Current issues of ACP Journal Club are published in Annals of Internal Medicine


Anorexiant medications enhanced weight-loss programs

ACP J Club. 1992 Sept-Oct;117:47. doi:10.7326/ACPJC-1992-117-2-047

Source Citation

Weintraub M, Sundaresan PR, Madan M, et al. Long-term weight control study I (weeks 0 to 34). The enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo. Clin Pharmacol Ther. 1992 May;51:586-94.



To determine whether the addition of fenfluramine and phentermine to a comprehensive weight-loss program will increase and sustain weight loss.


34-week, randomized, double-blind, placebo-controlled trial.


Research clinic.


550 people volunteered for the study after media advertising. 121 (73% women, 98% white) were eligible because they were 130% to 180% of ideal body weight for height (1983 Metropolitan Life tables), 18 to 60 years old, and free of other diseases including hypertension, diabetes mellitus, or a history of substance abuse.


All participants attended 6 weekly sessions of behavior modification (technical and psychological support, discussion groups, and printed material), dietary counseling, and instruction before randomization. 58 participants were randomized to fenfluramine hydrochloride, 60 mg, and phentermine resin, 15 mg, each morning after breakfast and 54 received matching placebos. All participants had reduced caloric diets (18 to 20 kcal/kg ideal body weight), ongoing behavior modification sessions, and individualized, graded exercise programs. 93% completed the study.

Main outcome measures

Participants saw their own study physician at regular intervals (2 to 4 wk for 10 visits) to measure weight and compliance and for physical evaluations. Questionnaires were completed to assess adverse effects and measure program perceptions.

Main results

At 34 weeks mean weight loss was 14.3 kg for participants in the active treatment group and 4.6 kg for those in the placebo group (P < 0.001). Body mass index fell from a mean of 33.5 to 28.2 for active treatment participants and from 33.4 to 31.0 for those in the placebo group. Participants felt that placebo neither helped nor hindered their program, whereas fenfluramine and phentermine were rated as being very helpful. Adverse effects in both groups were dry mouth, fatigue, and gastrointestinal and central nervous system complaints. 289 adverse effects were reported in the active treatment group and 86 in the placebo group.


Participants receiving fenfluramine and phentermine in addition to behavior therapy, exercise, and a reduced-calorie diet lost more weight than those in an identical program who were not taking active anorexiant medication.

Source of funding: National Institutes of Health.

Address for article reprint: Dr. M. Weintraub, Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA .


Anorexiant medications may accelerate weight loss when used as ancillary therapy, but most studies in this area have suffered from inadequate numbers, noncomparable treatment and control groups, or failure to assess medications as an adjunct to behavior modification, diet, and exercise.

Weintraub and colleagues have addressed several of these methodologic issues well. In a highly selected group of obese individuals, they showed convincingly that anorexiant medications accelerate weight loss. The increased weight reduction in patients taking anorexiant medications was clinically important. Because patients taking active medication had more adverse reactions (77% of side effects) and were more satisfied with their weight loss, a check on blinding would have been useful.

The question of "long-term weight control" as indicated in the title remains unanswered. Do the dramatic improvements in weight reduction found in this study compromise long-term effects (1, 2)? Although most weight was regained over 4 years, anorexiant medications appear to have delayed this process in compliant patients (3).

This study confirms that tolerance to such medication and loss of efficacy does not occur (4, 5). Treatment of obesity probably needs to be lifelong. Until long-term studies are done, the routine use of anorexiant medications in weight-loss programs is still questionable.

Wayne B. Jonas, MD
Walter Reed Army Institute of ResearchWashington, DC, USA

Wayne B. Jonas, MD
Walter Reed Army Institute of Research
Washington, DC, USA


1. Stunkard AJ. Bull N Y Acad Med. 1988;64:930.

2. Craighead LW, Stunkard AJ, O'Brien R. Arch Gen Psychiatry. 1981;38:763-8.

3. Weintraub M, Sundaresan PR, Madan M, et al. Long-term weight control studies II to VII (weeks 0 to 210). Clin Pharmacol Ther. 1992 May; 51:595-641.

4. Bray GA, Gray DS. West J Med. 1988;49:555-71.

5. Hudson KD. J R Coll Gen Pract. 1977:27:497-501.