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DPP IV Inhibitor Closer To Reality

Sep 21, 2004

The reduction in HbA1c of 1.1% was maintained to one year, with no reported weight gain. Clinical results presented at the European Association for the Study of Diabetes (EASD) meeting in Munich last week suggest that LAF-237 given in combination with metformin, one of the most widely prescribed oral antidiabetic agents worldwide, improves control of glucose as measured by hemoglobin A1C (HbA1c) levels.

This is crucial, because while most oral antidiabetic agents are initially effective at achieving acceptable glycemic control in patients with type 2 diabetes, it is well-known that HbA1c levels increase as the disease progresses and good glycemic control is seldom maintained in the long-term, even with combination therapy. And poor glucose control is intrinsically linked to the development of the damaging consequences of diabetes, such as nerve, eye and heart disease.

LAF-237 is an inhibitor of dipeptidyl peptidase (DPP)-IV, an enzyme involved in the breakdown of two hormones, glucagons-like peptide (GLP-1) and gastric polypeptide (GIP), that are involved in boosting insulin activity after a meal .

The 12-month, Phase II study compared the addition of placebo versus once daily LAF-237 to patients’ regular dose of metformin. The results showed that the increase in HbA1c each month was less in patients treated with LAF-237 than those on placebo and that by 12 months the overall difference in HbA1c was 1.1 per cent.

An HbA1c reduction of 1.1 per cent seems small, but is impressive for an oral antidiabetic agent, particularly as it was achieved on top of existing treatment with metformin. Moreover, the reduction in HbA1c was maintained to one year, whereas often early treatment benefits diminish over time with oral antidiabetic drugs.

There was also no reported weight gain with LAF-237, a side effect observed with almost all existing oral therapies and one of the biggest challenges faced by diabetologists. This increase in weight is thought to contribute to the already elevated risk for diabetics of going onto develop heart disease.

According to the EASD, the DPP IV inhibitors are among the more promising new therapies in the pipeline for the treatment of type 2 diabetes, which currently affects 37 million people in the top seven markets and is expected to grow to 50 million people by 2012.


Studies have suggested that mental function is worse in people with diabetes, and new research published in a recent issue of Neurology shows that risk for dementia is twice as high in older women with diabetes and pre-diabetes as it is in older women with normal blood sugar levels.