Purpose and overall aim
This project aims to develop incretin therapy as a glucose-reducing strategy in type 2 diabetes (T2D). Its particular focus is to understand the mechanisms of incretin therapy and to optimize its clinical positioning. This mission is achieved by an interdisciplinary approach with complementary studies in subjects with T2D, healthy volunteers and experimental animals.

Background to the project
Type 2 diabetes has an increasing global occurrence with a high burden both for the individual and for the society. Morbidity and mortality are significant in diabetes and the disease results in a high demand for health care. Management of the disease involves a proper health care system in association with life style changes and pharmacotherapy. The overall goal of therapy is to prevent secondary complications by achieving normal metabolism without adverse events.
Reducing hyperglycemia is an important part of therapy. This usually requires glucose reducing pharmacotherapy. The first line pharmacotherapy is metformin. When this is insufficient alone, six options are today common for double therapy, and these may be followed by triple therapy in various combinations (1). Although all these options lower glucose, some are associated with hypoglycemia and weight gain. For optimization, differentiation and positioning of the therapies and for understanding their mechanisms, advance in knowledge is required.
Incretin therapy is today an establish glucose-reducing option, both in double therapy with metformin, in triple therapy in several combinations and in monotherapy in subjects when metformin is not possible. It consists of DPP-4 inhibitors and GLP-1 receptor agonists (2). Incretin therapy targets the pathophysiology of T2D, mainly the islet dysfunction (3), it has only a low risk for hypoglycemia and does not result in weight gain. It is also safe, as evident fromd large cardiovascular outcomes trials on DPP-4 inhibitors and GLP-1 receptor agonists.
This long-term project has for decades held a core position in the development of incretin therapy. We thus presented the first studies showing that GLP-1 improves glycemia in T2D (in 1992; 4) and we also presented the first study showing that DPP-4 inhibition is glucose reducing in T2D (in 2002; 5). The project has, furthermore, throughout the years explored the clinical use of incretin therapy and examined mechanisms of its actions (3).
Within a few years, the landscape will change considerably, since many incretin drugs will become generic. The price of the incretin drugs will then reduce and the use of incretin therapy will increase. To prepare for this changing landscape it has become even more important than before to further advance the clinical and scientific knowledge of the therapy.