Timely Addition of Insulin to Oral Therapy for Type 2 Diabetes

The U.K. Prospective Diabetes Study (UKPDS) has shaped our view of the management of type 2 diabetes more than any other trial. It proved that glycemic control limits retinopathy (and probably other microvascular complications) as much for type 2 diabetic patients as had previously been shown for type 1 diabetic patients (1). It defined the progressive natural history of type 2 diabetes, with declining β-cell function over time and a need for progressively more active treatment to maintain glycemic control (2). In addition, it has offered important insights into the effects of several forms of treatment.

For example, newly diagnosed patients entering the UKPDS who did not need immediate insulin therapy received intensive dietary therapy, but only 15% of them were able to reach target levels of glycemic control (fasting blood glucose ≤108 mg/dl) after 3 months, and the results were even worse after a year (3). This disappointing result indicates that lifestyle intervention alone will only occasionally be successful for patients presenting with overt diabetes. The UKPDS also reassured us that insulin and sulfonylureas do not increase cardiovascular mortality, as had been feared. It showed that glyburide caused more hypoglycemia than chlorpropamide and glipizide (1) and that metformin (4) was the one drug used that did not cause weight gain compared with therapy based on lifestyle. These insights have helped us deploy these treatments more effectively.

One of the main conclusions the UKPDS investigators themselves have drawn from their findings is that combinations of treatments will routinely be needed for type 2 diabetes (5). In this issue of Diabetes Care, they report the results of a …