The rapid growth in the prevalence of type 2 diabetes is increasing the need for effective therapeutic interventions. However, although multiple classes of diabetes drugs are available, achieving long-term control of blood sugar is often a major challenge, in part owing to treatment-limiting adverse effects. With these challenges in mind, this special collection of articles from Nature Reviews Drug Discovery focuses on emerging therapeutic approaches and targets for type 2 diabetes.
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Perspectives
Therapeutic targets to reduce cardiovascular disease in type 2 diabetes
Cyrus DeSouza & Vivian Fonseca
doi:10.1038/nrd2872
Nature Reviews Drug Discovery 8, 361-367 (2009)
Cardiovascular disease associated with type 2 diabetes has become a major issue in the development of new diabetes therapies. DeSouza and Fonseca review the background to and implications of recent regulatory guidance for cardiovascular risk assessment of new antidiabetic agents, and discuss the potential beneficial cardiovascular effects of selected agents currently in development.
Reviews
Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes
Bo Ahrén
doi:10.1038/nrd2782
Nature Reviews Drug Discovery 8, 369-385 (2009)
Therapies based on the incretin hormone glucagon-like peptide 1 (GLP1) have proved to be successful in the treatment of type 2 diabetes. In this article, Ahrén reviews recent progress in the development of improved GLP1 modulators and discusses the therapeutic potential of other islet β-cell G protein-coupled receptors that are involved in the regulation of islet function, including GPR40 and GPR119.
SGLT2 inhibition — a novel strategy for diabetes treatment
Edward C. Chao & Robert R. Henry
doi:10.1038/nrd3180
Nature Reviews Drug Discovery Advance online publication (2010)
Preventing the reabsorption of glucose in the kidney by inhibiting the sodium–glucose co-transporters (SGLTs) is emerging as a promising new strategy to treat type 2 diabetes. Here, Chao and Henry give an overview of the role of the kidney in glucose homeostasis and discuss the development and potential of SGLT2-selective inhibitors, reviewing those agents currently undergoing clinical investigation.
Targeting the CNS to treat type 2 diabetes
Darleen A. Sandoval, Silvana Obici & Randy J. Seeley
doi:10.1038/nrd2874
Nature Reviews Drug Discovery 8, 386-398 (2009)
The growing appreciation of the regulatory role of the central nervous system (CNS) in energy and glucose homeostasis has the potential to lead to more effective long–term treatments for obesity and type 2 diabetes. Here, Sandoval and colleagues discuss the CNS pathways involved, identify promising therapeutic targets and strategies for diabetes and consider the associated challenges hampering the development of new agents.
Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials
Nigel A. Calcutt, Mark E. Cooper, Tim S. Kern & Ann Marie Schmidt
doi:10.1038/nrd2476
Nature Reviews Drug Discovery 8, 417-430 (2009)
Long-term diabetes increases the likelihood of developing complications such as macrovascular disease, nephropathy, retinopathy and neuropathy. This Review highlights the range of pathologies that are precipitated by hyperglycaemia and discusses recent developments in preclinical and clinical research for each of these complications.
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