DOCTOR'S VIEW ARCHIVE
Diabetes Update #10 Day 4, Monday June 13 from the American Diabetes Association National Meeting
Dr. Ruchi Mathur offers perspectives of interest on topics from the American Diabetes Association's 65th Annual Scientific Sessions (held in San Diego, California June 10-14, 2005)
This is Dr. Ruchi Mathur on the fourth day of the American Diabetes Associations 65th annual meeting. This morning housed an extensive review of the GLP-1 analog we discussed earlier, known now as Byetta.
While the benefits and potential mechanisms were discussed in detail, one of the problems that was reviewed is its short duration of action. In the body GLP-1 is broken down by an enzyme called DPP-4. GLP-1 made by the body is broken down in a matter of minutes. The new prescription GLP-1 product is altered, so it lasts a few hours. However, it will still need to be injected at least twice daily in most patients.
To overcome this problem, companies are working on two areas. The first is to try to change the compound even more to make it longer acting. The second is to try to inhibit DPP-4 from breaking down GLP-1. This session discussed ways in which research in these two areas is proceeding.
Liraglutide and CJC-1131 are compounds currently being studied which are similar to exenitide (Byetta) but have longer durations of actions. In a 5 week study liraglutide was given to patients on no medication or on metformin therapy, and compared to a group who continued on their prior regimen. After adjusting the dose for about 3 weeks, patients were then continued for 5 weeks. There was a decrease in fasting blood sugar levels in the group on liraglutide and the side effect profile was similar to Byetta, with nausea in about 25%, and withdrawal from the study in about 4%. CJC-1131 actually binds the protein albumin in the blood, so it's life span is much longer. It likely will require one shot every 1-2 days. When given to 81 patients on metformin, in 12 weeks the A1c decreased from a baseline of about 7.9 by another 1.1%. Weight dropped about 5-6 pounds and the side effects were similar to Byetta.
There are a number of DPP-4 inhibitors being studied, with names such as Vildagliptin, Saxagliptin and Sitagliptin. These agents basically inhibit 90% of the action of DPP-4 and increase the life of GLP-1 in the body by about 3 times. These agents have been tested alone and in combination with metformin, and in general, they seem to reduce A1c by about 1% over 12 weeks. The weight reduction is not as noticeable as with the GLP-1 analogs. These medications were safe and tolerability in clinical trials.
So- what does this mean? Byetta is a break-though new treatment for type 2 diabetes. However, it does involve more than one injection a day. Longer acting compounds with similar effects are being developed, and will likely be on the market in a few years. Ways to inhibit the breakdown are also being studied. These DPP-4 inhibitors have the advantage of being in a pill form, not a shot. However, we may loose some of the intensity of the weight loss effect that is so very appealing. You will no doubt be hearing more on these compounds in the upcoming months. Read and hear the next installment from the conference.
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