Endocrinology and Metabolism Clinics of North America
MEDICATING THE OBESE PATIENT
Section snippets
CHALLENGES IN MEDICATING FOR OBESITY
Physicians face a challenge in safely navigating the regulatory terrain that exists regarding the use of existing pharmacologic agents for the treatment of obesity. Most of the currently available medications for use in obesity remain controlled substances. They are regulated at both the federal and state level. Physicians must be especially aware of the applicable state regulations because the state classification of an appetite suppressant may be even stricter than federal designation.
Once a
CHANGING ATTITUDES TOWARD MEDICATING FOR OBESITY
Increased understanding of the role of the autonomic nervous system, hormonal systems, food intake systems, and physical activity regulatory systems in effecting body weight and body composition leads to new approaches to treating the disorder of obesity. Knowledge of the mechanisms underlying obesity lends credibility to a pharmacologic approach.4 Recently, the widespread publicity surrounding discoveries in the genetics of obesity captured the attention of scientists and the public and
SELECTING PATIENTS FOR PHARMACOBEHAVIORAL THERAPY
Increased morbidity and mortality are well-known consequences of overweight. The data linking BMI to mortality as derived by insurance companies demonstrates a J-shaped relationship7 as shown in Figure 2. BMI is a commonly used expression of the relationship of height and weight and is derived from the following formula: Severe obesity, usually defined as a BMI of greater than 35, carries a high risk of morbidity and mortality.26 As demonstrated by Figure 2, weight gain above this point
Amphetamines—Historical Notes
Dextroamphetamine was introduced for the treatment of narcolepsy, but the observation that its use was associated with weight loss led to the development of similar compounds for appetite suppression. The 1995 Physician's Desk Reference (PDR) still lists four amphetamines with indications for weight loss. Dextroamphetamine (Dexedrine), combined dextroamphetamine/amphetamine (Biphetamine), and methamphetamine (Desoxyn) are class II agents and are currently used in children with behavioral
Fluoxetine
Fluoxetine was developed for the treatment of depression. It blocks the reuptake of serotonin. Although it does not have an indication for weight loss, fluoxetine at doses of 60 mg per day was demonstrated to produce significantly more weight loss than with placebo in several trials as reviewed by others.5, 13 In one study,10 fluoxetine was more effective than placebo in producing weight loss and resulted in nearly 12 kg of weight loss in 6 months. However, despite continuing the medication,
COMBINATION PHARMACEUTICAL THERAPY
In 1992 Weintraub and co-workers30 demonstrated the feasibility of combining medications to take advantage of pharmacologic and clinical differences when they used fenfluramine and phentermine, a noradrenergic and a serotonergic
medication, in combination. The side-effect profiles of the drugs were complementary. Phentermine tended to cause insomnia, whereas fenfluramine tended to cause drowsiness. Phentermine tended to cause constipation, whereas fenfluramine tended to cause more frequent bowel
MEDICATIONS TO MAINTAIN WEIGHT LOSS FOLLOWING A MODIFIED FAST
Medically supervised very low-calorie diets of 400 to 800 kilocalories per day often use liquid diets and result in approximately 20 kg of weight loss in 12 to 16 weeks.27 The problem with these diets is regain of weight within the first 1 or 2 years after treatment. Both positive12 and negative1 results have been reported in using medications to address the problem of weight regain in these patients. In one study1 of 42 people on a very low-calorie diet, weight regain occurred despite
Sibutramine
Sibutramine, a novel pharmacologic agent, is a specific reuptake inhibitor for both norepinephrine and serotonin. Thus, the drug seems to have an effect on two components which regulate food intake and may have similar advantages to combination therapy. The drug has been demonstrated to produce a dose-dependent decrease in weight in healthy obese subjects.24 Figure 6 shows the dose-response relationship in 173 patients treated at one site in a multicenter trial of sibutramine at doses of 1, 5,
FUTURE DIRECTIONS
The future of medicating the obese patient holds both promise and challenges. There is much to learn. New pharmacologic approaches are exciting, and as we learn more about the mechanistic aspects of obesity and the regulation of body weight and body composition, new approaches for obesity will develop. There is continued interest in finding agents which increase thermogenesis or which are agonist or antagonists to the neuropeptides which regulate food intake or even specific macronutrient
References (32)
- et al.
Fluoxetine's effects on weight loss in obese subjects 1-3
Am J Clin Nutr
(1991) - et al.
Long term weight loss: The effect of pharmacologic agents
Am J Clin Nutr
(1994) Comments on "Long-term weight loss: The effect of pharmacologic agents," by DJ Golstein and JH Potvin
Am J Clin Nutr
(1994)Mortality of severely obese subjects
Am J Clin Nutr
(1992)- et al.
Dexfenfluramine as adjuvant to a low-calorie formula diet in the treatment of obesity: A randomized clinical trial
Int J Obes
(1992) - et al.
The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet: A double blind trial
Int J Obes
(1992) Barriers to the treatment of obesity [editorial]
Ann Intern Med
(1991)Treatment for obesity: A nutrient balance/nutrient partition approach
Nutr Rev
(1991)Use and abuse of appetite-suppressant drugs in the treatment of obesity
Ann Intern Med
(1993)- et al.
Primary pulmonary hypertension and fenfluramine use
Br Heart J
(1993)
Build Study 1979
Serum immunoreactive-leptin concentrations in normal-weight and obese humans
N Engl J Med
Orlistat (RO 18-0647), a lipase inhibitor, in the treatment of human obesity: A multiple dose study
Int J Obes
Drug therapy after very-low-calorie diets
Am J Clin Nutr
Clinical studies with d-fenfluramine
Am J Clin Nutr
Cited by (0)
Address reprint requests to Donna H. Ryan, MD, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808,
- *
From the Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana