Endocrine Abstracts

The UKPDS trial confirmed that improving glycaemic control (median 0.9 % HbA_1c difference over median 10 years), with sulphonylurea or insulin therapy, could reduce significantly the risk of microvascular complications (25%, p=0.0099) and was associated with a 16% trend (p=0.052) to a reduced risk of coronary heart disease (CHD). In overweight UKPDS patients allocated metformin as first line therapy the 0.6% median HbA_1c difference obtained was associated with a similar trend to risk reduction in microvascular complications (29%, p=0.19) but also showed a 39% statistically significant risk reduction (p=0.010) for CHD. This unexpectedly large risk reduction suggests that metformin may have a specific cardiovascular protective effect. Additional UKPDS statistical analyses have shown that the degree of cardiovascular risk reduction obtained with metformin is not due to concomitant changes in other variables measured, including body weight, plasma triglycerides and plasma insulin. The suggestion that metformin may act like aminoguanidine is also probably incorrect given that no enhanced risk reduction was seen for microvascular complications. It is possible, however, that the circa 25% drop in mean plasma insulin levels associated with metformin therapy could induce other potentially beneficial changes, such as a reduction in plasminogen activator inhibitor 1 levels. To examine a possible dissociation between metformin's glucose lowering and cardioprotective roles the relationship of metformin doses to CHD risk reduction was investigated. No differences were seen in the degree of CHD risk reduction when either the metformin dose was assessed as the average dose over time, or the dose being taken at time of the CHD event. From this evidence base it would seem appropriate that those with type 2 diabetes who can only tolerate low doses of metformin should continue to take it concomitant with other agents to optimise glycaemic control.