The pathophysiology of hyperglycemia in type 2 diabetes (T2DM) involves 3 main defects: insulin deficiency, excess hepatic glucose output, and insulin resistance. Oral anti-diabetic agents act in a variety of ways. These include agents that stimulate insulin secretion, reduce hepatic glucose production, delay digestion and absorption of intestinal carbohydrate or improve insulin action. Because of improved knowledge of pathophysiology, new drugs with mechanisms of action focussed on specific pathophysiological alterations have appeared, in order to utilize all the possibilities of treating this condition. Here, we focus on the new agents used in the latest years and the overcoming ones in future, in particular incretin-based therapies, drugs inhibiting kidney glucose reabsorption (SGLT2 inhibitors), and glucokinase activators. The strategy for new drug development advocated here is to establish a broad range of anti-diabetic medicines with different mechanisms of action and potential opportunities for effective combination therapies.
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