A resident in your clinic is following a 45 y/o obese female patient (BW - 93kg, BMI 39 kg/m2) with several concurrent medical problems (type II diabetes, HTN, ostearthritis). She's tried a low calorie diet with limited success for the last couple months. The resident wants to give this patient the best chance of successful weight loss. Since the two currently available prescription weight loss medications work by different mechanisms, he plans of starting the patient on both while continuing a low calorie diet.

Do you concur with the resident? Why or why not.

Probably not. Even though the two commercially available weight loss agents, sibutramine and orlistat, work by different mechanisms, at least one small study (n=34 women) did not show further weight loss with the combination compared to sibutramine alone. Keep in mind the small study size when interpreting the results and/or trying to extrapolate the results to a broader population. Future research may(?) show different results.

Remember, patient response to drug therapy for weight loss is highly variable. Drug therapy MUST (repeat MUST!) be used in conjunction with lowered calorie intake and increased energy expenditure (exercise or physical activity). If a drug is not effective after 4 weeks, discontinuation of the drug should be considered.

The approach to obesity and weight loss is far too large to address completely here but let me try to stress a couple of key points.

Target or weight loss goal - patients should NOT try to achieve their "ideal body weight". Recent information shows that a 10% weight loss that is sustained (sustained is the KEY!!) is enough to significantly benefit the health of the patient. Many patients can achieve this weight loss but keeping the weight of is truly a lifelong endeavor. Weight cycling (frequent weight fluctuations up and down usually from on and off dieting) has been associated in several studies with increased mortality. A reasonable rate of weight loss should be about 1 to 1.5 pounds per week. The NIH and National Academy of Sciences recognizes a 5% weight reduction maintained for 1 year as "successful".

When to use pharmacotherapy - many sources recommend pharmacotherapy for weight loss when the body mass index (BMI) is > 30 kg/m2. The BMI is calculated by dividing the body weight in KG by the square of the height in meters. Pharmacotherapy should also be considered in patients with a BMI of > 25 to 27 kg/m2 if the patient has 2 or more additional risks factors such as hyperlipidemia, HTN, type II diabetes, h/o or cardiovascular disease, sleep apnea, etc.

Low calorie diets - reducing the daily calorie intake by 500-1,000 calories a day should result in a weight loss of about 1-2 pounds a week. A reduction of 300-500 calories a week should cause a 0.5-1.0 pound weight loss per week. Advise patients that a calorie is a calorie is a calorie regardless of where it comes from (protein, carbohydrate, fat). Very low calorie diets are effective in causing weight loss but are difficult to maintain and are generally not recommended.

Physical activity - this is an important part of any weight loss program. Besides helping lose weight and boosting metabolic rate, there are other health benefits (cardiovascular, mental health, stress relief, etc). Goal should be 30-45 minutes a day 3-5 days a week.

Behavior modification - just like any other 'addiction', behavior modification is a must for successful long-term weight loss. Patient preference will help determine which method of behavior modification will work best whether that is one-on-one sessions or group meetings such as Weight Watchers.

Surgery - these methods can be very effective and weight loss results significant. Surgery is not without risks and surgery for weight loss should only be considered in patients with a BMI of > 40 kg/m2 who have failed less-severe, less-invasive interventions and are suffering from obesity-related complications.

Herbal remedies - generally not recommended. Ephedra or Ma Huang can cause significant toxicities, esp. in large doses or in patients with cardiovascular disease.

Future therapies - a lot of research is directed at weight loss. Some therapies under consideration include leptin and leptin analogues. Leptin is manufactured by adipose tissue and decreases food intake. Currently, leptin must be administered SQ. Neuropeptide Y (NPY) antagonists - blocks the very potent appetite stimulant effects of NPY. Beta 3 agonists - beta 3 receptors are thought to be involved with lipolysis and thermogenessis through burning of fat in adipose tissue. Cholecystokinin decreases food intake by decreasing gastric emptying. Poor oral bioavailability and a short life have prompted the search for an oral analogue.

        Bottom line - There is NO magic bullet!!!

Academically, weight loss is a very simple equation - you have to spend MORE calories than you take in. Making this happen in real life and maintaining the loss is a significant lifelong endeavor. Weight loss should start with a reasonable goal (5-10% weigh loss). It should be a multidisciplinary approach including low calorie diet, increased physical activity, and behavior modification. Pharmacotherapy may be part of the equation in selected patients.

References -

- Wadden TA et al. Effects of sibutramine plus orlistat on obese women following one year of treatment by sibutramine alone: 1 placebo-controlled trial. Obesity Research. 2000;8:4331-7.

- Bray GA, et al. Medicinal strategies in the treatment of obesity. Nature 2000;404:672-7.