Oral antidiabetic drugs
Oral antidiabetic drugs
Many types of oral antidiabetic drugs are approved for use in the United States. Types of available oral antidiabetic drugs include:
- first-generation sulfonylureas, which include acetohexamide, chlorpropamide, tolazamide, and tolbutamide
- second-generation sulfonylureas, which include gliclazide, glipizide, glimepiride, and glyburide.
- thiazolidinediones, which include pioglitazone and rosiglitazone
- a biguanide drug, metformin
- alpha-glucosidase inhibitors, which include acarbose and miglitol
- a meglitinide drug, repaglinide
- an amino acid derivative, nateglinide
- combination therapies, which include glipizide and metformin, glyburide and metformin, and rosiglitazone and metformin.
Pharmacokinetics
Oral antidiabetic drugs are well absorbed from the GI tract and distributed via the bloodstream throughout the body. Because repaglinide has a short duration of action, it’s given before meals.
Metabolism and excretion
Oral antidiabetic drugs are metabolized primarily in the liver and are excreted mostly in urine, with some excreted in bile. Glyburide is excreted equally in urine and stool; rosiglitazone and pioglitazone are largely excreted in both.
Pharmacodynamics
It’s believed that oral antidiabetic drugs produce actions both within and outside the pancreas (extrapancreatic) to regulate blood glucose.
Pancreas partners
Oral antidiabetic drugs probably stimulate pancreatic beta cells to release insulin in a patient with a minimally functioning pancreas. Within a few weeks to a few months of starting sulfonylureas, pancreatic insulin secretion drops to pretreatment levels, but blood glucose levels remain normal or near-normal. Most likely, it’s the actions of the oral antidiabetic agents outside of the pancreas that maintain this glucose control.
Working beyond the pancreas
Oral antidiabetic drugs provide several extrapancreatic actions to decrease and control blood glucose. They can go to work in the liver and decrease glucose production (gluconeogenesis) there. Also, by increasing the number of insulin receptors in the peripheral tissues, they provide more opportunities for the cells to bind sufficiently with insulin, initiating the process of glucose metabolism.
Getting in on the action
Other oral antidiabetic agents produce specific actions:
- Pioglitazone and rosiglitazone improve insulin sensitivity and lower glucose production by the liver.
- Metformin decreases liver production and intestinal absorption of glucose and improves insulin sensitivity.
- Acarbose and miglitol inhibit enzymes, delaying glucose absorption.
- Repaglinide and nateglinide increase insulin secretion.
Pharmacotherapeutics
Oral antidiabetic drugs are indicated for patients with type 2 diabetes if diet and exercise can’t control blood glucose levels. These drugs aren’t effective in patients with type 1 diabetes because the patients’ pancreatic beta cells aren’t functioning at a minimal level.
The old 1-2 punch
Combinations of multiple oral antidiabetic drugs or an oral antidiabetic drug with insulin therapy may be indicated for some patients who don’t respond to either therapy alone.
Drug interactions
Hypoglycemia and hyperglycemia are the main risks when oral antidiabetic drugs interact with other drugs.
Getting too low
Hypoglycemia may occur when sulfonylureas are combined with alcohol, anabolic steroids, chloramphenicol, cimetidine, clofibrate, coumadin, fluconazole, gemfibrozil, MAOIs, phenylbutazone, ranitidine, salicylates, or sulfonamides. It may also occur when metformin is combined with cimetidine, nifedipine, procainamide, ranitidine, or vancomycin. Hypoglycemia is less likely to occur when metformin is used as a single agent.
Cautionary tales
To maintain blood glucose levels as close to normal as possible, pregnant women should avoid oral antidiabetic agents. Insulin therapy is recommended instead.
Because aging is commonly associated with a decline in kidney function, and because the kidneys substantially excrete metformin, metformin should be used with caution in elderly patients. Patients with renal and hepatic impairment should also avoid metformin.
Going too high
Hyperglycemia may occur when sulfonylureas are taken with corticosteroids, dextrothyroxine, rifampin, sympathomimetics, and thiazide diuretics.
Because metformin given with iodinated contrast dyes can cause acute renal failure, metformin doses should be withheld in patients undergoing procedures that require I.V. contrast dye and
not restarted for at least 48 hours after the procedure.
not restarted for at least 48 hours after the procedure.
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