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Could coupling the recent explosion in large-scale biological data to novel models for pre-competitive collaboration help tackle the challenges of innovative drug development? Bethan Hughes investigates.
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.
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.
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.
The glucose-phosphorylating enzyme glucokinase acts as a glucose sensor of the insulin-producing pancreatic islet β-cells, controls the conversion of glucose to glycogen in the liver and also regulates hepatic glucose production, and is therefore a potential therapeutic target for the treatment of type 2 diabetes. Here, Matschinsky discusses the physiological roles of glucokinase and the most recent progress in the development of pharmacological glucokinase activators.
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.
