The Case for Early Drug Therapy in Preventing Diabetes

A number of pharmacotherapies, mostly designed to reduce weight, may have a great impact on treating diabetes early on, according to Harold E. Lebovitz, MD,FACE, professor of medicine, at The State University of New York.

In his presentation at the 2010 Cardiometabolic Health Congress, titled, “Should we use Pharmacotherapy in Prediabetes,” Lebovitz highlighted a number of studies focused on weight loss and relayed how they may play a role in effectively managing diabetes and perhaps pre-diabetes.

In the DM Prevention Trials: Life Style Intervention study, the focus was on prevention onset diabetes, Lebovitz said. A recent 10-year follow-up delivers insight into the effects. Among the findings were that during the first few years of the study there was a significant rate of weight loss, but following the study the weight was regained.

During the study, all age groups showed some benefit, but in the follow-up it appeared that only the participants that were over age 60 continued to have a benefit, while the youngest participants, those age 25-44, regained their weight. For those over age 60, lifestyle changes really did reduce the chance of new onset diabetes, according to the 10-year follow-up data. When metformin was stopped, however, there was a rebound of diabetes.

In the China Da Qing Diabetes prevention program, only a small group of patients had no long-term benefits. The study sought to examine whether intense life-style intervention techniques can have long-term lasting effects in preventing onset diabetes and cardiovascular events in patients with impaired glucose control. What the study did demonstrate was that it was possible for pre-diabetic patient to develop diabetes. The patients in the combined lifestyle intervention groups had a 51% lower incidence of diabetes during the active intervention period. Over the 20-year period there was 43% lower incidence for this group as well.

Because diabetes prevention therapy has been shown to make a difference, as seen in the last highlighted study, Lebovitz suggested that A1C measures may be important in predicting diabetes and preventing the loss of beta cells.

There are a number of reasons why treating pre-diabetes with drugs should be performed, Lebovitz said:

-prevent symptoms

-prevent microvascular complications

-Prevent accelerated arthrosclerosis and macrovascular disease

Lebovitz highlighted thiazolidinedione as one possible option. In the DREAM study, which used this class of drug therapy, there was a 65% reduction in developing diabetes, he noted. What isn’t known for certain, is whether or not the drug reduces beta cells. When rosiglitazone was stopped, however the patients went on to develop diabetes, which would make it seems as though the treatment did not act to increase beta cells. In the Act Now study, which also used a drug of this class, there was an 80% decrease in the development of diabetes. Side effects associated with thiazolidinediones, however, are congestive heart failure and bone fractures.

An effective treatment currently used in Asia is acarbose, though among its chief side effects is increased production of hydrogen gas. Lebovits highlighted a study that demonstrated a significant improvement in cardiovascular outcomes when this drug was administered. The treatment also reduced the risk of developing diabetes and had a positive effect on hypertension by reducing the condition by 34%. The side effect of hydrogen gas, while unpleasant, may also have an effect on inflammation.

Orlistat, he mentioned, blocks the absorption of fat and has been shown in clinical trials to reduce the risk of developing diabetes by 45%.

Although metformin, is the only drug approved for diabetes treatment, clinical trials have demonstrated that it only has a 31% reduction in reducing the development of diabetes.

Incretin-based therapy may be another option, he said. Lebovitz highlighted a study on liraglutide and the effects on body weight, which did not return significant results on weight reduction, but was, in high doses, associated with a reduction in metabolic syndrome, he said.

The questions researchers must ask is how effective is treatment in reducing progression to diabetes and will patients be compliant in long-term treatment, he said.

Besides pharmacotherapy, bariatric surgery has shown improvements in reducing the risks of diabetes as well, he said.