What role for weight-loss medication?

Weighing the pros and cons for obese patients

Holly R. Wyatt, MD; James O. Hill, PhD

VOL 115 / NO 1 / JANUARY 2004 / POSTGRADUATE MEDICINE

CME learning objectives

• To understand the role of weight-loss medications in long-term treatment of obesity
• To describe the rationale for prescribing long-term use of weight-loss medications in conjunction with lifestyle changes
• To appreciate the amount of weight loss that realistically can be achieved with weight-loss medications in a typical obese patient

Centers for Obesity Research and Education receives or in the past 3 years has received educational grants from Abbott, Aventis, Roche, Bristol-Myers Squibb, Takeda, Slim Fast, Procter and Gamble, and OrthoMcNeil. Dr Wyatt, national program director of C.O.R.E., receives salary support from this funding for obesity-related educational programs. Dr Hill is a principal of C.O.R.E. The authors disclose no unlabeled uses of any product mentioned in this article.

This is the first of two articles on weight management.

Preview: Because of the bad press about weight-loss drugs in recent years, physicians and patients alike may be suspicious of all such medications. However, the agents currently approved for long-term use warrant a second look. For overweight patients who need to lose weight to prevent or lessen the risk of obesity-related disease, these drugs can help achieve medically significant weight loss when used as an adjunct to lifestyle changes. Here, Drs Wyatt and Hill dispel some myths about weight-loss medications and suggest ways to maximize their effectiveness when prescribed in selected patients. Wyatt HR, Hill JO. What role for weight-loss medication? Weighing the pros and cons for obese patients. Postgrad Med 2004;115(1):38-45, 58

Weight-loss medications are not widely prescribed, and physicians have many legitimate reasons to be cautious and skeptical about recommending these drugs for their obese patients. First, weight-loss medications in general have had a history of poor outcomes and "unintended consequences" (1). Past use of the amphetamine-derived addictive stimulants and the unexpected side effects involving heart valves from use of "phen-fen" have not helped to create confidence in the use of weight-loss drugs.

Second, only recently has obesity been recognized as a "legitimate" metabolic disease with both a physiologic and a genetic basis (2). In the past, obesity was thought of as a social condition or a character flaw stemming from laziness or lack of willpower, not a justifiable disease process deserving of medical attention, much less medication. The consensus of the medical profession was that legitimate doctors did not treat obesity.

Third, weight management is just beginning to make its way into the medical school curriculum (3). Consequently, the majority of currently practicing physicians likely did not receive formal medical training in obesity. Rather, they have had to acquire their own information about the rationale for treating obesity and about the therapeutic options available. Fortunately, this situation is slowly changing, and weight management is becoming an important part of medical school and residency training.

Advances in weight management

The severe impact of obesity on overall morbidity and mortality is indisputable. Primary care physicians can expect that more than half of their patients will have weight issues that potentially contribute to suboptimum health. Currently, more than 60% of the US population is either overweight (ie, body mass index [BMI], 25.0 to 29.9 kg/m²) or obese (ie, BMI, >30 kg/m²) (4).

Most physicians realize the necessity of addressing weight issues with their patients, and there is rising demand for better tools and strategies for managing weight. Recent research has greatly expanded the understanding of obesity as a genetic, physiologic disease that manifests itself in an environment where physical activity levels are low and caloric intake potential is high (5). Today evidence-based guidelines are available to guide physicians in obesity management, including the appropriate use of medications (6).

At present, there are safe and effective weight-loss medications that, when prescribed appropriately, are not associated with any of the adverse health-related outcomes of earlier agents. Although more effective medications presumably will be developed over time, the current agents can produce sufficient weight loss to significantly improve health and decrease the risk of many chronic diseases. The understanding is growing that chronic incurable diseases, including obesity, require long-term use of medication. For the first time, many physicians are receiving training about the treatment of obesity, a disease that affects about one third of the US population (4) and deserves serious medical attention.

Three myths about weight-loss medications

Why should physicians prescribe weight-loss medications for treatment of obesity? Perhaps a better way to address this question is to consider the converse: Why shouldn't physicians prescribe medications when necessary to treat obesity?

MYTH NO. 1. Obesity is a lifestyle problem; therefore, medications are not necessary.
The data suggest that this is not the case and that lifestyle changes alone do not solve the problem for all patients. As mentioned, obesity has a definite physiologic and genetic basis that is expressed as excessive weight in an environment of low energy expenditure and high energy intake (7,8). Research has clearly shown that individual differences in physiology impact body weight and may affect how much weight is gained or lost under specific lifestyle conditions (9). It may be more difficult for some individuals to lose weight and maintain the loss than for others.

Medications are routinely used to treat metabolic diseases such as diabetes, hypertension, and hyperlipidemia. As with obesity, individual physiologic differences affect the risk of diabetes as well as treatment of the disease. Despite this similarity, many physicians who routinely prescribe diabetes medications do not think obesity needs medication treatment. The old perception that obesity is not a real medical issue or somehow does not deserve medication may remain in the back of the mind of many physicians (10).

Long-term changes in dietary and physical activity patterns likely could completely treat obesity in many patients. Interestingly, such changes also could effectively treat type 2 diabetes, hypertension, and hyperlipidemia in many patients. However, the reality is that long-term lifestyle changes are difficult for most people, and medications are given as an adjunct to lifestyle interventions. This is a familiar concept to physicians who accept this model for most chronic disease states.

For example, although diet and exercise alone could effectively control type 2 diabetes in many patients, physicians rarely insist that lifestyle change be the only treatment used for long-term control of blood glucose levels. They know that long-term lifestyle changes, while possible for some patients, do not occur in the majority of patients; therefore, diabetes medication is routinely prescribed as an adjunctive treatment. Do some diabetic patients live a lifestyle that makes their diabetes much harder to treat? This is absolutely true, but lifestyle change is rarely the only intervention that is offered to those patients. Thus, the role and rationale for use of medications to treat obesity are very similar to those in other chronic diseases requiring adjunctive drug therapy when diet and physical activity have not been successful.

MYTH NO. 2. Taking weight-loss medications is too risky.
All medications involve some degree of risk, and weight-loss medications are no exception. As with any other disease that can be treated with medication, physicians must decide which obese patients to treat. Generally, the health risks of obesity increase as the BMI increases (11). This relationship between health risks and BMI is the reason why the evidence-based guidelines for obesity treatment established by the National Heart, Lung, and Blood Institute (NHLBI) recommend that weight-loss medications be considered in patients with a BMI of 30 kg/m² or higher and in those with a BMI of 27 kg/m² or higher who have an obesity-related comorbid illness (6) (table 1).

Although weight-loss medications carry some measurable degree of risk, a BMI of 30 kg/m² or higher also carries a significant health risk, and it is generally thought that successful weight reduction will produce a benefit that is worth the medication risk. Persons with obesity-related comorbidities (eg, hypertension, diabetes, dyslipidemia, sleep apnea, heart disease) are at even higher risk from excessive weight. Therefore, the NHLBI as well as the US Food and Drug Administration (FDA) have changed the guidelines for potential use of weight-loss medication to include patients with a BMI as low as 27 kg/m² (6). Similarly, surgery for obesity may be considered in patients with a BMI of 40 kg/m² or higher. Because the risk associated with surgery is greater than the risk with medication, a higher BMI cutoff was specified in the guidelines to balance the risk ratio (6). In contrast, in patients with a BMI lower than 25 kg/m², the risk of the medication outweighs any benefit because such patients are not at great risk medically from their current weight.

The risk of a treatment method becomes acceptable when the risk of not treating a condition outweighs the risk of the treatment. The risk-benefit ratio model is not unique to obesity but, rather, is commonly a part of decision making in medicine. One role of obesity medication is to decrease the risk of development of health-related complications due to obesity or to make treatment of existing comorbidities easier and more effective.

MYTH NO. 3. Weight-loss medications do not produce enough weight loss to make them a useful treatment option.
Successful short-term weight loss is fairly common and can be achieved with a number of interventions (12,13). However, the ultimate goal in obesity management is long-term weight loss. Maintaining weight loss for longer than 1 year is difficult to achieve routinely, probably because of both physiologic and behavioral adaptations to the intervention. There is some evidence to suggest that physiologic processes which make regaining weight more likely may come into play after a short-term weight reduction (14). Such processes include a drop in metabolic rate, an increase in appetite, and a strengthening in preference for high-energy foods (14). These types of physiologic processes would discourage energy balance after weight reduction and increase the likelihood of a positive energy balance. Thus, physiologically, the body may "fight against" the weight reduction.

In addition, some evidence suggests that continuing the behavioral interventions responsible for short-term weight reduction may be difficult for many people over time in the current environment. For example, a person may lose weight by eating a very-low-calorie diet (ie, 1,000 kcal) and exercising 2 hours a day. This diet and exercise pattern is very different from his or her eating and activity levels before the weight loss. Most people find it extremely difficult to maintain such behaviors over long periods and ultimately return to their previous eating and activity levels and, thus, previous body weight. A major contributing factor to this difficulty is the current environment, in which people are constantly being prompted to eat more and move less in response to large serving sizes of great-tasting, inexpensive food as well as advances in technology that encourage sedentary lifestyles (7).

Weight-loss medications are a tool to help combat these physiologic and behavioral pressures over the long term. Use of sibutramine hydrochloride (Meridia) and orlistat (Xenical), the two weight-loss drugs that are approved by the FDA for long-term use, can make it easier for patients to adhere to lifestyle changes for longer periods. For example, sibutramine decreases appetite, which makes eating fewer calories easier over time. Orlistat blocks one third of the dietary fat consumed, thereby easing some of the pressure on patients to watch how much fat they eat. These medications can help some patients be more successful in losing weight and maintaining the loss.

This effect can be seen in the categorical data from long-term clinical trials of sibutramine and orlistat (12,15) (table 2). Most physicians mistakenly focus only on the average amount of weight loss a medication can produce in a short-term clinical trial. However, the critical result is how many patients can reach the medical goal of 5% to 10% weight loss and maintain it over the long term. At 2 years in the Sibutramine Trial of Obesity Reduction and Maintenance (16), 69% of patients receiving sibutramine treatment were maintaining a significant weight reduction of 5% or higher and 46% were maintaining a 10% or higher reduction, compared with 44% and 21%, respectively, of patients receiving placebo. The role of weight-loss medications is to maximize the number of patients who are succeeding at maintaining a medically significant weight reduction on a long-term basis. These data allow physicians to estimate how many of their patients potentially could reach a significant long-term weight reduction using the medication as an adjunct to lifestyle change.

Key concepts in prescribing a weight-loss drug

To maximize the effectiveness of weight-loss medication, several key concepts should be kept in mind and communicated to patients before initiation of treatment.

Realistic weight-loss expectations
One of the greatest challenges in medical management of obesity is to communicate to patients the amount of weight loss that can be realistically expected from any weight management intervention. Most patients come to their physician with unrealistic expectations. When asked, they usually report wanting to lose 30% of their initial body weight (17). This degree of weight loss is not currently achievable by most patients except perhaps with restrictive gastric surgery.

However, weight-loss medications can help many obese patients achieve a medically significant reduction. A 5% to 10% weight loss can improve hypertension, lipid levels, and blood glucose levels and can prevent health-related complications of obesity (18). Weight-loss goals should be discussed with the patient and realistic expectations established as early as possible. It is also important to focus on nonweight outcomes, to discuss the potential for physiologic limits, and to be empathetic (19). One approach is to set an initial goal of 10% weight loss with the idea that a second goal can be set when the first one is achieved. Long-term maintenance of a 10% weight loss should be seen as success by both the physician and the patient.

Importance of long-term use
For maximum effectiveness, use of weight-loss medications and obesity treatment in general must be thought of as long-term therapy. As with medications for diabetes and hypertension, the benefits from weight-loss medications disappear when the treatment is discontinued. This need for long-term treatment should be discussed with the patient. Obesity is a chronic metabolic disorder, and in most cases, medications need to be taken as an adjunct to lifestyle change as long as the patient wants to maintain the reduction in body weight.

Adjunct to lifestyle change
Another fundamental concept to communicate to patients is the importance of the interaction between drug and behavior (20,21). For weight-loss drugs to work, the pharmacologic action must be translated into behavior. For example, a sense of decreased hunger should result in smaller meals or fewer snacks. Failure to act on such signals results in little or no weight loss.

The current weight-loss medications work best when combined with a specific plan to alter lifestyle behaviors, such as reducing intake and increasing physical activity (21). These medications are not designed to work alone; rather, they maximize the patient's efforts to lose weight. When there is little or no planned effort, there is little to maximize. If the patient has a plan to reduce portions at each meal, the medication will help make it easier to do this, but it will not have much effect if he or she does not actually eat less. Therefore, obesity medications should be prescribed as an adjunct to, not a substitute for, lifestyle change.

Summary

Obesity is a chronic medical disorder that is not going away anytime soon. Physicians need all the education, tools, and resources possible to successfully help their overweight and obese patients. Weight-loss medications alone are clearly not the answer. However, they are one tool physicians can use in combination with lifestyle changes to increase the success of long-term weight loss in selected patients.

References

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12. The practical guide: identification, evaluation, and treatment of overweight and obesity in adults. Rockville, Md: US Dept of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute, North American Association for the Study of Obesity, 2000; NIH publication 00-4084
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17. Foster GD, Wadden TA, Vogt RA, et al. What is a reasonable weight loss? Patients' expectations and evaluations of obesity treatment outcomes. J Consult Clin Psychol 1997;65(1):79-85
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Dr Wyatt is assistant professor, division of endocrinology, diabetes, and metabolism, University of Colorado School of Medicine, and program director, Centers for Obesity Research and Education, Denver. Dr Hill is professor, department of pediatrics and medicine, and director, Center for Human Nutrition, University of Colorado School of Medicine. Correspondence: Holly R. Wyatt, MD, 4200 E Ninth Ave, Campus Box C263, Denver, CO 80262. E-mail: holly.wyatt@uchsc.edu.

Symposium Index

• WHAT ROLE FOR WEIGHT-LOSS MEDICATION?: Weighing the pros and cons for obese patients. By Holly R. Wyatt, MD, James O. Hill, PhD
• BARIATRIC SURGERY: For the right patient, procedure can be effective. By Rebecca Mattison, MD, Michael D. Jensen, MD
• Clinical Commentary. TACKLING OBESITY IN A 15-MINUTE OFFICE VISIT: Physicians can start patients on an effective weight-loss program, despite time constraints. By Donald D. Hensrud, MD, MPH

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