It's a curious case of missing evidence. When a diabetes specialist searched the medical literature looking for proof to support the use of glucose-lowering drugs for Type 2 diabetes, he couldn't find it.

That absence of evidence raises questions about one of the most firmly entrenched beliefs in modern medicine — that tightly controlling elevated blood sugar will reduce the risk of death, stroke, kidney failure, blindness and other dire outcomes associated with Type 2 diabetes.

"Does controlling your sugars reduce the risk of complications?" Dr. Victor Montori, of the Mayo Clinic in Rochester, Minn., asked in a paper released this month in the journal Circulation: Cardiovascular Quality and Outcomes. "Most experts say yes. The evidence appears to say 'not so fast.'"

Conventional wisdom challenged

Right now, millions of people are taking glucose-lowering drugs, routinely pricking their finger to check their blood sugar level, and fretting over test results that aren't as low as their doctor wants them to be in hopes of avoiding the dire outcomes associated with the disease.

But with the drugs comes the risk of side-effects including weight gain and, if blood sugar falls too low, dizziness, coma or even death.

'Our thinking about it may have been flawed.' - Dr. Victor Montori, Mayo Clinic, Rochester, Minnesota

Add to that the distress of being branded with a "disease" based on a routine blood test, even though most of the people diagnosed with Type 2 diabetes have no symptoms.

"We have taken for granted or assumed that the evidence was very clear that if you control you blood sugars tightly, you will prevent diabetes complications," Montori said. "The answer is less clear than expected and, as a result, it would suggest that our thinking about it may have been flawed."

His conclusions challenge the conventional wisdom of many medical specialists, and contradict most clinical practice guidelines.

"Over 90 per cent of experts were saying that controlling blood sugars tightly was associated with a reduction in your risk of going blind or of needing dialysis or having to undergo an amputation," Montori said. "But when we looked at the evidence for that, we could not see any signal that would suggest that is true despite the question being asked at least since the 1970s."

Dr. Victor Montori

Dr. Victor Montori, of the Mayo Clinic, is calling for a review of the standard approach to treating Type 2 diabetes. (Mayo Clinic, Rochester Minn.)

The finding reveals a divergence in professional opinion based on the same set of facts, and it exposes a dilemma in the science of Type 2 diabetes — that doctors don't completely understand the relationship between blood sugar and the disease.

"There is lots of debate and discussion as to what exactly is the causal relationship," said Dr. Hertzel Gerstein, diabetes researcher at McMaster University in Hamilton.

It's possible that some other mechanism, or a combination of factors besides high blood sugar is responsible for potential long-term complications.

'We have to make recommendations based on incomplete evidence.' - Dr. Hertzel Gerstein, McMaster University 

"We know, for instance, that the higher the blood sugar the higher the risk of heart attacks, the higher the risk of cancer, the higher the risk of strokes," Gerstein said. "But whether other things related to the diabetes are causing those things is not known."

Gerstein said doctors are forced to "make recommendations based on incomplete evidence and some of the trials have not answered all of the questions."

Call for better evidence

But the uncertainty is serious enough to require a change in the way Type 2 diabetes drugs are approved, according to a research group at the University of British Columbia.

The UBC Therapeutics Initiative has called on Health Canada to demand better evidence that glucose-lowering drugs improve long-term outcomes before the drugs are approved.

"All we truly know is that the drugs reduce blood glucose in the short term. That's the basis of the evidence. So clinicians and patients are taking a bit of a leap in faith that this will translate into reductions in Type 2 diabetes-related complications," said Cait O'Sullivan, a member of the Therapeutics Initiative research team.

There is a risk that all of the attention on blood sugar levels is distracting researchers from pursuing new leads. If doctors check the shelf for other medications that do something beyond glucose control, they will find that medical cupboard is bare, Montori said. 

"We have over nine different drug classes that can control blood sugars," he said. But, he added, there is no such list of therapies that try to treat Type 2 diabetes in a different way. "That suggests to me that we have a blind spot, and I think that may have come from the fact that all of our experts have concluded — I think prematurely — that the answer is in."