Insulin resistance and the defect of insulin secretion are two basic pathogenetic mechanisms in the development of type 2 diabetes mellitus. So far, the therapeutic modalities focused on influencing of these mechanisms. Sulfonylureas stimulate insulin secretion regardless of food intake. Under physiological conditions the food intake stimulates incretin secretion from the small intestine. Incretins are able to stimulate insulin secretion from the pancreatic β-cells. This effect is most pronounced in glucagon-like peptid 1 (GLP-1). Because GLP-1 has a very short half-life in the circulation as a result of degradation by dipeptidylpeptidase IV (DPP-IV) two groups of drugs have been recently developed, which lead to enhancement of incretin effect. GLP-1 analogs (exenatide and liraglutide) are not degraded by DPP-IV, therefore subcutaneous application is possible. Beside the stimulation of insulin secretion these drugs suppress glucagon secretion, delay gastric emptying and reduce food intake. In addition to increased glycemic control (HbA1c reduction of approximately 1 %) GLP-1 analogs lead to reduction of body weight. DPP-IV inhibitors (sitagliptin and vildagliptin) could be given orally. Their effect on glycemic control is similar to GLP-1 analogs, but no body weight reduction was observed. Enhancement of incretin effect is a new, hopeful way of treating type 2 diabetes mellitus.