New pharmacological approaches to glycemic control

The search for improved antidiabetic drug therapies must take account of th e multiplicity of endocrine and metabolic disturbances and the attendant ri sks and complications of diabetic states. Accordingly, a diversity of new p harmacological approaches is required. Potential agents to improve and part ially mimic insulin action include agonists of the peroxisome proliferator- activated receptor-gamma, vanadium compounds, and possibly in special circu mstances, IGF-1. Treatments aimed primarily at diabetic dyslipidemia and ob esity should also combat insulin resistance. Short-acting nonsulfonylurea i nsulin secretagogues will facilitate the release of extra insulin to coinci de with meals. Glucagon-like peptide 1 analogs also offer a means to augmen t nutrient-stimulated insulin release. Postprandial hyperglycemia might be further targeted with new cr-glucosidase inhibitors and agents that delay g astric emptying. With a deeper appreciation of the fundamental lesions of i nsulin resistance, defective beta-cell function, and abnormal glucose metab olism, novel interventions against these targets are envisaged.