Nashville Diabetes Dentist

Anti-diabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.

Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected or inhaled.

Diabetes mellitus type 2 is a disease of insulin resistance by cells. Treatments include (1) agents which increase the amount of insulin secreted by the pancreas, (2) agents which increase the sensitivity of target organs to insulin, and (3) agents which decrease the rate at which glucose is absorbed from the gastrointestinal tract.

Several groups of drugs, mostly given by mouth, are effective in Type II, often in combination. The therapeutic combination in Type II may include insulin, not necessarily because oral agents have failed completely, but in search of a desired combination of effects. The great advantage of injected insulin in Type II is that a well-educated patient can adjust the dose, or even take additional doses, when blood glucose levels measured by the patient, usually with a simple meter, as needed by the measured amount of sugar in the blood.

Insulin

Insulin is usually given subcutaneously, either by injections or by an insulin pump. Research is underway of other routes of administration. In acute care settings, insulin may also be given intravenously. There are several types of insulin, characterized by the rate which they are metabolized by the body.

Secretagogues

Sulfonylureas

Sulfonylureas were the first widely used oral hypoglycemic medications. Sulfonylureas are insulin secretagogues, triggering insulin release by direct action on the K_ATP channel of the pancreatic beta cells. Eight types of these pills have been marketed in North America, but not all remain available. The “second-generation” drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side effects. All may cause weight gain.

Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful in Type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They can not be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side effect is hypoglycemia.

Typical reductions in A1C values for second generation sulfonylureas are 1.0-2.0%.

• First-generation agents
  • tolbutamide (Orinase)
  • acetohexamide (Dymelor)
  • tolazamide (Tolinase)
  • chlorpropamide (Diabinese)
• Second-generation agents
  • glipizide (Glucotrol)
  • glyburide (Diabeta, Micronase, Glynase)
  • glimepiride (Amaryl)
  • gliclazide (Diamicron)

Meglitinides

Meglitinides help the pancreas produce insulin and are often called “short-acting secretagogues.” Their mode of action is original, affecting potassium channels. By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, hence enhancing insulin secretion.

They are taken with or shortly before meals to boost the insulin response to each meal. If a meal is skipped, the medication is also skipped.

Typical reductions in A1C values are 0.5-1.0%.

• repaglinide (Prandin)
• nateglinide (Starlix)

Adverse reactions include weight gain and hypoglycemia.

Sensitizers

Insulin sensitizeres address the core problem in Type II diabetes—insulin resistance. Among oral hypoglycemic agents, insulin sensitizers are the largest category.

Biguanides

Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin, a biguanide, has become the most commonly used agent for type 2 diabetes in children and teenagers. Amongst common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain.

Typical reductions in A1C values for metformin is 1.5-2.0%.

• metformin (Glucophage). Metformin may be the best choice for patients who also have heart failure. Should be temporarily discontinued before any radiographic procedure involving intravenous iodinated contrast as patients are at an increased risk of lactic acidosis.
• phenformin (DBI): used from 1960s through 1980s, withdrawn due to lactic acidosis risk.
• buformin: also withdrawn due to lactic acidosis risk

Metformin is usually the first-line medication used for treatment of type-2 diabetes. It is generally prescribed at initial diagnosis in conjunction with exercise and weight loss as opposed to in the past, where Metformin was prescribed after diet and exercise had failed. Initial dosing is 500 mg once daily, then if need be increased to 500 mg twice daily up to 1000 mg twice daily. It is also available in combination with other oral diabetic medications.

There is an extended release formulation available, but it is typically reserved for patients experiencing GI side effects.

Thiazolidinediones

Thiazolidinediones (TZDs), also known as “glitazones,” bind to PPARγ, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on Peroxysome Proliferator Responsive Elements (PPRE). The PPREs influence insulin sensitive genes, which enhance production of mRNAs of insulin dependent enzymes. The final result is better use of glucose by the cells.

Typical reductions in A1C values are 1.5-2.0%.

• rosiglitazone (Avandia)
• pioglitazone (Actos)
• troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk.

As a result of multiple retrospective studies, there is a concern about rosiglitazone’s safety, although it is established that the group, as a whole, has beneficial effects on diabetes. The greatest concern is an increase in the number of severe cardiac events in patients taking it. The ADOPT study showed that initial therapy with drugs of this type may prevent the progression of disease, as did the DREAM trial.

Concerns about the safety of rosiglitazone arose when a retrospective meta-analysis was published in the New England Journal of Medicine. There have been a significant number of publications since then, and a Food and Drug Administration panel voted, with some controversy, 20:3 that available studies “supported a signal of harm,” but voted 22:1 to keep the drug on the market. The meta-analysis was not supported by an interim analysis of the trial designed to evaluate the issue, and several other reports have failed to conclude the controversy. This weak evidence for adverse effects has reduced the use of rosiglitazone, despite its important and sustained effects on glycemic control. Safety studies are continuing.

In contrast, at least one large prospective study, PROactive 05, has shown that pioglitazone may decrease the overall incidence of cardiac events in people with type II diabetes who have already had a heart attack.

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