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Do Newest Diabetes Drugs Work?

Byetta, Januvia, Galvus: 'Modest' Effect Without Weight Gain
WebMD Health News
Reviewed by Louise Chang, MD

July 10, 2007 - The newest class of type 2 diabetes drugs -- Byetta, Januvia, and the still-unapproved Galvus and liraglutide -- have "modest" effects with long-term safety still unknown.

That early verdict comes from an analysis of 29 clinical studies of the "incretin" class of drugs by Tufts University researchers Renee E. Amori, MD, and colleagues.

Aside from their efficacy, perhaps the best thing about these drugs is that unlike other diabetes drugs, they don't make people gain weight. In fact, patients taking Byetta actually lose weight (the drug is under investigation as a weight loss agent).

"Incretin therapy offers an alternative option to currently available [blood sugar-reducing] agents for nonpregnant adults with type 2 diabetes with modest efficacy and a favorable weight change profile," Amori and colleagues conclude.

In terms of diabetes control, perhaps the best thing about incretin drugs is that the drugs affect chemical signals sent out by the gut when it encounters food. This means that the major effect of incretins is to control glucose levels immediately after a meal -- a major problem for people with type 2 diabetes.

The downside: While the drugs seem safe in short-term studies, their long-term safety remains unknown. Nearly all the studies analyzed by Amori and colleagues lasted less than eight months.

2 Incretin Families: GLP-1 Analogs and DPP4 Inhibitors

Currently, there are two incretin families. Byetta and liraglutide are glucagon-like peptide 1 (GLP-1) analogs. This means they mimic the insulin-boosting effects of natural GLP-1, which tend to diminish the longer a person has diabetes.

The problem with GLP-1 analogs is that they must be given by injection. This led to the development of a second class of incretins: the dipeptidyl peptidase 4 (DPP4) inhibitors. DPP4 is an enzyme that quickly degrades natural GLP-1. Januvia and Galvus inhibit DPP4, thus increasing natural GLP-1.

This could possibly present long-term problems, as some important immune cells need DPP4 to fight infections. Indeed, increased urinary tract infections seem to be a side effect of the DPP4 inhibitors. Amori and colleagues warn that until more is known about their safety, these drugs should not be used by people who get frequent urinary tract infections.

Amori and colleagues urge continued study of both the effectiveness and the safety of incretin drugs in order "to determine their role among the many available and well-established therapies for type 2 diabetes."

The researchers report their study in the July 11 issue of The Journal of the American Medical Association.

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