Weight Management Express Report

Publication date: 2001-12-12

Medical Management of Obesity and Its Related Metabolic Complications

This report was reviewed for medical and scientific accuracy by Stephen H. Schneider, MD, FACP, Professor of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Editorial

Ken Fujioka, M.D., Director, Nutrition & Metabolic Research Center, Scripps Clinic, San Diego, CA

Obesity is a public health problem that is associated with significant morbidity and mortality due to multiple co-morbid diseases including coronary heart disease (CHD), dyslipidemia, congestive heart failure, Type 2 diabetes mellitus, hypertension, osteoarthritis and certain cancers (e.g., endometrial, breast, prostate, and colon).¹ The alarming aspect of obesity is that despite our best efforts, it continues to increase. Over the past 20 years, the percentage of adults with obesity has gone from 15% to 27% and the incidence of children diagnosed as obese has essentially doubled.^2,3 Indeed, each year an estimated 300,000 adults die of causes related to obesity.⁴ Patients with obesity report a significant impairment in quality of life.^5,6,7 As expected, there has been a corresponding increase in the incidence of co-morbid diseases such as diabetes.

Treatment options for obesity have been limited by medications that have been associated with drug-induced medical problems. In 1997, two anti-obesity medications [fenfluramine, dexfenfluramine] were voluntarily withdrawn from the market due to a possible association with cardiac valve abnormalities.⁸ More recently, the Food and Drug Administration (FDA) requested the market withdrawal of phenylpropanolamine due to increased risk of hemorrhagic stroke in certain patients.⁹ As a result, the clinical development of medications for obesity underwent a fundamental and philosophical change. It had become abundantly clear that if millions of obese individuals were possible candidates for a weight loss medication, safety and efficacy would have to be primary parameters in development and regulatory review.

Treatment of obesity has been characterized with many patients successfully losing weight, only to quickly regain the lost weight. Weight loss agents approved in the current era must not only be safe and effective but also show effective improvement of co-morbid diseases. Currently, clinical research on medications for obesity focuses additional attention on associated co-morbidities: diabetes, hypertension, and dyslipidemias. The direct and indirect costs of healthcare associated with diabetes alone were an estimated $98 billion in 1997.¹⁰ By inducing weight loss in a diabetic patient, clinical researchers look to establish a corresponding improvement in significant diabetic parameters such as hemoglobin A_1c (HbA_1c) and quality of life.

In current medical practice, primary care physicians are treating more and more diabetic patients while facing the complexity of multiple medical problems that accompany diabetes. In the primary care and endocrinologists' offices, the diabetic patient is often the most challenging to medically manage.

The following report examines the weight loss drug sibutramine (Meridia, Abbott Labs), a norepinephrine and serotonin reuptake inhibitor,^11,12 particularly its pharmacological effects and therapeutic outcomes in patients with diabetes. It is well known that weight loss is of tremendous clinical benefit to the obese Type 2 diabetic patient. Weight reduction improves insulin sensitivity and carbohydrate metabolism. Therefore, it is critical for the treating physician to understand the clinical consequences and expected metabolic outcomes from prescribing a weight loss medication to the diabetic patient.

Perspective

Obesity and Type 2 diabetes have well-established associations, so much so that many researchers attribute their relationship to overlapping metabolic defects (e.g., hypertension, dyslipidemia, hyperglycemia, and hyperinsulinemia) and a shar