New findings in 10 year UKPDS follow up

This just came out ahead of print in NEJM. I’ll get it posted now before the news media distort it.

The findings, based on 10 year follow up of the United Kingdom Prospective Diabetes Study (UKPDS), reported in two NEJM papers, are these:

Differences in glycemic control were lost within a year of the end of the original trial. Nevertheless, microvascular benefits persisted at 10 years and, somewhat surprisingly, macrovascular benefits (reduced MI) emerged in the insulin/sulfonylurea group and persisted in the metformin group.

Differences in BP control were lost within two years of trial completion and at 10 years there was no difference in outcomes attributable to blood pressure control.

The popular media are liable to report “blood sugar control prevents heart attacks after all, BP control doesn’t.” For those who care to think beyond the sound bite here’s my take on what’s really significant:

The benefits of glycemic control are realized years later. The benefits of BP control are shorter term, realized more in real time and require ongoing treatment.

The benefits in UKPDS were associated with hemoglobin A1C levels of 7. More aggressive glycemic targets in type 2 diabetes may be associated with macrovascular harm.

This is the first evidence that glycemic control using insulin or sulfonylureas in DM 2 may produce macrovascular benefit.

If we require that drugs for DM 2 be vetted for clinical outcomes some effective drugs may be doomed. Sulfonylureas have carried boxed warnings about macrovascular risk for decades. In today’s regulatory climate they might never have been approved.

The benefits of glycemic control included a reduction in mortality and should put to rest the debate over whether the outcomes associated with glycemic control in DM 2 are “outcomes that matter.”