QUICKLINKS AND VIEW OPITONS
An interview about weight loss drugs with obesity researcher Dr. George Bray
Tuesday, June 06, 2006 8:10 am Email this article
George Bray, MD, a Harvard-trained physician, is one of the best known figures in obesity research today. He was co-editor of the International Journal of Obesity from its introduction in 1976 until 1992. He was the founder of the North American Association for the Study of Obesity (NAASO) and edited the journal Obesity Research from 1993 to 1997. He was also the President of the International Association for the Study of Obesity. Dr. Bray has authored or edited over 500 books, book chapters and scientific papers. Here is an interview I did with Dr. Bray several years ago.
Hobbs: Do you feel diet drugs are useful in the treatment of obesity?
Bray: Yes, when used appropriately. As Scoville said—Drugs don’t cure obesity, but that is no reason to reject them out of hand. Partial success is clearly better than failure. The idea that obesity drugs are a failure because people regain weight when they stop taking them, can more appropriately be interpreted that medicines don’t work if they are not taken.
Scoville BA. Review of amphetamine-like drugs by the Food and Drug Administration: Clinical data and value judgements. Obesity in perspective. DHEW Publ No (NIH) 75-708, 1975, 441-3.
Phentermine vs ephedrine and caffeine
Hobbs: You have done a meta-analysis of 40 studies comparing various diet pills that was published in JAMA. What did you find?
Bray: We found that phentermine, dexfenfluramine and mazindol were more effective than either ephedrine alone or ephedrine in combination with other ingredients like caffeine, and more effective than phenylpropanolamine or PPA formerly in over-the-counter diet pills like Acutrim and Dexatrim.
Hobbs: How effective is Meridia (sibutramine) compared to other diet drugs?
Bray: Sibutramine [Meridia] causes dose-related weight loss which compares favorably with other diet drugs. Weight loss is maintained as long as the drug is used, but, as expected, weight is regained once treatment is stopped.
Hobbs: How effective is Xenical (orlistat)?
Bray: Patients lose between 5 and 10 percent of their body weight based on published abstracts.
This is comparable to other diet drugs. There have been several long term trials, but none of them have been published yet [at the time of this interview].
The main difference between orlistat and other diet drugs is the side-effect profile.
Orlistat [Xenical] does not affect heart rate or blood pressure as do sympathomimetic drugs such as phentermine, mazindol or sibutramine [Meridia].
On the other hand, the sympathomimetic drugs [such as phentermine] tend to cause constipation, whereas orlistat [Xenical] increases GI activity.
The frequency of side effects with orlistat appears to drop significantly between the first and second year of treatment.
Ranking Diet Drugs
Hobbs: Based on safety and efficacy how would you rank the various diet drugs.
Bray: Diethylpropion [Tenuate], mazindol and phentermine are approved for short term use, and should be used this way.
Sibutramine [Meridia] is approved for use up to one year, and for patients with increased lipids, with diabetes mellitus, or with significant degrees of overweight.
Sibutramine [Meridia] can increase heart rate 2 to 4 beats per minute and cause a small rise in blood pressure, so it should be used with caution in patients with increased blood pressure or cardiac problem.
Phendimetrazine [Bontril] and benzphetamine [Didrex] are Schedule III drugs which are approved for short term use. They would be back-up drugs in my view.
The combination of ephedrine and caffeine has not been evaluated in clinical trials in the United States and has not been reviewed or approved by the FDA. The use of this combination for obesity is an off-label use and should be done with a protocol and consent forms.
Phenylpropanolamine [PPA] causes more modest weight loss than the other drugs listed above. It could be useful as an adjunct in someone needing to lose only a few pounds who was stuck on a plateau.
Naloxone and Naltrexone
Hobbs: Do opioid blockers like naloxone and naltrexone cause weight loss?
Bray: Probably not.
Atkinson showed that naloxone acutely reduced food intake. However, three other studies using long-acting naltrexone in doses ranging from 50 to 300 mg per day for eight weeks found they had no significant effect on weight, except in one study which found an effect in females.
In this 4-month, double-blind, cross-over study Novi (1990) found 9 of 17 patients given 50 mg of naltrexone daily lost 8.8 pounds while taking naltrexone compared to only 2.1 pounds while taking the placebo.
It should also be pointed out that Mitchell (1987) found that 300 mg of naltrexone per day caused liver toxicity.
- Atkinson RL. Naloxone decreases food intake in obese humans. Journal of Clinical Endocrinology and Metabolism, 1982 Jul, 55(1):196-8.
- de Zwaan M, Mitchell JE. Opiate antagonists and eating behavior in humans: a review. Journal of Clinical Pharmacology, 1992 Dec, 32(12):1060-72.
- Maggio CA, Presta E, Bracco EF, Vasselli JR, Kissileff HR, Pfohl DN, Hashim SA. Naltrexone and human eating behavior: a dose-ranging inpatient trial in moderately obese men. Brain Research Bulletin, 1985 Jun, 14(6):657-61.
- Mitchell JE, Morley JE, Levine AS, Hatsukami D, Gannon M, Pfohl D. High-dose naltrexone therapy and dietary counseling for obesity. Biological Psychiatry, 1987 Jan, 22(1):35-42.
- Novi RF, Lamberto M, Visconti P, Maurino M, Ardizzone A, Mantovan M, Meluzzi A, Francesetti G, Molinatti GM. [The role of opioid antagonists in the treatment of obesity. Results of a clinical trial with naltrexone]. Minerva Endocrinologica, 1990 Apr-Jun, 15(2):121-3.
Hobbs: Does the alpha-2 blocker yohimbine cause weight loss?
Bray: Maybe, but only in women. Two studies found that it had no effect in males.
Sax (1991) found that 43 mg of yohimbine per day for six months had no effect on weight, BMI, or waist-to-hip ratio in men. And Galitzky (1990) also found yohimbine had no effect on weight in men.
But Kucio (1991) reported that yohimbine increased weight loss in women consuming a diet of 1000 calories per day.
Those given 5 mg of yohimbine four times per day lost 7.8 pounds in three weeks compared to 4.9 pounds in the control group.
- Sax L. Yohimbine does not affect fat distribution in men. International Journal of Obesity, 1991 Sep, 15(9):561-5.
- Galitzky J, Riviere D, Tran MA, Montastruc JL, Berlan M. Pharmacodynamic effects of chronic yohimbine treatment in healthy volunteers. European Journal of Clinical Pharmacology, 1990, 39(5):447-51.
- Kucio C, Jonderko K, Piskorska D. Does yohimbine act as a slimming drug? Israel Journal of Medical Sciences, 1991 Oct, 27(10):550-6.
Questran—the cholesterol-lowering drug cholestyramine
Hobbs: Is the cholesterol-lowering drug cholestyramine (Questran) effective for weight loss? A popular book written several years ago suggested using cholestyramine as a way of reducing fat absorption and causing weight loss.
Bray: No. Cholestyramine does inhibit digestion of fat and increases the amount of fat that is excreted in the stool, but two older studies using doses near the maximum found no significant effect on weight.
- Bray GA. The Obese Patient, 9th edition. Philadelphia: WB Saunders, 1976.
NutraSweet / Aspartame
Hobbs: Does aspartame (NutraSweet) cause weight loss?
Bray: Maybe in women, but not in men.
Kanders (1988) found that women substituting aspartame for sugar lost 16.5 pounds in three months versus 12.8 in the control group. However, in men there was no difference between groups.
- Kanders BS, Lavin PT, Kowalchuk MB, Greenberg I, Blackburn GL. An evaluation of the effect of aspartame on weight loss. Appetite, 1988, 11 Suppl 1:73-84.
Hobbs: Does DHEA cause weight loss?
Bray: No, not in humans. It has been shown to decrease body fat in mice, but not in man. Usiskin (1990) gave obese men 1600 mg for 28 days and found no change in weight, fat or waist-to-hip ratio. One study, however, showed promising results with a derivative of DHEA called etocholandione.
- Usiskin KS, Butterworth S, Clore JN, Arad Y, Ginsberg HN, Blackard WG, Nestler JE. Lack of effect of dehydroepiandrosterone in obese men. International Journal of Obesity, 1990 May, 14(5):457-63.
Fiber / Guar Gum
Hobbs: Do fibers like guar gum cause weight loss?
Bray: Maybe, but maybe not. The results of studies are variable.
Hobbs: Will beta-3 agonists be effective for weight loss?
Bray: Beta-3 agonists cause fat loss in rodents, but so far have not found to be effective in humans. This may be because beta-3 receptors in humans are different than those in mice. In other words, the beta-3 agonists that stimulate beta-3 receptors in mice do not stimulate beta-3 receptors in humans.
Hobbs: Some weight loss clinics still give shots of HCG, human chorionic gonadotropin, for weight loss. Is HCG helpful for weight loss?
Bray: No. Four double-blind studies have shown that HCG has no significant effect on weight.
- Greenway FL, Bray GA. Human chorionic gonadotropin (HCG) in the treatment of obesity: a critical assessment of the Simeons method. Western Journal of Medicine, 1977 Dec, 127(6):461-3.
Glucophage / Metformin
Hobbs: Does metformin (Glucophage) have a place in obesity treatment?
Bray: Metformin is the preferred drug for obese non-insulin-dependent type II diabetics. Whereas the anti-diabetic drugs known as sulfonylureas are usually associated with weight gain, metformin is associated with weight loss. Bailey (1992) reported metformin-associated weight losses ranging from 5 pounds in seven months to 13.2 pounds in two years.
- Bailey CJ. Biguanides and NIDDM. Diabetes Care, 1992 Jun, 15(6):755-72.
Glucocorticoids / Stress Hormones
Hobbs: What is the effect of glucocorticoids, or stress hormones, on obesity?
Bray: People with high circulating levels of glucocorticoids caused by overactive adrenal glands or taking high doses of glucocorticoids have an increase in belly fat as well as increased catabolism, or breakdown, of skin, muscle and bone. The condition is called Cushing’s syndrome. People with low levels of glucocorticoids due to adrenal insufficiency, a condition called Addison’s Disease, tend to have a loss of body fat. Okada, York and I (1992) showed that glucocorticoids are necessary for the development of obesity in animals, and we found that the drug RU-486, sometimes referred to as the abortion pill, which blocks glucocorticoids, prevented mice from gaining weight on a high-fat diet, but had no effect on weight of mice fed low-fat diets. Glucocorticoid-blockers needs to be studied in humans for their effect on weight.
- Bray GA, Fisler JS, York DA. Neuroendocrine control of the development of obesity: understanding gained from studies of experimental animal models. Frontiers Neuroendocrinology, 1990, 11(2):128-81.
- Okada S, York DA, Bray GA. Mifepristone (RU 486), a blocker of type II glucocorticoid and progestin receptors, reverses a dietary form of obesity. Am J Physiol, 1992 Jun, 262(6 Pt 2):R1106-10.
Low Carbohydrate Diets
Hobbs: What do you think about high protein/low carbohydrate diets like THE ZONE, PROTEIN POWER, and THE ATKINS DIET?
Bray: Popular books like The Zone, Protein Power and the Atkins Diet are not peer-reviewed. Because of the first amendment, books can say many things that might not meet the rigors of careful review. I cannot recommend any of them until there is critical peer-reviewed testing of their principles. I prefer a low fat diet and increased exercise.
Why are we getting fatter?
Hobbs: Why do you think Americans are getting fatter?
Bray: Reduced smoking may be one factor. High fat diets, and a sedentary life style associated with watching television may be another.
Fenfluramine Heart Valve Damage
Hobbs: What do you think caused the heart valve damage associated with fenfluramine and dexfenfluramine?
Bray: I don’t know. There was absolutely no evidence, as far as I know, suggesting that anything other than primary pulmonary hypertension as a major risk.
The apparent epidemic of valvular heart disease was a totally unexpected surprise.
The similarity to the valvular lesions found with the carcinoid syndrome and with ergotamine treatment suggests that serotonin may be involved in some unknown way. We need a great deal more information before we will understand this tragic problem.
George A. Bray, MD
Pennington Biomedical Research Center
Louisiana State University
6400 Perkins Road
Baton Rouge, LA 70808
Articles on the same subject can be found here:
On Jun 06, 2006 at 8:31 am DrJ wrote:
. . . . .
Larry - this is a great little interview, and I appreciate you bringing it to my attention. I am a little stunned by the response that reduced smoking is causing the rise in obesity! Suppose it is as logical as many other answers, though.
Please feel free to share your comments about this article.
© Copyright 2003-2021 - Larry Hobbs - All Rights Reserved.