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 β-cells is largely responsible for the deterioration in glycaemic control. Preservation of β-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 β-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 β-cell function is at its highest, allowing maximal benefit to be obtained from the insulin secretion-promoting abilities of the sulfonylureas and the β-cell-protective effects of the thiazolidinediones.