Insulin and lipid metabolism: new developments in drug therapy

Abstract

Current treatments for non-insulin-dependent diabetes mellitus (NIDDM) remain far from ideal. The presence of both hyperinsulinaemia and resistance to insulin action in NIDDM challenges the rationale of treatments which primarily boost insulin secretion. Novel therapeutic strategies focus mainly on increasing peripheral sensitivity to endogenous insulin, an approach which has the potential not only to treat, but also to prevent NIDDM in high-risk individuals. The most promising new agents are the thiazolidinedione derivatives, in particular troglitazone. Thiazolidinediones are ligands for a specific subtype of the peroxisome proliferator activated receptor (PPAR), and decrease plasma glucose levels in both obesity and NIDDM, while at the same time reducing circulating insulin and free fatty acid levels. The current development status of these agents is reviewed, along with an assessment of their potential in the prevention and treatment of diverse pathophysiological states characterised by insulin resistance, including atherosclerosis and polycystic ovarian disease. Reference is made to the current status of other experimental agents including hydantoin derivatives, (3)-adrenoceptor agonists, and inhibitors of lipolysis.