UNC’s John B. Buse on Developments in Diabetes
Scientist Interview: November 2011
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Are there new drugs coming down the pipeline that will have a significant impact on therapy?
From the drug-development viewpoint, the other very exciting class of therapy, which is under review by the FDA, involves so-called SGLT2 inhibitors. They work in the kidney, where normally all sugar in your blood is filtered into the urine space and then the body reclaims the stuff that it wants, like glucose. SGLT2 inhibitors block one of the glucose transporters in the kidney and cause people to basically pee out sugar. These are fairly powerful blood sugar-lowering agents, and they’re also associated with weight loss and some improvement in blood pressure. Their approval would create a treatment pathway where metformin, GLP-1 receptor agonists, and SGLT-2 inhibitors would be three tools that lower glucose and weight and do not cause hypoglycemia.
As the incidence of diabetes in this country steadily increases, what do you think could work to curb this epidemic?
Well, one hope is that by doing community-based screening for people with risk factors for developing diabetes, we can do lifestyle interventions and/or consider early drug therapy with something like metformin that will help slow or stop the progression of the disease. We should be able to do that. It just turns out that it’s extremely expensive to treat everybody who’s at high risk for developing diabetes. It would also be fairly expensive to do glucose tolerance testing, for instance, in everybody who seems to be at high risk of developing diabetes, to decide who’s going to be treated and who’s not. There is as yet no agreed-upon protocol that Medicare or insurance companies should pay for identifying people in a pre-diabetic state and intervening. That’s probably a mistake. We can likely do better if we catch patients earlier, and the real question is, how early do we really want to catch people?
If the consequences of diabetes are dependent on elevations in blood sugar, the earlier we catch them—at lower blood-sugar levels—the more downstream problems we’ll prevent. If we catch them when their blood sugar is 126, for example, which is what the current guidelines suggest, we may prevent 90% of downstream problems. If we catch them at 100 or 110, maybe we’ll prevent 97% of the problem. If we prevent the rise of blood sugar at 90, maybe we prevent 99% of the problem. But whenever you lower that cut point, you’re adding not hundreds of thousands of people, but literally tens of millions of people to treatment programs. But the argument has been that the real expense in diabetes is the complications and the expensive therapies that people need as a consequence. So it’s unclear what that cut point should be.
"We have so many tools now, but there’s a lack of clarity about what are really the best ways to treat diabetes," says John B. Buse of the University of North Carolina School of Medicine, Chapel Hill. "
Is there any particular research out there at the moment that really excites you about its potential for diabetes treatment?
It may not be totally relevant to type 2 diabetes, but it’s certainly applicable and certainly exciting: I’m referring to developments in the glucose sensor business. We’re now able to measure blood sugar in real time and, at least theoretically, hook the glucose sensor up to a pump that delivers a drug to normalize blood sugar and basically fix the hyperglycemia problem. This is most applicable in type 1 diabetes, where the problem is that the body doesn’t make insulin. If the pump delivers insulin when the sensor detects high blood sugar and not when it’s normal, it would basically solve the problem of type 1 diabetes. It would be applicable to type 2 diabetes, but it’s likely to be so expensive that we’d still favor alternative approaches. Although with those types of sensors, we might think about delivering drugs other than insulin—some alternative therapy, for instance, like these GLP-1 agonists.
Another area I think is pretty exciting is adult stem cells—the idea that we could create an unlimited supply of insulin-producing cells from a patient to put back into the same patient, solving their diabetes problem. That could be very successful in managing type 2 diabetes.
Where do you think researchers should focus their attention at the moment? What are the major needs in the field right now?
We have so many tools now, but there’s a lack of clarity about what are really the best ways to treat diabetes. One hope might be that, with the advent of wide distribution of electronic medical records, we can find cheaper ways of doing large-scale human studies and following populations to see how interventions are used and how well they work. So I agree with people who have advocated for so-called comparative effectiveness research.
We also need health-service research on how to deliver care in a way that patients find acceptable and are willing to work into their lives. The aim is to improve adherence and assure that people take their drugs and engage in the behaviors that are important for optimal outcomes. I think all that is very important. One area in which the University of North Carolina is taking the lead is the idea that doctors and nurses may not be the best way of delivering education and support to patients dealing with a chronic illness like diabetes. Doctors and nurses are expensive and not always available. We only see patients for 15 minutes two to six times a year, which isn’t enough. Maybe using peer supporters—other people with diabetes who are active in the community and successful in their lives and in the management of the disease—might be much more effective in helping patients find a way to better control their diabetes.
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