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Weight loss agents

The definition of obesity varies depending on what one reads, but in general, it is a chronic condition defined by an excess amount body fat. A certain amount of body fat is necessary for storing energy, heat insulation, shock absorption, and other functions. The normal amount of body fat (expressed as percentage of body fat) is between 25-30% in women and 18-23% in men. Women with over 30% body fat and men with over 25% body fat are considered obese.
Obesity has reached epidemic proportions in the United States. One in three Americans is obese. Obesity is also increasing rapidly throughout the world, and the incidence of obesity has nearly doubled form 1991 to 1998.
Obesity is not just a cosmetic consideration; it is a dire health dilemma directly harmful to one's health. In the United States, roughly 300,000 deaths per year are directly related to obesity, and more than 80% of these deaths are in patients with a BMI (body mass index, which will be discussed later in this article) over 30. Obesity also increases the risk of developing a number of chronic diseases including:
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Generic name: Orlistat
Manufacturer: Roche (Switzerland)

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RHODIOLA ROSEA
(dry roots)
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28 g
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Preparation of tea: cut fine 5g of Rhodiola rosea roots. 1 cup of boiling water pour in roots and leave for (brew) at least 4 hours. Than filter. Daily dosage: 1/5 cup - 3-5 times per day. For better taste dilute Rhodiola rosea tea with juice, tonic or other herbal tea.

Preparation of tincture for personal usage: Mill 30 g of Rhodiola Rose roots in a coffee-grinder no less than 5-10 mm, add 150 ml of light spirits (30-40%), agitate and steep 3-5 days at room temperature. Separate and filter the extract. Dosage: ? tsp. x 3 times per day.

RHODIOLA ROSEA
(dry extract tablets, total rosavins 40%)

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Dosage: 2 tablets 3 times daily
Course: 30 days, 180 tablets
What Causes Obesity?
The balance between calorie intake and energy expenditure determines a person's weight. If a person eats more calories than he or she burns, the person gains weight (the body will store the excess energy as fat). If a person eats fewer calories than he or she burns, he or she will lose weight. Therefore the most common causes of obesity are overeating and physical inactivity. At present, we know that there are many factors that contribute to obesity, some of which have a genetic component:
Genetics. A person is more likely to develop obesity if one or both parents are obese. Genetics also affect hormones involved in fat regulation. For example, one genetic cause of obesity is leptin deficiency. Leptin is a hormone produced in fat cells, and also in the placenta. Leptin controls weight by signaling the brain to eat less when body fat stores are too high. If, for some reason the body cannot produce enough leptin, or leptin cannot signal the brain to eat less, this control is lost, and obesity occurs. The role of leptin replacement as a treatment for obesity is currently being explored.
Overeating. Overeating leads to weight gain, especially if the diet is high in fat. Foods high in fat or sugar (e.g., fast food, fried food and sweets,) have high energy density (foods that have a lot of calories in small amount of food). Epidemiology studies have shown that diets high in fat contribute to weight gain.
A diet high in simple carbohydrates. The role of carbohydrates in weight gain is not clear. Carbohydrates increase blood glucose levels, which in turn stimulate insulin release by the pancreas, and insulin promotes the growth of fat tissue and can cause weight gain. Some scientists believe that simple carbohydrates (sugars, fructose, desserts, soft drinks, beer, wine, etc.) contribute to weight gain because they are more rapidly absorbed into the blood stream than complex carbohydrates (pasta, brown rice, grains, vegetables, raw fruits, etc.) and thus cause a more pronounced insulin release after meals than complex carbohydrates. This higher insulin release, some scientists believe, contribute to weight gain.
Frequency of eating. The relationship between frequency of eating (how often you eat) and weight is somewhat controversial. There are many reports of overweight people eating less often than people with normal weight. Scientists have observed that people who eat small meals four or five times daily, have lower cholesterol levels and lower and/or more stable blood sugar levels than people who eat less frequently (two or three) large meals daily. One possible explanation is that small frequent meals produce stable insulin levels, whereas large meals cause large spikes of insulin after meals.
Slow metabolism. Women have less muscle than men. Muscle burns more calories than other tissue (which includes fat). As a result, women have a slower metabolism than men, and hence, have a tendency to put on more weight than men, and weight loss is more difficult for women. As we age, we tend to lose muscle and our metabolism slows, therefore, we tend to gain weight as we get older particularly if we do not reduce our daily caloric intake.
Physical inactivity. Sedentary people burn fewer calories than people who are active. The National Health and Examination Survey (NHANES) showed that physical inactivity was strongly correlated with weight gain in both sexes.
Medications. Medications associated with weight gain include certain antidepressants (medications used in treating depression), anti-convulsants (medications used in controlling seizures such as carbamazepine and valproate), diabetes medications (medications used in lowering blood sugar such as insulin, sulfonylureas and thiazolidinediones), certain hormones such as oral contraceptives and most corticosteroids such as Prednisone. Weight gain may also be seen with some high blood pressure medications and antihistamines.
Psychological factors. For some people, emotions influence eating habits. Many people eat excessively in response to emotions such as boredom, sadness, stress or anger. While most overweight people have no more psychological disturbances than normal weight people, about 30 percent of the people who seek treatment for serious weight problems have difficulties with binge eating.
• Diseases such as hypothyroidism, insulin resistance, polycystic ovary syndrome and Cushing's syndrome are also contributors to obesity.
What are the health risks associated with obesity?

Obesity is not just a cosmetic consideration; it is a dire health dilemma directly harmful to one's health. In the United States, roughly 300,000 deaths per year are directly related to obesity, and more than 80% of these deaths are in patients with a BMI (body mass index, which will be discussed later in this article) over 30. Obesity also increases the risk of developing a number of chronic diseases including:
• Insulin Resistance. Insulin is necessary for the transport of blood glucose (sugar) into the cells of muscle and fat (which is then used for energy). By transporting glucose into cells, insulin keeps the blood glucose levels in the normal range. Insulin resistance (IR) is the condition whereby the effectiveness of insulin in transporting glucose (sugar) into cells is diminished. Fat cells are more insulin resistant than muscle cells; therefore, one important cause of IR is obesity. The pancreas initially responds to IR by producing more insulin. As long as the pancreas can produce enough insulin to overcome this resistance, blood glucose levels remain normal. This IR state (characterized by normal blood glucose levels and high insulin levels) can last years. Once the pancreas can no longer keep up with producing high levels of insulin, blood glucose levels begin to rise, resulting in type 2 diabetes, thus IR is a pre-diabetes condition. In fact scientists now believe that the atherosclerosis (hardening of the arteries) associated with diabetes likely develops during this IR period.
• Type 2 (adult-onset) diabetes. The risk of type 2 diabetes increases with the degree and duration of obesity. Type 2 diabetes is associated with central obesity; a person with central obesity has excess fat around his/her waist, so that the body is shaped like an apple.
• High blood pressure (hypertension). Hypertension is common among obese adults. A Norwegian study showed that weight gain tended to increase blood pressure in women more significantly than in men. The risk of developing high blood pressure is also higher in obese people who are apple shaped (central obesity) than in people who are pear shaped (fat distribution mainly in hips and thighs).
• High cholesterol (hypercholesterolemia)
• Stroke (cerebrovascular accident or CVA)
• Heart attack. The Nurses Health Study found that the risk of developing coronary artery disease increased 3 to 4 times in women who had a BMI greater than 29. A Finnish study showed that for every one kilogram (2.2 pounds) increase in body weight, the risk of death from coronary artery disease increased by one percent. In patients who have already had a heart attack, obesity is associated with an increased likelihood of a second heart attack.
• Congestive heart failure
• Cancer. While not conclusively proven, some observational studies have linked obesity to cancer of the colon in men and women, cancer of the rectum and prostate in men, and cancer of the gallbladder and uterus in women. Obesity may also be associated with breast cancer, particularly in postmenopausal women. Fat tissue is important in the production of estrogen, and prolonged exposure to high levels of estrogen increases the risk of breast cancer.
• Gallstones
• Gout and gouty arthritis
• Osteoarthritis (degenerative arthritis) of the knees, hips, and the lower back
• Sleep apnea
• Pickwickian syndrome (obesity, red face, underventilation, and drowsiness)

What can be done about obesity?

All too often, obesity prompts a strenuous diet in the hopes of reaching the "ideal body weight." Some amount of weight loss may be accomplished, but the lost weight usually quickly returns. More than 95% of the people who lose weight regain the weight within five years. It is clear that a more effective, long-lasting treatment for obesity must be found, lest obesity lead to oblivion.

Research articles on Weight loss agents
Diabetes Obes Metab. 2005 Jan;7(1):47-55.
Efficacy and safety comparative evaluation of orlistat and sibutramine treatment in hypertensive obese patients.
Derosa G, Cicero AF, Murdolo G, Piccinni MN, Fogari E, Bertone G, Ciccarelli L, Fogari R.
Department of Internal Medicine and Therapeutics, University of Pavia, 2-27100 Pavia, Italy. giuderosa@tin.it

AIM: The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese hypertensive patients, with a specific attention to cardiovascular effects and to side effects because of this treatment. METHODS: Patients were enrolled, evaluated and followed at three Italian Centres of Internal Medicine. We evaluated 115 obese and hypertensive patients. (55 males and 60 females; 26 males and 29 females, aged 50 +/- 4 with orlistat; 28 males and 30 females, aged 51 +/- 5 with sibutramine). All patients took antihypertensive therapy for at least 6 months before the study. We administered orlistat or sibutramine in a randomized, controlled, double-blind clinical study. We evaluated anthropometric variables, blood pressure and heart rate (HR) during 12 months of this treatment. RESULTS: A total of 113 completed the 4 weeks with controlled energy diet and were randomized to double-blind treatment with orlistat (n = 55) or sibutramine (n = 58). Significant body mass index (BMI) improvement was present after 6 (p < 0.05), 9 (p < 0.02), and 12 (p < 0.01) months in both groups, and body weight (BW) improvement was obtained after 9 (p < 0.05) and 12 (p < 0.02) months in both groups. Significant waist circumference (WC), hip circumference (HC) and waist/hip ratio (W/H ratio) improvement was observed after 12 months (p < 0.05, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05) was present in orlistat group after 12 months. Lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides] reduction (p < 0.05, respectively) was observed in orlistat group and triglyceride reduction (p < 0.05) in sibutramine group after 12 months. No significant change was observed in sibutramine group during the study. No significant HR variation was obtained during the study in both groups. Of the 109 patients who completed the study, 48.1% of patients in the orlistat group and 17.5% of patients in the sibutramine group had side effects (p < 0.05 vs. orlistat group). Side-effect profiles were different in the two treatment groups. All orlistat side effects were gastrointestinal events. Sibutramine caused an increase in blood pressure (both SBP and DBP) in two patients, but it has been controlled by antihypertensive treatment. The vitamin changes were small and all mean vitamin and beta-carotene values stayed within reference ranges. No patients required vitamin supplementation. CONCLUSIONS: Both orlistat and sibutramine are effective on anthropometric variables during the 12-month treatment; in our sample, orlistat has been associated to a mild reduction in blood pressure, while sibutramine assumption has not be associated to any cardiovascular effect and was generically better tolerated than orlistat.

Int J Obes Relat Metab Disord. 2005 Mar 01.
Orlistat in responding obese type 2 diabetic patients: meta-analysis findings and cost-effectiveness as rationales for reimbursement in Sweden and Switzerland.
Ruof J, Golay A, Berne C, Collin C, Lentz J, Maetzel A.
[1] 1Health Services Research Unit, Division of Rheumatology, Center of Internal Medicine, Hannover Medical School, Hannover, Germany [2] 2Global Health Economics Department, Roche Pharmaceuticals, Basel, Switzerland.

OBJECTIVE:: The aim of this study is to review the clinical and economic rationale for the reimbursement of orlistat in responding obese patients with type 2 diabetes. METHODS:: Data from seven randomized controlled clinical trials of orlistat in overweight and obese patients with type 2 diabetes were pooled. A subgroup analysis involving patients who achieved a response (defined as a weight loss of >/=5% after 12 weeks of treatment) was conducted. The outcomes of the pooled analysis were then used to construct a Markov health economic model covering an 11-y period. The incidences of diabetes-related micro- and macrovascular complications were derived from the United Kingdom Prospective Diabetes Study. The effects of changes in body mass index, and the impact of micro- and macrovascular complications on utilities were derived from published sources. Publicly available cost data were used and are presented here in 2001 Euros. Discounting of 3% was applied. A probabilistic sensitivity analysis was conducted to examine the robustness of results. RESULTS:: A total of 1249 patients treated with orlistat and 1230 given placebo were eligible for the intent-to-treat analysis. At the end of the study period, 23% of orlistat patients achieved a weight reduction of >/=5%. These patients showed a mean decrease in HbA1C of 1.16%, a weight reduction of 8.6 kg, a reduction in total cholesterol of 5.3% and a reduction in systolic blood pressure of 5.2 mmHg. The base-case economic analysis revealed costs per quality-adjusted life year gained of \[euro]14 000 in Sweden and \[euro]13 600 in Switzerland. CONCLUSION:: The data presented here support the utilization and reimbursement of orlistat in overweight and obese diabetic patients who respond to the treatment.International Journal of Obesity advance online publication, 1 March 2005; doi:10.1038/sj.ijo.0802925.

Prim Care. 2003 Jun;30(2):427-40.
Orlistat in the treatment of obesity.
Hollander P.
Baylor Hospital, Wadley Tower, Suite 656, 3600 Gaston Avenue, Dallas, TX 75246, USA.

Orlistat has been well studied in several populations, including patients who do and do not have type 2 diabetes and in patients who have impaired glucose tolerance. Overall, modest, but significant, weight loss was seen in all three groups of patients with favorable effects on the comorbidities of obesity. Orlistat has not been associated with a serious adverse event profile, and the mild GI effects that are seen in some patients are well tolerated. In obese patients who do not have diabetes, weight loss is achieved and maintained as shown in the 2-year studies. Moreover, as was well documented in the Swedish multi-morbidity study, favorable treatment effects on the constituents of the metabolic syndrome are seen. Orlistat, together with a hypocaloric diet, was proven to be effective in preventing diabetes in patients who had impaired glucose tolerance. The addition of orlistat resulted in significant weight loss and significance decreases in levels of HbA1c in patients who had type 2 diabetes who were treated with antihyperglycemic drugs. Studies showed that it is possible to identify early which patients may respond best to treatment. Orlistat offers an attractive treatment option for obese patients who do and do not have diabetes and as a combination drug for treatment of obese patients who have type 2 diabetes.

 

Int J Obes Relat Metab Disord. 2002 Feb;26(2):262-73
PPharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials.
Haddock CK, Poston WS, Dill PL, Foreyt JP, Ericsson M.
University of Missouri-Kansas City and Mid America Heart Institute, St Luke's Hospital, Kansas City, Missouri 64110, USA

AIM: This article provides the first comprehensive meta-analysis of randomized clinical trials of medications for obesity. METHOD: Based on stringent inclusionary criteria, a total of 108 studies were included in the final database. Outcomes are presented for comparisons of single and combination drugs to placebo and for comparisons of medications to one another. RESULT: Overall, the medications studied produced medium effect sizes. Four drugs produced large effect sizes (ie d>0.80; amphetamine, benzphetamine, fenfluramine and sibutramine). The placebo-subtracted weight losses for single drugs vs placebo included in the meta-analysis never exceeded 4.0 kg. No drug, or class of drugs, demonstrated clear superiority as an obesity medication. Effects of methodological factors are also presented along with suggestions for future research.

Rev Neurol. 2002 Apr 1-15;34(7):612-7.
The evolution of use of anti-Parkinson drugs in Spain
Montane E, Vallano Ferraz A, Castel JM.
Servicio de Farmacologia Clinica, Hospital Universitario Vall d'Hebron, Barcelona, Espana.

INTRODUCTION. In recent years new anti Parkinson drugs have been marketed and there has been controversy over the safety of some drugs. OBJECTIVE. To analyze the evolution of the consumption of anti Parkinson drugs and the effect of the newer drugs. PATIENTS AND METHODS. A study of the consumption of anti Parkinson drugs (1989 1998). Data were obtained from the ECOM database of the Ministry of Health and TEMPUS of the National Statistics Institute. The drugs were classified using the Anatomo Therapeutic Clinical Classification (ATC). Consumption was expressed in defined daily dosage (DDD) and the costs in euros. The drugs marketed since 1990 were classified as new drugs and the others as classical drugs. RESULTS. The total consumption of drugs increased from 1.92 DDD/1,000 inhabitants/day in 1989 to 3.64 DDD/1,000 inhabitants/day in 1998. The drugs showing the greatest increase were selegiline, pergolide and levodopa. The total pharmaceutical expenses tripled. There was a smaller increase in the consumption of new drugs (1.2% of the total in 1991 and 6.6% in 1998) than in their costs (6.7% of the total in 1991 and 38.8% in 1998). The cost per DDD of the new drugs increased five times (1989: 2.55 euros and 1998: 13.59 euros) and that of the classical drugs was similar (1989: 0.54 euros and 1998: 0.62 euros). CONCLUSIONS. The total consumption of anti Parkinson drugs has progressively increased. The consumption of selegiline has also increased in spite of controversy over its safety. The new drugs have a major economic effect.

Ann Pharm Fr. 1990;48(2):70-80.
Working hypothesis for the effect of GABAergic, glycinergic or glutamatergic drugs in the treatment of Parkinson disease
Vamvakides A.
Laboratoire Chropi, Paris.

The data obtained during the past decade in experimental and clinical pharmacology show that the GABAergic drugs, with central activity, do not ameliorate the symptoms of the Parkinson's disease (PD), but would worsen the akineto-rigid syndrome, the dyskinesias and the deteriorating mental status in the later stages of the PD. On the other hand, recent data of experimental pharmacology suggest the possibility that glycinergic or glutamatergic derivatives, with central activity, would have a beneficial effect on the syndromes of the later stages of PD (declining efficacy of L-DOPA, dyskinesias, deteriorating mental status), which constitute, with the fluctuation of the response to L-DOPA, ("on-off" effects), the major problems of the PD's treatment. Some theoretical and experimental data also suggest the possibility of a beneficial effect of the glutamatergic drugs in the treatment of the "on-off" effects.

Neurology 1985 Apr;35(4):571-3
Motor function in the normal aging population: treatment with levodopa
Newman RP, LeWitt PA, Jaffe M, Calne DB, Larsen TA
In normal elderly humans there is progressive motor dysfunction and loss of nigrostriatal neurons and brain dopamine similar to, although of a milder degree than, that seen in Parkinson's disease. Ten healthy elderly volunteers were given carbidopa/levodopa or placebo in a double-blind crossover study. We measured movement velocity, reaction time, tremor, visual evoked response (VER), and electroretinography (ERG). Significant changes were seen only in ERG. Motor functions and VER were unchanged. Although there appeared to be pharmacologic activity (ie, changes in ERG), levodopa, in adequate antiparkinson dosage, had no impact on the mild extrapyramidal impairment of normal elderly subjects.

 

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