Drugs affecting the hypoglycemic effect of sulfonylureas and the mechanisms of action and indications of biguanides

Commonly used drugs that can enhance the hypoglycemic effect include: ① Salicylate derivatives, phenylbutazone, indomethacin, sulfonamides, penicillin, dicumarol, and methotrexate. These drugs can competitively displace sulfonylureas at their plasma protein binding sites, increasing the concentration of free sulfonylureas in the plasma and thus enhancing their hypoglycemic effect. These drugs only affect first-generation sulfonylureas; second-generation sulfonylureas are non-ionic and therefore unaffected by these drugs. ② Chloramphenicol and various monoamine oxidase inhibitors can inhibit enzyme systems involved in the inactivation of sulfonylureas in vivo, thereby enhancing their hypoglycemic effect. ③ Aspirin inhibits the excretion of chlorpropamide in urine, thus increasing the level of chlorpropamide in the blood. High doses of aspirin, greater than 4 grams daily, can enhance the hypoglycemic effect of chlorpropamide. Low doses of aspirin have little effect. ④ Guanethidine and indolol can inhibit catecholamines and glucagon from promoting glycogenolysis and gluconeogenesis, thus enhancing the hypoglycemic effect of sulfonylureas. Especially in patients with poor food intake, insufficient liver glycogen reserves, poorly controlled diabetes, strenuous exercise, alcoholism, or chronic malnutrition, indolol can exacerbate the effects of sulfonylureas and mask some symptoms caused by excessive release of catecholamines due to hypoglycemia stimulating the sympathetic nervous system. Therefore, indolol must be used with caution in diabetic patients treated with sulfonylureas or insulin. ⑤ Excessive alcohol consumption. Alcohol depletes liver glycogen reserves and inhibits gluconeogenesis, thus aggravating the hypoglycemic effect of sulfonylureas. ⑥ Other drugs such as androgens, clopidogrel, diisopropylpyridine, sulfadiazine, morphine, isoniazid, and para-aminosalicylic acid sodium also enhance the hypoglycemic effect of sulfonylureas.

Common examples include: ① Glucocorticoids and female contraceptives, which can inhibit insulin receptor sensitivity and counteract the hypoglycemic effect of sulfonylureas. High-dose use of glucocorticoids can impair glucose tolerance or induce diabetes in individuals with a genetic predisposition to diabetes but normal glucose tolerance. ② Thiazide diuretics (such as hydrochlorothiazide), phenytoin sodium, chlorpheniramine, indomethacin, etc., can inhibit the release of insulin from β-cells and counteract the hypoglycemic effect of sulfonylureas. ③ Adrenaline, niacin, glucagon, thyroid hormones, etc., can counteract the hypoglycemic effect of insulin.

(1) Increase insulin-mediated glucose use.

(2) Increase basal glucose utilization.

(3) Reduce liver glucose output.

(4) Reduces intestinal glucose absorption.

(5) Metformin can also lower cholesterol, low-density lipoprotein, triglycerides, and very low-density lipoprotein, and increase high-density lipoprotein.

(6) Inhibits platelet aggregation.

(1) Obese patients with type 2 diabetes.

(2) Individuals whose blood glucose control has not been achieved with sulfonylurea therapy.

(3) It can be used to prevent diabetes patients with impaired glucose tolerance.

(1) Patients with poor liver or kidney function or heart or lung diseases should not use this product.

(2) Contraindicated in various acute attacks of diabetes.

(3) This product is contraindicated in elderly or thin patients.

(4) Contraindicated during pregnancy, surgery, childbirth, and for pregnant women.

(5) Contraindicated in patients with severe chronic gastrointestinal diseases.

(6) It is prohibited for those who are drunk or poisoned by ethanol.

(1) For patients with type 2 diabetes who develop the disease in middle age or older, especially obese patients, this type of drug should be the first choice when the disease cannot be satisfactorily controlled by strict diet and exercise.

(2) When sulfonylurea drugs fail primary or secondary, biguanides can be used instead, or combined with biguanides, which often achieves good results.

(3) When patients undergoing insulin therapy use biguanide drugs in combination, the dosage of insulin can be reduced and blood glucose fluctuations can be reduced, but it cannot completely replace insulin.

(4) Diabetic patients who were previously using low doses of insulin (<20 units/day) and are considering switching to oral hypoglycemic agents, but who have allergic reactions to or are unable to respond to sulfonamides, can use biguanides.

(5) For diabetic patients who are resistant to insulin, adding biguanides can reduce the amount of insulin needed.

(6) It can prevent people with impaired glucose tolerance from developing clinical diabetes.

(7) For overweight patients with type 2 diabetes, using sulfonylurea drugs together can help lower blood sugar, blood lipids and weight.