Battling Blubber

August 22, 2005

The obesity epidemic just will not go away. Neither will the long list of health conditions associated with obesity. The link between abdominal obesity and some of these conditions is so clear that it has been included in the diagnosis of metabolic syndrome. Metabolic syndrome isn't exactly a disease; it's a set of risk factors that researchers and clinicians have identified. The list of risk factors includes abdominal obesity, elevated triglycerides, low HDL cholesterol, and elevated blood glucose levels. People with metabolic syndrome are at greater risk of developing diabetes, heart disease, and stroke. Furthermore, people with metabolic syndrome may get sicker and suffer more than people without it.

The obesity epidemic just will not go away. Neither will the long list of health conditions associated with obesity. The link between abdominal obesity and some of these conditions is so clear that it has been included in the diagnosis of metabolic syndrome. Metabolic syndrome isn't exactly a disease; it's a set of risk factors that researchers and clinicians have identified. The list of risk factors includes abdominal obesity, elevated triglycerides, low HDL cholesterol, and elevated blood glucose levels. People with metabolic syndrome are at greater risk of developing diabetes, heart disease, and stroke. Furthermore, people with metabolic syndrome may get sicker and suffer more than people without it.

"The concept of metabolic syndrome has been out there for a long time," said Holly Wyatt, M.D., assistant professor of medicine in the division of endocrinology, metabolism, and diabetes at the University of Colorado Health Sciences Center. However, the specifics on how to diagnose it are new.

There are slightly different guidelines for diagnosing metabolic syndrome, depending on the source. In the United States, most physicians use the criteria for diagnosing metabolic syndrome included in the ATP III guidelines. These guidelines were developed by the National Heart, Lung & Blood Institute (NHLBI) as part of its National Cholesterol Education Program (NCEP). People with any three of the risk factors in the criteria are considered to have metabolic syndrome.

A market waiting for a drug

The number of people who may have metabolic syndrome varies between one in four and one in five Americans, depending on the source. Cambridge Healthtech Advisors (CHA), a market research company, reports that about 25% of Americans aged 20 to 70 years may have metabolic syndrome, and this figure may be closer to 50% in the elderly. Another market research firm, Decision Resources, estimates the market for metabolic syndrome drugs will reach at least $13 billion by 2013.

CHA also reported that while there are plenty of drugs available to treat different aspects of the syndrome, there are no single agents available, nor has a "safe and highly effective" combination been identified. Therefore, CHA concluded that metabolic syndrome represents an unmet need in the pharmaceutical market.

Coming down the pipeline

The pharmaceutical industry has been furiously working to find the magic bullet that will put the brakes on obesity. Some researchers have set their sights a bit higher, aiming for a wonder drug that could treat all or most of the metabolic syndrome risk factors.

Arguably the drug receiving the most attention so far has been rimonabant (Acomplia, Sanofi-Aventis). Widely anticipated as the first single-drug regimen to treat metabolic syndrome, rimonabant is the first in a new class of drugs called selective cannabinoid type 1 (CB1) antagonists. These drugs block the same receptors that stimulate appetite in marijuana smokers. In clinical trials, rimonabant has had minimal effect on weight loss (an average of only four to 11 lb. after two years of treatment). However, rimonabant has had impressive results in other areas. Waist circumference was decreased twice as much as with placebo. Triglycerides were lower and HDL levels were higher in treated patients versus those on placebo. Insulin resistance was lowered, and hemoglobin A1c levels were significantly reduced.

Starting with an average A1c baseline of 7.3, just over 52% of patients in the rimonabant group lowered their A1c below 7, and 43% got it below 6.5. This figure is particularly important, because getting A1c below 6.5 has proven difficult for most patients. In fact, the American Association of Clinical Endocrinologists reported in May that two-thirds of Americans with Type 2 diabetes have failed to meet this goal.