The coexistence of type 2 diabetes and obesity presents a complex therapeutic challenge. Future combination tablets may include agents to address diabetes and any accompanying cardiovascular risk factors. Injectable agents that improve glycemic control and facilitate weight loss have recently become available: the soluble amylin analogue pramlintide provides an adjunct to insulin therapy in type 1 and type 2 diabetes, and the incretin mimetic exenatide can enhance prandial insulin release in type 2 diabetes. Orally active inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-IV, agonists of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ ("dual PPARs"), and the CB1 cannabinoid receptor inhibitor rimonabant are advanced in clinical development. Many novel antidiabetic and antiobesity compounds are emerging in preclinical development.