What’s going on with diabetes

VADT is yet another negative trial showing a lack of benefit from controlling blood sugars.

That makes three negative trials in the last 12 months.

  • ADVANCE trial: 11,140 people randomized to gliclazide in order to lower the A1c to 6.5, the control group achieved 7.3%. This lowered combined micro- and macrovascular complications by 10% 18.1% vs 20% after a median of 5 yrs (p=0.01). However the difference was entirely driven by a 21% reduction in nephropathy, with no reduction in retinopathy, macrovascular complications or reduction in CV death or death from any cause.
  • ACCORD Trial: 10,251 people randomized to usual care (A1c 7.0-7.9) or intensive care (A1c under 6%). There was no difference in the primary composite outcome of non-fatal heart attack and strokes and CV mortality. Unfortunately there was a significant increase in total mortality (p=0.04) with high mortality in the intensive therapy group.

All three of these trials were looking to prove that better glycemic control could reduce strokes and heart attacks. We have known since the early nineties that good glycemic control prevents or delays microvascualr complications (kidney disease, blindness, neuropathy) but the data on cardiovascular disease was lacking. This is important because relatively few diabetics develop ESRD and most patients die of heart disease, a macrovascular complication. For example in type 1 diabetics the 20 year risk of developing ESRD is only 2.2%, while the risk of death is four times that at around 10%.

Unfortunately, this looks like a bust. Not one of the trials have shown any sign that improved glycemic control translates into reduced heart attacks or strokes.

Here is a powerpoint lecture on DM I gave a year ago. SlideShare kind of butchers the formatting so if you are really interested download it rather than whatch in the online viewer.