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Oral Antidiabetic Medication – Classes, Mechanism Of Action And Side Effects

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Oral Antidiabetic Medication

Oral antidiabetic medication includes a multitude of substances, grouped as follows: sulfonylureas, biguanides, meglitinides, thiazolidinediones, alpha-glucosidase inhibitors and new antidiabetic drugs.

The main indications of oral antidiabetic medication include: type 2 diabetes mellitus, which is not regulated only with properly prescribed and rigorously observed diet.

Contraindications of oral antidiabetic medication:

  1. Diabetic ketoacidosis;
  2. Type 1 diabetes mellitus;
  3. Associated infections;
  4. Pregnancy, because oral antidiabetic medication have teratogenic effect;
  5. Before, during and after surgical interventions (until the recovery);
  6. Type 2 diabetes mellitus, which can be balanced with diet, but because the patient is undisciplined, this goal can not be achieved (the medication does not improve glucose balance).
Type 2 diabetes

Type 2 diabetes

Classification of oral antidiabetic medication:

  • Sulfonylureas:
  1. Generation I: Tolbutamide, Chlorpropamide, Tolazamide.
  2. Generation II: Glibenclamide, Glipizide, Gliclazide, Gliquidone.
  3. Generation III: Glimepiride.
  • Biguanides: Metformin, Buformin.
  • Thiazolidinediones: Pioglitazone, Rosiglitazone.
  • Meglitinides: Repaglinide, Nateglinide.
  • Alpha glucosidase inhibitors: Acarbose, Miglitol, Voglibose.
  • New antidiabetic drugs: Exenatide (Byetta), Sitagliptin (Januvia).
  • Combinations: Glibomet (metformin + glibenclamide), Avandamet (rosiglitazone + metformin), Competact (pioglitazone + metformin), Janumet (sitagliptin + metformin).


Sulphonylurea drugs used by almost half a century, to treat type 2 diabetes, are indicate in normal weight patients who have type 2 diabetes and in obese patients if they can not tolerate metformin.

After ingestion, sulphonylurea drugs are rapidly absorbed in the intestine, pass into the bloodstream, where they bind to specific proteins (albumin, in particular) and reach the liver where they are metabolized into inactive byproducts. Elimination is predominantly renal, with the exception of gliquidone that is eliminated in the bile in proportion of 95%.

Mechanism of action. Sulphonylureas are fixing on specific receptors and acts through the potassium channel from the pancreatic and the extra-pancreatic level. At pancreatic level, increase insulin secretion and at the level of pancreatic beta cells, they increase the number of insulin receptors. At extra-pancreatic sulphonylurea drugs decrease hepatic gluconeogenesis (glucose synthesis from non-carbohydrate sources), increased glycolysis and enhances insulin action in skeletal muscle and in adipose tissue.

Adverse effects. The main side effect of sulphonylureas is hypoglycaemia (favored by a high dose, kidney failure, liver failure, alcohol consumption, intense physical effort, age over 70 years). Other adverse effects consist of digestive manifestations (nausea, epigastric pain, liver pain) and of haematological manifestations (pancytopenia, autoimmune hemolytic anemia, thrombocytopenia).

Sulphonylureas can not be associate with each other, but may be associated with biguanides, thiazolidinediones, and even with insulin therapy.




Biguanides are used to treat type 2 diabetes with obesity. The most used drug in this class is metformin.

After ingestion, metformin is absorbed at intestinal level, disseminate in the body and is excreted in urine and faeces, unchanged.

Mechanism of action. Biguanides increase insulin action by binding to specific receptors, decrease intestinal absorption of carbohydrates and decrease anaerobic gluconeogenesis.

Adverse effects. Digestive manifestations, especially epigastric pain and diarrhea, occur in approximately 20% of cases and it is requiring a dose reduction or even quitting to this class of oral antidiabetic medication. Lactic acidosis is another adverse effect.

Biguanides may be associated with sulphonylureas, with thiazolidinediones and with insulin in both type 2 and type 1 diabetes.




Thiazolidinediones have been introduced in the treatment of type 2 diabetes in 1999.

Mechanism of action. Thiazolidinediones lower blood glucose levels by reducing insulinresistance in adipose tissue, in the muscle and in the liver, thus increasing insulin sensitivity, in this way it favors the hypoglycemic action of insulin.

Adverse effects. Before and during treatment with thiazolidinediones, is necessary to control liver enzymes (AST, ALT in particular). This class of oral antidiabetic medication is well tolerated in general, however, sometimes may occur mild edema of the lower limbs, through the loss of elimination of salt and water, which, on the one hand, may decrease hemoglobin, with the appearance of anemia, and on the other hand, requires to be administered with caution to patients with type 2 diabetes and heart failure. Thiazolidinediones can cause hypercholesterolemia and triglycerides disorders and for this reason, blood fats should be checked periodically.

The two used thiazolidinediones are pioglitazone and rosiglitazone, the latter being less used these days, because it is considered that increase the risk of cardiovascular complications.




After oral administration, meglitinides are absorbed at intestinal level, are metabolized in the liver and will result inactive byproducts, which are excreted into the bile.

Mechanism of action. This drugs are fixing on specific sites of potassium channels and increase insulin secretion stimulated by glucose level if there is a residual function of pancreatic beta cells.

Adverse effects. Rarely can cause hypoglycemia.

Considering that this class of oral antidiabetic medication has a short half-life, meglitinides are useful in correcting postprandial hyperglycemia. The tablets of this class are given after every meal (“one meal-one dose”).

Alpha glucosidase inhibitors:

Alpha glucosidase inhibitors are used to treat type 2 diabetes, which is inadequately controlled by diet.

Mechanism of action. Alpha glucosidase inhibitors are reversibly binding to alpha-glucosidase enzymes of small intestine cells, enzymes that are designed to split disaccharides and oligosaccharides, thus preventing the digestion and absorption of carbohydrates, along the small intestine. Thus, carbohydrates reach into the colon and are metabolized by bacteria, found at this level, in short-chain fatty acids and then are eliminated.

Adverse effects. Alpha glucosidase inhibitors can cause a slight weight gain, abdominal bloating, flatulence, abdominal discomfort, diarrhea, and rarely can cause liver test abnormalities.



New antidiabetic drugs:

  1. Byetta (exenatide) is a synthetic analogue of GLP-1. GLP-1 is a substance secreted by the body that stimulates insulin secretion, but has other beneficial effects such as delayed passage of food from the stomach into the small intestine and stimulating satiety. The administration of this drug is by subcutaneous injection, like insulin, in a fixed dose, 2 times a day with pre-filled pen, initially every 5 micrograms twice a day, then 10 micrograms twice a day. Possible side effects include nausea, vomiting and rarely hypoglycemia.
  2. Januvia (sitagliptin), a drug that inhibits the destruction of GLP-1 blood levels, so will extended the action of GLP-1 and will increase the insulin secretion. Daily dose is 100 mg. This drug is used in combinations with metformin.