Antidiabetic medications in the pipeline.

There is an extensive pipeline of therapies for diabetes mellitus. It has been known for the past three decades that obesity is a key pathophysiological player, involving inflammation, insulin resistance and metabolic dysfunction leading to type 2 diabetes and to significant cardiovascular, renal and hepatic complications, all central to the metabolic syndrome. On the basis of this knowledge and the disposition of drugs with multiple effects on different disease components, the diabetes therapeutic paradigm has shifted from merely glucocentric to multitargeted against these interconnected pathways.Much more recently, incretin-based multi-agonists have been developed that deliver unprecedented glycemic and weight benefits as well as weekly insulins and oral GLP-1 agonists that are able to reduce the burden of injectable therapies. An antibody-peptide conjugate that acts as a dual GLP-1/GIP receptor modulator has also shown promising results. Today, novel insulin sensitizers are modulating metabolic pathways towards higher energy expenditure with fewer side effects. Adjunctive agents for type 1 diabetes are improving glucose control while reducing hypoglycemia risk. Finally, drugs designed to restrain the inevitable muscle mass loss caused by antiobesity treatments are being tested. The diabetes pipeline is rich and there is hope that in the next few years, the therapeutic landscape will be further transformed with even more efficacious and individualized treatments.