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Metformin (generic Glucophage), a diabetes medication, probably produces better long-term weight loss results than any other medication.  It also helps prevent the development of diabetes.  It's low cost is a very strong plus ($10-$12/month wholesale for 500 mg three times a day breaking 1000 mg tabs in half).  It currently has the best long-term data with sizeable weight loss (16#) being maintained at least four years as long as the medication is continued.  Metformin has also been found to reduce the risk of death.

Bupropion (Wellbutrin), an anti-depressant, and orlistat (Xenical), which inhibits pancreatic lipase and can block 30% of triglyceride hydrolysis, both seem to help obesity at a much higher cost ($110 and $140/month).  They probably don't cause as much weight loss either.  Sibutramine (Meridia), a norepinephrine-serotonin re-uptake inhibitor stimulant, is extremely expensive at $240/month (10 mg. twice a day).  Average one-year weight loss with sibutramine has been 8 pounds.  A two year study with sibutramine showed quite a bit of back-sliding.  Sibutramine also causes an increase in blood pressure and pulse rate, things that have been associated with dying sooner. Other medications are still less impressive in their weight loss or benefit.  

Obese patients should follow my Recommendations for Healthy Living.  It appears especially important that they take magnesium, calcium and vitamin D, since both have been found helpful in preventing diabetes and vitamin D is low in the obese.  In view of the higher rates of breast and uterine cancer in the obese, yogurt should also be consumed on a regular, ideally daily, basis.

5-HTP Might Help: A very small DB study of 19 obese patients for 5 weeks on 8mg/kg/d found 5-HTP decreased food intake and weight with no effect on mood. J Neural Transm 1989;76(2):109-17; Similar results in DB of 25 diabetic for 2 weeks on 750mg/d.  Int J Obes Relat Metab Disord 1998 Jul;22(7):648-54

Axokine Helped in DB: Axokine, a modified ciliary neurotrophic factor, appears to promote weight loss in overweight and obese patients with type 2 diabetes, according to the findings of a 12-week DB, randomized trial of 299 patients.  The average weight loss was only five pounds, so hopefully the effect continues.  It has also been found to help in non-diabetics.  It is in phase III drug development, which means it should be on the market in a year or two at a fairly high price. The study was funded by the manufacturer. NAASO 2003 Annual Meeting: Abstract 100-OR. Presented Oct. 13, 2003 

Bupropion Helped: 6 month controlled study with two dosage groups and one placebo group combined with exercise and diet and counseling for these found 5% weight loss with placebo and 10% with bupropion. After six months off meds, regained 2%. Xenical prevents body from fully absorbing fat and has 4-5% wt loss. Meridia, a stimulant, has 3-4% weight loss. Fenfluramine off market, but phenteramine often used with Paxil. Wellbutrin study funded by manufacturer. Reuters 2/27/02. 327 patients with BMIs of 30-44 without depression were treated in a diet and exercise program and a DB PC study of 300 or 400 mg bupropion. there was a greater than 5% wt loss in 83% of high dose patients, 59% of moderate dose patients, and 46% of placebo patients at 24 weeks. Anderson, Obesity Res 02;10:633, Univ. of Kentucky; Bupropion generic at 400mg/day costs $112/month (Darby 2003)

Bupropion Helps Lose 6#: In a DB PC study of 394 adults with BMIs of 30-44 on 500 kcal diet, the patients on bupropion lost 9# vs. 3# on placebo. Bupropion SR vs. placebo for weight loss in obese patients with depressive symptoms. Obes Res 2002 Oct;10(10):1049-56

Cimetidine Might Help: 50 women and 5 men who had completed a 8 week DB PC trial of cimetidine for weight loss were invited to participate in an open, non-randomized follow-up study of 42 months. 22 volunteers were treated with cimetidine for 8 weeks twice a year, followed a diet restriction and performed regular exercise. In the non-intervention group the subjects had no behavioral treatment. In the intervention group, non-significant reductions in body weight (4 pounds). In the non-intervention group there was a significant increase in body weight (16.5 pounds). Combination of diet, exercise and intermittent treatment of cimetidine on body weight and maintenance of weight loss. A 42 months follow-up study. Birketvedt GS, Thom E, Bernersen B, Florholmen J. University of Tromso, Norway. Med Sci Monit. 2000 Jul-Aug;6(4):699-703.

Cimetidine Helped in Short Study: In a 12-week DB PC study of 400 mg cimetidine three times daily with 43 overweight patients with Type 2 diabetes, those given cimetidine 11 pounds vs. 3 pounds on placebo. Significant decreases in fasting concentrations of blood glucose, HbA1c, plasma insulin, insulin/glucose ratio, plasma triglycerides and a significant increase in plasma high-density lipoprotein cholesterol were observed in the cimetidine group only. Cimetidine reduces weight and improves metabolic control in overweight patients with type 2 diabetes. Stoa-Birketvedt G, Paus PN, Ganss R, Ingebretsen OC, Florholmen J. University of Tromso, Norway. Int J Obes Relat Metab Disord. 1998 Nov;22(11):1041-5

Cimetidine Didn't Help: OIn a DB PC 8-week trial of 60 obese adults, 13 pound weight loss occurred in both group instructed to eat a fixed weight loss diet. Cimetidine suspension as adjuvant to energy restricted diet in treating obesity. Rasmussen MH, Andersen T, Breum L, Gotzsche PC, Hilsted J. Denmark. BMJ. 1993 Apr 24;306(6885):1093-6

Cimetidine Helped: In a 60-patient DB PC 8-week study of cimetidine suspension 200 mg or placebo 30 minutes was given before the three main meals with subjects to follow a diet restricted to 5 MJ/day supplemented with 9 g fibre per day, those on cimetidine lost a mean of 16 pounds more than those given placebo (p < 0.001). Effect of cimetidine suspension on appetite and weight in overweight subjects. Stoa-Birketvedt G. Fjellhamar, Norway. BMJ. 1993 Apr 24;306(6885):1091-3

CLA: Conjugated Linoleic Acid No Help and Harmful: In a 81-patient DB PC 26 week study, the daily consumption of a drinkable dairy product containing up to 3 g of CLA isomers for 18 weeks had no statistically significant effect on body composition in overweight, middle-aged men and women. Effects of two conjugated linoleic Acid isomers on body fat mass in overweight humans. Malpuech-Brugere C, Verboeket-van de Venne WP, Mensink RP, Arnal MA, Morio B, Brandolini M, Saebo A, Lassel TS, Chardigny JM, Sebedio JL, Beaufrere B. Clermont Ferrand, France. Obes Res. 2004 Apr;12(4):591-8. Another DB PC study found CLA increases insulin resistance and states that the use of CLA for weight loss is troubling and likely to increase diabetes. Diabetologia. 2004 May 28

Fluoxetine Helped for 6 Months But Not 1 Year: In a large 438-patient DB PC study of obesity treated with fluoxetine 60 mg/day vs. placebo, patients on fluoxetine had maximum weight loss at 20 weeks and were significantly better at 28-weeks, but not at 1 year. Eli Lilly. Fluoxetine: a randomized clinical trial in the treatment of obesity. Goldstein DJ, Rampey AH Jr, Enas GG, Potvin JH, Fludzinski LA, Levine LR. Int J Obes Relat Metab Disord. 1994 Mar;18(3):129-35; Ed: There are many more fluoxetine studies, but the results are not Earth shaking.

Growth Hormone Injections $$$ Helps Lose 5#: 6 months of nightly GH injections resulted in a 5# greater weight loss. Both groups urged to stay of 500 calorie diet and exercise. Stewart Albert, St. Louis U, Endocrine Society meeting, Phila 6/19/03. This is extremely expensive weight loss.

Growth Hormone Very Expensive Treatment for Adult Obesity: Adult GH deficiency (AGHD) is characterized by an altered body composition, an atherogenic lipid profile, decreased exercise capacity, and diminished quality of life. In a DB PC study of 166 subjects with AGHD, GH-treated men and women (0.0125 mg/kg/day) had small but significant decreases in total body and trunk fat and increases in lean body mass as well as significant improvements in total cholesterol and low-density lipoprotein (P < 0.05 for all). No treatment effects were observed in strength and endurance, quality of life, or bone mineral density. Growth Hormone (GH) Replacement Therapy in Adult-Onset GH Deficiency: Effects on Body Composition in Men and Women in a Double-Blind, Randomized, Placebo-Controlled Trial. Hoffman AR, Kuntze JE, et al. Stanford University. J Clin Endocrinol Metab. 2004 May;89(5):2048-56. Ed: Growth hormone is very expensive. The results of this study are not impressive.

Inositol Helped Polycystic Ovarian Syndrome and Some Weight Loss: In a DB PC trial of 283 women with oligomenorrhea and polycystic ovaries, those receiving inositol (100 mg, twice a day), the time to first ovulation was shorts (24 vs. 42 days) with more frequent ovulations (23% vs. 13% of weeks). Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the inositol group, whereas in the placebo group was recorded an increase of the weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the inositol-treated group. Metabolic risk factor benefits of inositol treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge test was recorded after 14-wk of inositol and placebo therapy. There was an inverse relationship between body mass of the patients and the efficacy of the treatment. These data support a beneficial effect of inositol in improving ovarian function in women with oligomenorrhea and polycystic ovaries. One-third of inositol women dropped out vs. 10% of placebo. Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Gerli S, Mignosa M, Di Renzo GC. University of Perugia, Italy. Eur Rev Med Pharmacol Sci. 2003 Nov-Dec;7(6):151-9

Oxyntomodulin Helped Short-Term Weight Loss: Oxyntomodulin is a 37 amino acid peptide containing the 29 amino acid sequence of glucagon. It was discovered in rats in 1981 to stimulate cAMP in the gut. In a DB PC 4 week study of obese adults, those injecting oxyntomodulin three times a day had weight reduced by 5 pounds vs. 1 pound for placebo (P = 0.0106). There was a reduction in leptin and an increase in adiponectin with a loss of body fat. Energy intake by the treatment group was significantly reduced by 250 kcal (P = 0.0023), with no change in subjective food palatability. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Wynne K, et al. Imperial College Faculty of Medicine, London, U.K. Diabetes. 2005 Aug;54(8):2390-5

Pramlintide Slight Benefit in Diabetics: In a 498-patient 26-week DB PC study of type 2 diabetes, the synthetic amylin analog pramlintide 120 mcg twice a day, which delays gastric emptying, was better that placebo at lowering blood sugars and body weight (4 pounds), although the difference were quite minor. Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Hollander P, Maggs DG, Ruggles JA, Fineman M, Shen L, Kolterman OG, Weyer C. Baylor Univ. Obes Res. 2004 Apr;12(4):661-8


Rimonabant (Acomplia) May be Useful for Weight Loss; Little Value for Smoking: Rimonabant is a member of a new drug class called selective Cannabinoid CB1 Receptor Antagonist. Endogenous (e.g. anandamide) and exogenous (e.g. cannabis) cannabinoids cause hunger particularly for palatable food. In a DB PC study by Jean-Pierre Despres of Laval University, 1,036 subjects with dyslipidemia and a body mass index (BMI) between 27 and 40 kg/m2 received 5 mg or 20 mg of rimonabant or placebo.  While no specific diet was required, patients were told to reduce caloric intake by 600 calories a day and were given nutritional guidance with diets. There was an average weight loss at one year with 20 mg of 19# vs. 5# with placebo. The 5 mg. dose was not significantly better than placebo. In addition, there was a 23% increase in high-density lipoprotein cholesterol, a 15% decrease in triglycerides, a 27% reduction in C-reactive protein, and a favorable change in the composition of cholesterol, with a decrease in the proportion of small, dense low-density lipoprotein cholesterol particles. The most common adverse effect was nausea, which was reported by 15.7% of patients in the 20-mg rimonabant group compared with 9% in the placebo group. The second study also had no peer review and placebo results were not even mentioned on Medscape. Medscape and CNN Money 3/12/04. The manufacturer is also researching it for reducing tobacco and alcohol consumption, although its success against tobacco has been very unimpressive. Lancet. 2005 Apr;365(9468):1389-97.


Topirimate Causes Modest Weight Loss: In a 28-week, DB PC study of 531 obese adults with hypertension, those taking 96 or 192 mg/day of topiramate had weight losses of 5.9%, and 6.5% vs. 1.9% for placebo (p <0.001) and decreases in diastolic BP of 5.5, and 6.3 vs. 2.1 mm Hg (p <0.015 vs placebo). Systolic BP was decreased by 8.6 and 9.7 mm Hg in the 96- and 192-mg groups and 4.9 mm Hg in the placebo group (p = NS). All subjects received a standardized diet, exercise advice, and behavioral modification from run-in through study end. fficacy and safety of topiramate in the treatment of obese subjects with essential hypertension. Tonstad S, et al. University of Oslo, Norway. , Am J Cardiol. 2005 Jul 15;96(2):243-51. Ed: Topirimate is expensive and causes a high rate of side-effects, some serious.  The small benefit of an 8-9 pound weight loss for a 200 pound person means that it is not a first line treatment.  Long-term effects are unknown, but, based on other medication studies, it may lose some of its effectiveness and have to be continued indefinitely to have any benefit at all.

Thomas E. Radecki, M.D., J.D.

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