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Acta Physiol (Oxf). 2008 Jan;192(1):117-25. doi: 10.1111/j.1748-1716.2007.01789.x.

Pathophysiology and treatment of patients with type 2 diabetes exhibiting failure to oral drugs.

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Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.


It is generally accepted that a poor glycaemic control increases the risk for development of vascular complications in diabetic patients. This advocates for early introduction of insulin treatment in patients with type 2 diabetes exhibiting a secondary failure to oral treatment. This strategy is facilitated by introduction of long-acting insulin glargine and biphasic insulin aspart 70/30. The introduction of Glucagon-like peptide-1 (GLP-1) mimetics and dipeptidyl peptidase 4 (DPP-4) inhibitors in treatment of type 2 diabetes will however, to a large extent, influence therapeutic policy. Thus we suggest that DPP-4 inhibitors or long-acting GLP-1 mimetics will be used as either first-line therapy or as an early addition to metformin. The already generated results in animal and clinical studies suggest that these two classes of antidiabetic drugs may in addition to improving glycaemic control protect islet beta-cell mass and thereby postpone development of a secondary failure. When patients treated with metformin, sulfonylurea (SU), tiazolidinediones or a combination of these drugs fail, the GLP-1 mimectics may be preferred to insulin treatment. First, the risk of hypoglycaemia is less if not combined with SU. Secondly, the body weight is usually decreased while insulin treatment increases weight. Patients not responding to GLP-1 mimetics or experiencing significant side effects will be treated with insulin. Irrespective of the policy used for the drug treatment of type 2 diabetes, exercise and proper diet will remain important for optimization of metabolic control.

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