Preventing Type 2 Diabetes
Can drugs prevent the onset of type 2 diabetes? One class of drugs shows promise, but it has its drawbacks.
A New Direction?
Based in part on the results of the TRIPOD study, Buchanan
believes the emphasis of diabetes treatment needs to be shifted.
"Basically, right now, we treat people whose glucose levels
are already high enough to cause long-term complications and we try to get
their levels lowered," he says. "But by the time someone has gotten to
the point of diabetes, they've probably lost about 80% of their beta-cell
function. Someone with just Impaired glucose tolerance [an aspect of
pre-diabetes] has already lost about 50% of their beta-cell function."
Buchanan wants diabetics and doctors to understand better the
difference between the manifestations of disease -- heightened glucose levels
-- and the loss of beta-cell function that may be causing them.
"The current paradigm of diabetes treatment is focused on
the sprint -- what your glucose levels are -- instead of the marathon, which is
how the disease is progressing," he says.
However, other experts caution that the results of the TRIPOD
study and the effectiveness and safety of TZDs need to be confirmed.
"TZDs are an incredibly important addition to our set of
tools," says Fran Kaufman, president of the American Diabetes Association
and division head of endocrinology at the Children's Hospital Los Angeles. But
she cautions that more studies need to be done. "Whether other studies will
show a similarly robust effect of TZDs [as the TRIPOD study did] is something
we just don't know."
The Risks and The Costs
There are potential dangers to TZDs. This was most evident in
2000, when the Food and Drug Administration asked the manufacturer of Rezulin
to withdraw it after reports of severe and sometimes fatal liver poisoning. The
two other TZDs that are currently available, Actos and Avandia, have not shown
the same risks and other TZDs are currently in various stages of development.
However, the FDA still recommends that liver function of people using TZDs be
The problems with Rezulin illustrate the risks of using any
newly developed drug. "Like any drug that's only been used for a short
time, we just don't know what the long-term risks might be of TZDs,"
As noted, TZDs have also been connected with weight gain. While
the extra fat may be subcutaneous, and thus not as dangerous as visceral fat,
the long-term effects of the weight increase aren't known; some patients gain
so much weight that treatment needs to be stopped. Studies have also shown an
increase in the risk of edema -- the build-up of fluid in tissue -- from TZD
There have been reports of other potential problems, and one
survey of patients using TZDs found that the risk of congestive heart failure
actually increased, in contrast to studies demonstrating the cardio-protective
characteristics of the drugs.
Finally, the financial costs of TZDs may hamper their
usefulness; they are significantly more expensive than other drugs used to
treat diabetes. While Kaufman hopes that prices will drop as more TZDs are
released, Buchanan is concerned that this may not happen until the patents on
particular TZDs expire.