Insulin Therapy for Type 2 Diabetes

A number of landmark randomized clinical trials established that insulin therapy reduces microvascular complications (1,2). In addition, recent follow-up data from the U.K. Prospective Diabetes Study (UKPDS) suggest that early insulin treatment also lowers macrovascular risk in type 2 diabetes (3). Whereas there is consensus on the need for insulin, controversy exists on how to initiate and intensify insulin therapy. The options for the practical implementation of insulin therapy are many. In this presentation, we will give an overview of the evidence on the various insulin regimens commonly used to treat type 2 diabetes.

Secondary analyses of the aforementioned landmark trials endeavored to establish a glycemic threshold value below which no complications would occur. The UKPDS found no evidence for such a threshold for A1C, but instead showed that better glycemic control was associated with reduced risks of complications over the whole glycemic range (“the lower the better”) (4). For the management of type 2 diabetes, this resulted in the recommendation to “maintain glycemic levels as close to the nondiabetic range as possible” (5). However, in contrast to the UKPDS, the Kumamoto study observed a threshold, with no exacerbation of microvascular complications in patients with type 2 diabetes whose A1C was <6.5%, suggesting no additional benefit in lowering A1C below this level (2). Moreover, the intensive glycemia treatment arm of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, targeting A1C <6.0%, was discontinued because of higher mortality in this group compared with the standard therapy group targeting A1C from 7.0 to 7.9% (6). Therefore, the American Diabetes Association (ADA) recommendation of an A1C target <7.0% seems the most balanced compromise at present (7).

Another important conclusion of the UKPDS was that the risk reductions in long-term complications were related to the levels of glycemic control …