Endocrine Abstracts (2009) 20 D1.3

What to do next when metformin does not work in diabetes Type 2? add incretin

Baptist Gallwitz

Universitätsklinikum Tübingen, Tübingen, Germany.

Near-normoglycaemia shold be reached as safely as possible. It should be considered, that at lower HbA1c concentrations, the proportional contribution of postprandial glucose to HbA1c is greater than at higher HbA1c values.

Sulfonylureas, glinides and insulin are associated with an increased risk for hypoglycaemia and weight gain. Therefore, these agents should not be considered in first line for the combination therapy in overweight patients with Type 2 diabetes and metformin monotherapy failure. Sulfonylureas and glinides as insulin secretagogues act glucose-independently and have a disadvantage compared to the novel incretin based therapies that are safe regarding hypoglycaemia and weight development. The only advantage of the sulfonylureas may be their low cost, but this has to be outweighed against the costs for more frequent blood glucose testing and the costs caused by severe hypoglycaemic events. Insulin can be dosed in a manner to lower glycaemic parameters to any desired goal, but also has the above mentioned limitations regarding weight and hypoglycaemias.

Acarbose has lowered cardiovascular events in IGT and in Type 2 diabetic patients. Gastrointestinal side effects are a barrier to a broad use of this compound.

Glitazones are also associated with weight gain and with fluid retention. Cardiovascular safety and the incidence of bone fractures have been discussed recently in spite of the positive cardiovascular data of the PRO-Active study.

A safe antihyperglycemic treatment not leading to hypoglycaemia and weight gain may be favourable, especially in patients with HbA1c values in the range below 7.5%, where postprandial hyperglycemia contributes to a higher degree to the HbA1c reduction. Here, the incretin based therapies may become an attractive treatment option especially for overweight patients with Type 2 diabetes.

In general, however, we will need long-term intervention studies to investigate the durability of the effect of the novel drugs and their effect on vascular outcomes and hard endpoints. These studies will have to be very large and will need to have a long duration to clarify the open questions that still remain.

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