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Diabetes Treatment (cont.)

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DPP-IV inhibitors

GLP-1 in the body is broken down by an enzyme called DPP IV. Logically, you can either make a synthetic GLP-1 that is not broken down by this enzyme (for example, Byetta) OR you could try to stop the enzyme that breaks down the GLP-1 your body already makes. Hence, the new class of drugs called DPP IV inhibitors. They do just that, that is, they inhibit this enzyme from breaking down GLP-1. This allows GLP-1 already in the blood to circulate longer. There are a number of companies working on this class of drug.

A few years ago, the FDA approved the first drug in this class made by Merck and called sitagliptin (Januvia). Januvia can be used in combination with certain other medications and must be dose adjusted in patients with poor kidney function. In August 2009, a second drug in this class was approved made by Bristol Myers Squibb and Astra Zeneca called saxagliptin and marketed as Onglyza. In 2011, another drug in this class, linagliptin, marketed as Tradjenta was approved.

These drugs have essentially the same side effect profile as Byetta; however, they are in pill form. While Byetta has a significant weight loss profile, DPP-IV inhibitors so far have had no effect on weight.

Combination medications

Glyburide/metformin (Glucovance), rosiglitazone/metformin (Avandamet), glipizide/metformin (Metaglip), and pioglitazone/metformin (Actoplus met), and metformin/sitagliptin (Janumet) are are five relatively new combination pills that are on the market to treat diabetes.

  • Glucovance combines glyburide with metformin in varying doses.
  • Avandamet is a combination of varying doses of Avandia and metformin.
  • Actoplusmet is a combination of varying doses of pioglitazone and metformin.
  • Metaglip is a combination pill containing glipizide and metformin in varying strengths.
  • Janumet is a combination of two drugs, metformin and sitagliptin.

The benefit to these combination drugs is that there are fewer pills to take, hopefully leading to better compliance. While they work well, I personally like to give patients individual medications until I know what doses are working, and then switch to a combination pill once the patient has been stable on the doses of individual medications for a period of time.


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