Pioglitazone and sulfonylureas: effectively treating type 2 diabetes

Type 2 diabetes is characterised by a gradual decline in glycaemic control and progression from oral glucose-lowering monotherapy to combination therapy and exogenous insulin therapy. Functional decline of the insulin-secreting beta-cells is largely responsible for the deterioration in glycaemic control. Preservation of beta-cell functionality, in addition to maintaining glycaemic control and reducing insulin resistance, is now regarded as a key target for long-term management strategies. Early, aggressive intervention with combination therapy is emerging as a valid approach to optimise long-term outcomes and combining agents with differing modes of action and secondary effect profiles should prove valuable. Sulfonylureas and thiazolidinediones exert their glucose-lowering effect through differing mechanisms of action - the sulfonylureas by stimulating insulin secretion, whereas the thiazolidinediones are insulin sensitisers. Both agents offer excellent improvements in glycaemic control when given as monotherapy or in combination. The thiazolidinediones protect beta-cell structural and functional integrity and functionality and complement the sulfonylureas by inducing and maintaining improvements in insulin resistance, the abnormal lipid profile associated with type 2 diabetes and other cardiovascular risk factors. Thus, there is a strong rationale to support the addition of thiazolidinediones to sulfonylureas as a treatment option for type 2 diabetes. This combination may be particularly effective in the early stages of the disease when beta-cell function is at its highest, allowing maximal benefit to be obtained from the insulin secretion-promoting abilities of the sulfonylureas and the beta-cell-protective effects of the thiazolidinediones.