Obesity-news.com THE LATEST IN OBESITY RESEARCH AND WEIGHTLOSS DRUG DEVELOPMENT     Join our list More information      Weintraub study What follows is a summary and then questions and answers pertaining to a long-term weight control study involving medications, conducted by Dr. Michael Weintraub of the University of Rochester School of Medicine and Dentistry. We hope this information is useful to you. First, Some Background on Our Long-Term Weight Control Study A four-year (210 week) study conducted at the University of Rochester School of Medicine and Dentistry and Strong Memorial Hospital has concluded that a combination of two prescribed appetite suppressants is valuable in helping seriously obese people lose weight and maintain that weight loss. The medications -- fenfluramine and phentermine -- were taken together and were part of a weight loss strategy that also included behavior modification, caloric restriction (dieting), and exercise. The medications appear to be safe and effective for longer term use, were not abused, and had few unmanageable side-effects. These results are reported in a series of articles in the May 1992 issue of "Clinical Pharmacology and Therapeutics" by Michael Weintraub, M.D., associate professor of community and preventive medicine, of pharmacology, and medicine at the University of Rochester (N.Y.) School of Medicine and Dentistry. The four-year study was funded by the National Heart, Lung and Blood Institute. Initial Study Initially, 121 participants between 18 and 60 years of age who were from 30% to 80% over their ideal body weights (IBW), were randomly divided into two groups: a medication group (which took the active medication) and a placebo group (which took tablets and capsules with no active medication). After 34 weeks, the group taking the active medication lost, on average, 15.9 per cent of their initial weight; the placebo group lost 4.6 per cent. In terms of pounds, the placebo group did well, losing on average 9 lbs., although the average loss on medication was approximately 32 lbs. Some participants on medication lost more. It is important to stress that ALL study participants began a program of exercise, dieting, and behavior modification before beginning the medications. They continued to exercise and eat appropriately throughout the entire four-year study. Continuous vs. Intermittent Dosing Between weeks 34 and 104 of the study, Dr. Weintraub looked at different schemes for administering the two medications -- continuously, intermittently (stopping and starting), and on a slightly increased dose -- in BOTH the original medicated group and the placebo group. Of particular note is that the placebo group, when placed on active medication, showed very good results; the medications helped the placebo group "catch up" to the medicated group in pounds lost. Also, the physicians concluded that continuous medication seems superior to intermittent (stopping and starting) therapy because the intermittent group experienced more side effects (primarily dry mouth) when the medications were restarted. There was also some weight gain during the periods without medication. Dose Adjustment During weeks 104 to 156, the doctors looked at the effects of different doses of the two medications. They thought that by adjusting the doses, they could achieve a new round of weight loss. Yet, of those increasing the dose of fenfluramine or phentermine or both, 11 lost weight, six did not change, and 19 gained weight. A Second Look at Effectiveness Weeks 156 to 190 of the study compared the initial doses of the two medications to determine if the medications continued to be effective even after three years of continuous therapy. Participants in both groups gained weight, but those receiving active medication gained significantly less. Going Off Medication During the last 20 weeks of the study (weeks 190 to 210), all study participants stopped taking the medications but continued to exercise and watch what and how they ate. By week 210, most of the participants regained the weight they had lost. Without the medications, almost all study participants had difficulty keeping their lost weight off. What Were the Medications and Dosages The medications were fenfluramine hydrochloride (Pondimin extended release; manufactured by A.H. Robins of Richmond, Va.) and phentermine resin (Ionamin; manufactured by Fisons, Rochester, N.Y.). Both medications are approved by the Food and Drug Administration as appetite suppressants. THE MEDICATIONS ARE AVAILABLE ONLY BY PRESCRIPTION. Physicians are encouraged to refer to their Physicians Desk Reference (PDR) and other reference sources for details about these medications. The doses that proved to be effective -- 60 mg of fenfluramine and 15 mg of phentermine -- are lower than the doses of these drugs when given individually (typically, up to 120 mg of fenfluramine and 30 mg of phentermine). Important Note to Patients and Physicians Regarding Dosage and Duration of Treatment Fenfluramine (Pondimin) is NOT available in the extended-release tablet used in the study. While the extended-release form was approved by the FDA, it has not been put on the market by A.H. Robins. However, physicians can consider prescribing 10 or 20 mg tablets of immediate release fenfluramine, which is available, along with phentermine (Ionamin), as follows: a. Start patients on 15 mg phentermine after breakfast and 10 or 20 mg of immediate release fenfluramine one hour before the evening meal. Allow patients a week or two to get used to the medications and their possible side effects. Most unpleasant effects decrease or disappear within several weeks. b. If the patient needs more medication, add 10 to 20 mg fenfluramine to the 15 mg phentermine after breakfast; continue with 20 mg fenfluramine before the evening meal. Unpleasant effects may reappear temporarily. c. Continue 20 mg fenfluramine and 15 mg phentermine after breakfast; increase the dose of fenfluramine before the evening meal to 40 mg, as clinically indicated. Phentermine is also available as Fastin, by other trade names, and generically. Another Note to Physicians The use of fenfluramine and phentermine together and for a long duration is a new and somewhat non-traditional therapy for obesity. You may wish to ask patients to sign a consent form indicating that they fully understand the "newness" of this therapy. Those doctors affiliated with hospital or medical schools can check with their institutional review board (IRB), which can offer guidance on the non-traditional use of FDA-approved medications. How Do These Medications Work? Fenfluramine and phentermine are appetite suppressants, and have been available as FDA-approved prescription medications for a number of years. They are not "fat pills," as has been mentioned in some of the news media; they do not absorb fat or block fat from entering the system. They do not alter one's genetic make-up, which may be a contributing cause of obesity. Who would benefit from this program? How overweight do I have to be? The people participating in the study were seriously and chronically overweight, weighing on average 54% more than their ideal body weight (in relation to their height according to the 1983 Metropolitan Life tables). Study participants did not have hypertension (high blood pressure), diabetes mellitus, or other diseases. No subjects were taking any long-term medications. If I have high blood pressure or diabetes or another chronic condition, can I still use these medications? Yes, with careful follow-up. Blood pressure goes down with these medications; however, soon after starting phentermine, it may increase temporarily. In adults with diabetes, glucose control may be improved after starting these medications since weight loss improves insulin sensitivity in adult-onset diabetes. Further, the use of fenfluramine leads to decreased blood sugar even if patients don't lose weight. However, WITHOUT CAREFUL PHYSICIAN MONITORING, serious problems can occur with high blood pressure and diabetes mellitus. Are there any medications that, if I am taking them, would prevent me from taking these two diet medications? Will these diet medications interfere with birth control pills or other diet drugs? Phentermine and fenfluramine will not interfere with oral contraceptives. However, adverse interactions may occur with other weight control medications, anti-depressants, and others. Physicians should check EVERY patient's current medications in standard references to see if possible adverse interactions might occur. Patients suffering from migraine headaches and clinically significant depression should not receive fenfluramine. Can I take the medications for more than six or eight weeks, as some physicians and pharmacists have said? Yes. Our study has shown that patients may use these medications for more than three years. The medications appear to be safe and effective for longer term use, were not abused, and had few unmanageable side-effects. Are these medications subject to special prescriptions that are non-renewable? Some state boards of medicine have rules limiting the prescribing of appetite suppressants (anorectic agents) to short periods. In New York State, phentermine and fenfluramine are classified as Schedule IV "controlled substances." Physicians can write a prescription for phentermine and for fenfluramine for 30 days' of medication PLUS five refills; the original and the refills must be used within six months of the original prescription. Phentermine and fenfluramine DO NOT require triplicate prescription forms and are not limited to a single 30-day supply (as are Schedule III medications). In New York, and likely in other states, physicians must be sure their personal DFA number is on their prescription forms. Many other states have similar prescribing guidelines for fenfluramine and phentermine. Patients may want to check with physicians and pharmacists regarding what guidelines are applicable. What kind of diet must be pursued? Caloric restriction was individualized, based on "ideal body weight" and other factors. In the study, food intake ranged from 1500 to 1800 calories per day for men and from 1000 to 1200 calories per day for women. Supplemental vitamins are recommended. Patients should consult a nutritionist or dietician for assistance. What kind of exercise is recommended? The goal during the study was for participants to exercise at least 30 minutes three times a week and to "burn off" 300 calories during each exercise session. Walking, swimming, aerobics, and biking were among the exercises pursued during the study. The emphasis is on a consistent exercise program that is enjoyable and that can be realistically followed. Several exercise activities are recommended, both indoor and outdoor, so patients can have some variety and can have alternatives during inclement weather. In addition to following their exercise programs, patients were encouraged to increase their "activities of daily living": use stairs more often, take longer walks from the parking lot, etc. Every little bit helps! What is behavior modification? Dieticians may work with people trying to control their weight to help alter their behavior regarding food and eating in terms of where, why and how they eat. Behavior modification based on the Johnson and Stalonas system was incorporated into our study. Physicians and nutritionists may want to emphasize issues including eating in social situations, portion size, awareness of bingeing, eating breakfast and eating slowly. Emphasis was placed on starting over again if a person slipped away from any aspect of the program (lower caloric intake, exercise, or behavior modification). Support groups were helpful to the participants in our study. Can the doses be altered? Yes. Physicians can start patients at lower doses and then increase the doses as necessary. They can taper the doses and restart them months or years later, if necessary. However, based on our experience, a continuous dose of 15 mg of phentermine and 60 mg fenfluramine enabled participants to most effectively "get over" any side effects, lose weight, and then maintain that weight loss. What about side effects? The reason for giving lower doses of these two drugs is to minimize side effects. The most common side effect was dry mouth, which in some cases lasted for several months, but the severity and number of complaints decreased after that. Other side effects reported included gastrointestinal complaints such as abdominal pain, nausea, a metallic taste, diarrhea, and constipation; after about four weeks, no further complaints of diarrhea occurred. Central nervous system complaints (drowsiness, sleep disturbances, dizziness, nervousness, and sadness) persisted for about six weeks in some participants but then decreased. A few people complained of irregular or fast heart rate, but these effects also subsided. Overall, most side effects decreased after four weeks, and not all participants taking the medications experienced side effects. However, some experienced side effects throughout the duration of the study. We found no abuse of the medications. The stopping and starting of medications was found to cause excessive side effects, which is why we suggest that continuous use of the medications was more beneficial. How much weight can be lost? Participants experienced most of their weight loss during the first 24 weeks of the study. The average weight of the participants at the beginning of the study was about 207 lbs. By week 34, the average weight loss was 32 lbs for the group receiving active medication, compared to a loss of about 7 lbs. for those not taking the medications. Not everyone in the study lost weight; however, some participants lost more than the 32 lb. average. While the medications proved useful in helping people lose weight, THEY WERE EQUALLY USEFUL IN HELPING PEOPLE MAINTAIN THAT WEIGHT LOSS. During this four-year study, weight loss did not continue indefinitely. Hence, keeping the lost weight off took on more significance as the study progressed. Further, realistic goals should be set. Patients may not be able to lose all the weight they desire because of such factors as genetic make up, which, of course, can not be altered by these two medications. By losing weight slowly and then maintaining that weight loss, patients will look better, feel better, and help prevent the adverse effects of excessive weight. Can I have a copy of the study article? The original 68-page study article, in the May 1992 issue of "Clinical Pharmacology and Therapeutics," will not be useful to the lay person. This summary and Q&A gives patients and their physicians a specific picture of the multimodal program, including the medications, and what to expect. The reprint is no longer available; we have run out of our copies and have no more to mail out to physicians. However, physicians may find copies of the May 1992 issue of "Clinical Pharmacology" in the libraries of large hospitals and medical schools or via computer-accessed data banks (Index Medicus, Current Contents/Life Sciences, Exerpta Medica, BRS/Colleague, and MEDLINE). In addition, physicians may wish to contact the manufacturers for information about these medications: Ionamin -- Fisons of Rochester, N.Y. at (716) 475-9000; Pondimin -- A. H. Robins of Richmond, Va. at (804) 257-2000. For further reading for you and your doctor, refer to two articles in the "New York Times" that in our view are accurate: "Appetite Suppressants Aid Obese" by Gina Kolata, Sunday, July 5, 1992, Section A, page 12, and "Diet Pills Are Returning as Long-Term Medication, Not Just Diet Aids" by Trish Hall, Wednesday, Oct. 14, 1992, Section C, page 6. You can likely find these on microfilm in local libraries. What should I do if I want to try these medications? You must see a physician. Please be aware that only a physician can determine if these medications are appropriate for your particular situation. Can I come to Rochester, NY to see Dr. Weintraub? Is there a program or study now taking place? The study took place several years ago and has been over for some time; there are no plans for another study in Rochester. Dr. Weintraub is a clinical pharmacologist who conducts studies on a variety of drugs; he does not have a private practice. Can the University of Rochester refer me to a physician in my area who will put me on these medications? Unfortunately, we can not, though any physician -- internist or general practitioner, gynecologist, endocrinologist etc. -- can prescribe these medications. If you have a personal physician, approach that doctor first. If your doctor is opposed to the use of medications to assist in weight loss, you might want to find a doctor who will consider them. To find such doctors, contact area hospitals, a medical school (if you live near one), and/or the city/county/state medical society. The use of these two medications as part of a weight control plan is fairly new and many doctors are not yet familiar with them, so you may have to do some calling to find a doctor who can prescribe and monitor this therapy appropriately. A Final Note to All Exercise, changing what you eat, and behavior modification are integral parts of the program and must be actively pursued. The medications alone are not the sole answer, though they will help most people who follow the entire program. Good luck!!! References Long-term weight control: the National Heart, Lung, and Blood Institute funded multimodal intervention study. Weintraub M. (medline) Clin Pharmacol Ther. 1992 May;51(5):581-5. 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. Weintraub M, et al. (medline) Clin Pharmacol Ther. 1992 May;51(5):586-94. Long-term weight control study. II (weeks 34 to 104). An open-label study of continuous fenfluramine plus phentermine versus targeted intermittent medication as adjuncts to behavior modification, caloric restriction, and exercise. Weintraub M, et al. (medline) Clin Pharmacol Ther. 1992 May;51(5):595-601. Long-term weight control study. III (weeks 104 to 156). An open-label study of dose adjustment of fenfluramine and phentermine. Weintraub M, et al. (medline) Clin Pharmacol Ther. 1992 May;51(5):602-7. Long-term weight control study. IV (weeks 156 to 190). The second double-blind phase. Weintraub M, et al. (medline) Clin Pharmacol Ther. 1992 May;51(5):608-14. Long-term weight control study. V (weeks 190 to 210). Follow-up of participants after cessation of medication. (medline) Clin Pharmacol Ther. 1992 May;51(5):615-8. Long-term weight control study. VI. Individual participant response patterns. Weintraub M, et al. (medline) Clin Pharmacol Ther. 1992 May;51(5):619-33. Long-term weight control study. VII (weeks 0 to 210). Serum lipid changes. Weintraub M, et al. (medline) Clin Pharmacol Ther. 1992 May;51(5):634-41. Long-term weight control study: conclusions. Weintraub M. (medline) Clin Pharmacol Ther. 1992 May;51(5):642-6. A double-blind clinical trial in weight control. Use of fenfluramine and phentermine alone and in combination. Weintraub M, et al. (medline) Arch Intern Med. 1984 Jun;144(6):1143-8. Home|Subscribe|Archives|Drug info|Contact|Media & Links|Site index|FAQs|Doctors/meetings|Admin Obesity-news is a publication of Hirsch Communications. An on-line subscription is $104.00 per year, payable in advance by check, money order, American Express, VISA or Mastercard. Subscribing is simple using our secure on-line subscription form. 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