Earlier use of drugs, stricter use of bariatric surgery recommended
The American Association of Clinical Endocrinologists held its annual meeting this year in Houston. The five-day conference covered a broad range of subjects in endocrinology, but there was a definite focus on diabetes. One topic that had a larger role this year than in previous years was prediabetes and early treatment/prevention of diabetes. Even in presentations that did not deal specifically with prediabetes, audience members (most of whom were clinical endocrinologists) often asked speakers questions on the off-label use of diabetes drugs for patients with prediabetes. Right now, there are no drugs specifically indicated for prediabetes, but there were several talks this year on the early use of diabetes and cardiovascular drugs earlier in the disease process than what has been seen before.
One class that looks particularly promising for prediabetes is the incretin class. Currently, the only commercially available incretin today is Byetta (generic name: exenatide), which is injected twice daily. Incretins seem ideal for treating prediabetes, since they promote insulin secretion by the pancreas (but rarely cause hypoglycemia), lead to weight loss, and lower A1c. In addition, Dr. Harold E Lebovitz, MD (SUNY Brooklyn, Health Sciences Center, New York, NY) reviewed the evidence that GLP-1 has cardioprotective effects. Although only preliminary data is currently available, incretins appear to improve heart function and circulation as well as cholesterol levels. There is even some data from a clinical trial called ACCORD that suggest that patients taking Byetta had a lower incidence of mortality. Unfortunately, the trial was not designed specifically to look for this effect, so no definitive conclusions can be drawn. Ken Fujioka, MD (Scripps Clinic – Del Mar, San Diego, CA) even discussed the possibility of incretins as a weight loss treatment. Although this class does not lead to weight loss that is as significant as some other medications, it has the unique advantage that there is no rebound effect; many weight-loss medications show a great deal of weight loss in the first months of use, but weight is gradually gained back over time. The major drawbacks for incretins are nausea (which can occur in up to one-third of people who take exenatide, though if patients ask their doctors to help with careful titration, fewer patients suffer) and the fact that exenatide must be taken by incretin pen (like an insulin pen) twice daily (in some respects we think some doctors, particularly primary care doctors whose time is very limited, are more bothered by this than patients).
A presentation by Dr. Alan Garber (Baylor College of Medicine, Houston, TX) focused on the early use of insulin-sensitizing TZDs (a class which includes Avandia and Actos) to reduce the incidence of diabetes. The DREAM trial showed a 62% reduction in the incidence of diabetes in people who took Avandia and the blood pressure lowering drug ramipril. Similar results have been seen with Actos. Unfortunately, TZDs are associated with a roughly two-fold increase in risk for heart failure and lead to weight gain; so many patients would not be well suited to TZDs as a preventive therapy. Dr. Garber concluded his talk on a controversial note, asserting that lifestyle intervention may be overemphasized in the early treatment of diabetes, and that medication may be a more effective first-line therapy for many people. The opposite opinion is more often expressed; physicians worry that relying more on medication will suggest that the problem has been addressed, and that patients will decide there is little or no need to make an effort with lifestyle changes. We would love to see insurance companies create lifestyle incentives for patients and reward positive results, but we unfortunately don't see this happening anytime soon.
In addition to preventing the progression of the metabolic symptoms of diabetes, early medical intervention to reduce cardiovascular risk factors was a hot topic. People with diabetes have highly increased risks of coronary heart disease, heart failure, and stroke. Thus, people with diabetes are ideal candidates for medications that target cardiovascular disease, such as statins (Lipitor, Crestor, Zocor, and others), fibrates (Tricor, Lopid, Bezalip, Modalim and others) and niacin. Statins, in particular, have been shown to lower major vascular events (such as heart attacks) by 21% in people with diabetes. However, one speaker suggested that without a specific FDA indication for prediabetes, beneficial drugs like statins or incretins might not be prescribed as often as they should be.
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