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Type 2 diabetes has traditionally been treated in a stepwise manner, starting with lifestyle modifications and exercise. As insulin sensitivity of tissues decreases (insulin resistance), there is a compensatory increase in insulin production, but eventually this becomes inadequate as beta cells start to fail. The treatment of Type 2 diabetes, therefore, progresses from diet, to oral agents, to eventual insulin therapy. This reflects the progression from insulin resistance to beta cell failure.

Oral Medications

There are a variety of oral agents for controlling blood sugar in type 2 diabetes, with several new ones having been developed in the past decade. These agents work by different mechanisms and each has different side effects and risk profiles. The choice of agent depends largely on the individual's glycemic control and the presence of other medical conditions that may be contraindications to specific agents. Oral antidiabetic agents are most often used to treat type 2 diabetes when lifestyle modifications (diet and exercise) have failed.

• Insulin secretagogues: Drugs that delay the absorption of carbohydrates from the gastrointestinal tract and insulin sensitizers. There are 2 subclasses of insulin secretagogues:

  • Sulphonylureas: These drugs stimulate pancreatic beta-cell insulin secretion. Examples include Glibenclamide (glyburide), Glipizide, Chlorpropamide, Tolbutamide, and Glimepiride.

  • Non-sulphonylurea insulin secretagogues: These are newer agents that also stimulate insulin secretion but are shorter acting. Examples include Repaglinide and Nateglinide.

• Alpha-glucosidase inhibitors: These drugs slow the absorption of carbohydrates, reducing postprandial elevations in plasma glucose levels. They do not significantly lower fasting plasma glucose levels but cause a modest reduction in HbA1c. Examples include Acarbose and Miglitol.

• Biguanides (Metformin or "Glucophage"): Increase insulin sensitivity in the liver and reduces hepatic glucose production. Metformin also seems to increase peripheral insulin sensitivity by enhancing glucose uptake in the muscle. It is commonly used as the first line drug.

• Thiazolidinediones: These drugs increase the sensitivity of skeletal muscle, liver and adipose tissue to insulin without directly stimulating insulin secretion from pancreatic beta cells. They also decrease hepatic glucose production by improving hepatic insulin sensitivity. Thiazolidinediones may used in combination with other oral agents in persons achieving poor glycemic control with initial single drug therapy. By improving insulin sensitivity, thiazolidinediones may exert beneficial effects on cardiovascular risk factors. Examples include Rosiglitazone and Pioglitazone.

  • In May 2007, the U.S. Food and Drug Administration informed healthcare professionals of a potential safely issue related to rosiglitazone (Avandia; GlaxoSmithKline PLC). An on-going analysis of safety data for the treatment of type 2 diabetes mellitus using Avandia showed differing rates of ischemic cardiovascular events including heart attack or heart-related adverse events, some fatal, relative to other drugs used to treat diabetes mellitus. The clinical studies reviewed to date vary with respect to their populations, treatment regimens, and length of follow-up. Based on these data, the risk of ischemic cardiovascular events due to Avandia remain unclear. Healthcare providers should continue to carefully make individualized treatment decisions for patients with diabetes mellitus.

• Dipeptidyl pepdidase 4 (DPP-4)inhibitors: Januvia is the first of this new class of drugs which act by prolonging the activity of proteins that boost the release of insulin after blood sugar rises, such as after a meal, by blocking an enzyme called DPP-4 which breaks down these proteins. This allows those insulin-boosting proteins last longer, leading to better blood sugar control. Januvia is taken once daily.