48 hours and an effect lasting up to 36 hours. After binding to blood proteins, 60% is slowly excreted by the kidneys after 3 days. It is contraindicated in patients over 70 years of age and those with impaired renal function.

(3) Glibenclamide (Euglucon) The initial treatment dose is 2.5mg/day, which can be adjusted according to blood glucose levels. The maximum daily dose is 15mg. It is generally taken once before breakfast. Glibenclamide has a plasma half-life of 15 hours and its hypoglycemic effect lasts for 24 hours, making it the most potent hypoglycemic drug among sulfonylureas. Note that the medication should not be taken in divided doses to avoid nocturnal hypoglycemia. Use with caution in the elderly and those with renal insufficiency.

(4) Gliclazide (Diamicron): The initial dose is 40 mg daily, which can be gradually increased to a maximum daily dose of 320 mg, taken in 2-3 divided doses before meals. Diamicron's blood half-life is 10-12 hours, and its effect lasts for 14 hours. In addition to its hypoglycemic effect, it also inhibits platelet adhesion and aggregation. 70% of its metabolites are excreted through the kidneys; use with caution in those with renal insufficiency and the elderly.

(5) Gliquidone (Glucoside): The formulation is available in 30 mg/tablets. The initial treatment dose is 30 mg daily, which can be gradually increased. The maximum daily dose is 180 mg, taken in 2-3 divided doses before meals. Gliquidone has good control over postprandial hyperglycemia, a short duration of action, and is less likely to cause hypoglycemia. This product is metabolized in the liver, with 95% of its metabolites excreted through bile and feces, and less than 5% excreted through the kidneys. It is the first-line drug for patients with mild to moderate renal insufficiency.

(6) Glipizide (Mepiride): The formulation is 5mg/tablet. The initial treatment dose is 5mg daily, which can be gradually increased thereafter. The maximum daily dose is 30mg, taken in 2-3 divided doses before meals. Mepiride has a plasma half-life of 4 hours and its effects can last for 6-8 hours. It is a short-acting hypoglycemic drug with rapid action, and is particularly effective for postprandial hyperglycemia. Its short half-life makes it relatively safe and suitable for the elderly.

(7) Glipizide controlled-release tablets (Reiton): The formulation is 5mg/tablet. The initial treatment dose is 5mg daily, which can be gradually increased thereafter, with a maximum daily dose of 20mg. It should be taken once daily at the same time, either before or after meals, and should not be chewed. Reiton is a controlled-release formulation. Blood solubility gradually increases 2-3 hours after administration, reaching maximum solubility 6-12 hours later, with minimal fluctuations in blood concentration throughout the day. Blood concentration stabilizes after 5 days of administration. A single oral dose of 5mg can achieve an average blood concentration of over 50ng/ml within 24 hours. This product has no adverse effects on blood lipids or weight and further improves insulin sensitivity compared to traditional sulfonylureas.