Next generation of weight management medications: implications for diabetes and CVD risk.

Since the 1980s, the prevalence of obesity has almost doubled worldwide. Treatments for obesity include lifestyle modification, medications and surgery. Newer anti-obesity medications have been shown to be effective at inducing initial weight management in addition to successful long-term weight maintenance. Historically, weight management medications have been associated with public safety concerns that have resulted in the majority being withdrawn from the market or never receiving medicinal authorization. Recently, several countries have approved some newer generation weight management medications which may be beneficial to combat obesity. These medications have varying effects on cardiometabolic parameters, both positive and potentially negative. This review will outline the mechanisms of action of these medications and their implications for both diabetes and cardiovascular risks.

A study of the use of drugs in the treatment of obesity among adult females.

PURPOSE: Obesity is a prevalent health problem among adult females in Egypt. The aim of this study is to investigate the use of drugs in managing of obesity among adult females. DESIGN/METHODOLOGY/APPROACH: A random sample of 764 obese adult females with a BMI >25 were included in the study. Data were collected using a pre-coded questionnaire on personal characteristics, type of regimen followed, the use of anti-obesity drugs, sources of information about medicine, compliance pattern and the outcome of using medicine. FINDINGS: The results show that 19.9 per cent of the females took medicines while dieting and another 11.4 per cent while dieting and exercising. Physicians were the main source of advice about anti-obesity medicine (33.1 per cent), followed by pharmacists (25.5 per cent), peers (24.2 per cent) and mass media (17.2 per cent). Medicines stimulating the metabolism were most commonly used (42.7 per cent), followed by drugs blocking fat absorption (24.3 per cent), appetite depressants (23.3 per cent) and herbs (18.4 per cent). The most common side effects were diarrhoea (30.1 per cent) followed by headache (20.1 per cent) and depression (17.2 per cent). The data show that 47.7 per cent of the females fully complied while 30.5 per cent did not comply. The intake of medicine while dieting induced weight loss among 48.9 per cent of the subjects, 18.0 per cent did not report weight loss and 33.1 per cent stopped medicine intake. Older females and those with a BMI >35 were more keen to seek advice from a physician, were more likely to comply fully and reported the highest rate of weight loss. The use of anti-obesity drugs was highest (44 per cent) among university graduates compared to 24.8 per cent among females with limited education. ORIGINALITY/VALUE: This study presents the first report of the pattern of using anti-obesity drugs in Egypt.

[The harmfulness of drugs and slimming substances--a toxicologist's point of view]. / Szkodliwosc leków i srodków wspomagajacych odchudzanie--punkt widzenia toksykologa.

Obesity in rapidly developing countries has recently become an epidemic. That is why the need to fight against this chronic disease is becoming more and more apparent. In order to lose weight it is necessary to achieve negative energy balance either by increasing physical activity or using a low calorie diet. When these methods are ineffective, pharmacotherapy is used. The criterion for the application of medical treatment is a BMI above 30 kg/m2 or above 27 along with the presence of other risk factors. Drugs for weight loss fall into three groups: appetite inhibitors, those increasing energy expenditure by enhancing thermogenesis and those inhibiting the absorption of food in the intestines. This paper presents an overview of these classes of drugs and dietary supplements with an emphasis on their adverse effects and the possibility of poisoning. Despite the fact that in Poland only one drug - orlistat has been registered for the treatment of obesity, the availability of other products is unlimited due to the Internet. This fact, and the tendency of patients to treat obesity by themselves using pharmacological substances, poses a major threat and a challenge to the toxicologist.

Pharmacological therapies to address obesity in type 1 diabetes.

PURPOSE OF REVIEW: Obesity is increasing in prevalence among patients with type 1 diabetes (T1D) and is associated with insulin resistance and increased cardiovascular risk. The management of obesity in this population is complicated by defects in pancreatic islet hormone secretion and the effects of exogenous insulin treatment. Here, we review the effects of antiobesity medications and adjunct-to-insulin medications on body weight in T1D. RECENT FINDINGS: There is a profound evidence gap around the use of drugs for the treatment of obesity in T1D since systematic studies have not been performed in this population. Adjunctive-to-insulin therapy with certain antihyperglycemic agents leads to modest weight loss and reductions in insulin dose in T1D. However, only pramlintide has been approved in the United States for clinical use as adjunctive therapy in T1D. SUMMARY: The growing prevalence of obesity in T1D has created an unmet need for safe and effective therapies to treat overweight and obesity in this population. Currently, antiobesity medications are used off-label for the treatment of patients with T1D. Additional studies are needed to understand the role of these medications in the management of obesity in patients with T1D.

Strategies and potential molecular targets for obesity treatment.

Obesity is an increasingly prevalent and important health problem. Although treatment is available, the long-term maintenance of medically significant weight loss (5 to 10 percent of initial body weight) is rare. Since 1995 there has been an explosion of research focused on the regulation of energy balance and fat mass. Characterization of obesity-associated gene products has revealed new biochemical pathways and molecular targets for pharmacological intervention that will likely lead to new treatments. Ideally, these treatments will be viewed as adjuncts to behavioral and lifestyle changes aimed at maintenance of weight loss and improved health.

Are peptide conjugates the golden therapy against obesity?

Obesity is a worldwide pandemic, which can be fatal for the most extremely affected individuals. Lifestyle interventions such as diet and exercise are largely ineffective and current anti-obesity medications offer little in the way of significant or sustained weight loss. Bariatric surgery is effective, but largely restricted to only a small subset of extremely obese patients. While the hormonal factors mediating sustained weight loss and remission of diabetes by bariatric surgery remain elusive, a new class of polypharmacological drugs shows potential to shrink the gap in efficacy between a surgery and pharmacology. In essence, this new class of drugs combines the beneficial effects of several independent hormones into a single entity, thereby combining their metabolic efficacy to improve systems metabolism. Such unimolecular drugs include single molecules with agonism at the receptors for glucagon, glucagon-like peptide 1 and the glucose-dependent insulinotropic polypeptide. In preclinical studies, these specially tailored multiagonists outperform both their mono-agonist components and current best in class anti-obesity medications. While clinical trials and vigorous safety analyses are ongoing, these drugs are poised to have a transformative effect in anti-obesity therapy and might hopefully lead the way to a new era in weight-loss pharmacology.

Classification of Therapeutic and Experimental Drugs for Brown Adipose Tissue Activation: Potential Treatment Strategies for Diabetes and Obesity.

OBJECTIVE: Increasing efforts are being made towards pharmacologic activation of brown adipose tissue (BAT) in animals and humans for potential use in the treatment of obesity and diabetes. We and others have reported a number of animal studies using either experimental or therapeutic drugs. There are now efforts to translate these findings to human studies. The goal of this review is to evaluate the various drugs currently being used that have the potential for BAT activation. METHODS: Drugs were classified into 4 classes based on their mechanism of action. Class 1 drugs include the use of ß3 adrenoceptor agonists for BAT activation. Class 2 drugs include drugs that affect norepinephrine levels and activate BAT with the potential of reducing obesity. Class 3 includes activators of peroxisome proliferator-activated receptor-γ in pursuit of lowering blood sugar, weight loss and diabetes and finally Class 4 includes natural products and other emerging drugs with limited information on BAT activation and their effects on diabetes and weight loss. RESULTS: Class 1 drugs are high BAT activators followed by Class 2 and 3. Some of these drugs have now been extended to diabetes and obesity animal models and human BAT studies. Drugs in Class 3 are used clinically for Type 2 diabetes, but the extent of BAT involvement is unclear. CONCLUSION: Further studies on the efficacy of these drugs in diabetes and measuring their effects on BAT activation using noninvasive imaging will help in establishing a clinical role of BAT.

Pharmacotherapy for obesity.

Pharmacotherapy for the management of obesity is primarily aimed at weight loss, weight loss maintenance and risk reduction, and has included thyroid hormone, amphetamines, phentermine, amfepramone (diethylpropion), phenylpropanolamine, mazindol, fenfluramines and, more recently, sibutramine and orlistat. These agents decrease appetite, reduce absorption of fat or increase energy expenditure. Primary endpoints used to evaluate anti-obesity drugs most frequently include mean weight loss, percentage weight loss and proportion of patients losing >or=5% and >or=10% of initial bodyweight. Secondary endpoints may include reduction in body fat, risk factors for cardiovascular disease and the incidences of diseases such as diabetes mellitus. Most pharmacotherapies have demonstrated significantly greater weight loss in patients on active treatment than those receiving placebo in short-term (or=10% loss of initial bodyweight in 46% of patients. For patients taking orlistat, weight loss was 2.2 kg greater than those on placebo at 4 years (p<0.001), with significantly more patients achieving >or=10% loss of initial bodyweight (26.2% and 15.6%, respectively; p<0.001). Other drugs that have been evaluated for weight loss include ephedrine, the antidepressants fluoxetine and bupropion, and the antiepileptics topiramate and zonisamide. Two clinical trials with fluoxetine both reported no significant difference in weight loss compared with placebo at 52 weeks. Clinical trials evaluating ephedrine, bupropion, topiramate and zonisamide have demonstrated significantly greater weight loss than placebo but have been limited to 16-26 weeks' treatment. A major obstacle to the evaluation of the clinical trials is the potential bias resulting from low study completion rates. Completion rates varied from 52.8% of phentermine recipients in a 9-month study, to 40% of fenfluramine recipients in a 24-week comparative study with phentermine and 18% of amfepramone recipients in a 24-week study. One-year completion rates range from 51% to 73% for sibutramine and from 66% to 85% for orlistat. Other potential sources of bias include run-in periods and subsequent patient selection based on compliance or initial weight loss. Several potential new therapies targeting weight loss and obesity through the CNS pathways or peripheral adiposity signals are in early phase clinical trials. Over the next decade the drug treatment of obesity is likely to change significantly because of the availability of new pharmacotherapies to regulate eating behaviours, nutrient partitioning and/or energy expenditure.

A perspective on the current strategies for the treatment of obesity.

The prevalence in obesity has increased dramatically over the past 30 years, more than double in the United States alone. Obesity is associated with an increased risk for type 2 diabetes mellitus, dyslipidemia, hypertension, biliary disease, obstructive sleep apnea, and certain types of cancer. The pathophysiology of obesity is complex, involving behavioral, environmental, and genetic factors. Current treatment options include behavior modification and lifestyle changes which incorporate weight-reducing diets and physical activity, FDA approved long-term anti-obesity pharmacological agents sibutramine and orlistat, non-FDA approved over-the-counter (OTC) supplements and nutriceuticals, and, when appropriate, bariatric surgery. Without adequate prevention and treatment of obesity, government agencies have suggested that the direct and indirect costs associated with obesity may overwhelm the healthcare system. This brief review explores the current data available on treatments for the obese patient including the relative merits of different types of macronutrient composition (e.g., low carbohydrate vs. high carbohydrate diets) of weight-reducing diets, the value of resistance/ strength training in physical activity programs designed for the obese patient, the safety and efficacy associated with OTC supplements and nutriceuticals for weight reduction (e.g., Ephedra, conjugated linoleic acid (CLA), Garcinia cambogia/ hydroxycitric acid (HCA), chromium, pyruvate), the safety and efficacy of FDA-approved long-term obesity treatments sibutramine and orlistat, and bariatric surgery.

Gut hormones as peripheral anti obesity targets.

Many peptides are synthesised and released from the gastrointestinal tract. Whilst their roles in regulation of gastrointestinal function have been known for some time, it is now evident that they also influence eating behaviour and thus potential anti obesity targets. Peptide YY (PYY) is released post prandially from the gastrointestinal L-cells with glucagon-like peptide 1 (GLP-1) and oxyntomodulin. Following peripheral administration of PYY 3-36, the circulating form of PYY, to mouse, rat or human there is marked inhibition of food intake. PYY 3-36 is thought to mediate its actions through the NPY Y2 GPCR. Obese subjects have lower basal fasting PYY levels and have a smaller post prandial rise. However, obesity does not appear to be associated with resistance to PYY (as it is with leptin) and exogenous infusion of PYY 3-36 results in a reduction in food intake by 30% in an obese group and 31% in a lean group. GLP-1 or oxyntomodulin, products of the prepreglucagon gene, decrease food intake when administered either peripherally or directly into the CNS. In addition, both have been shown to decrease food intake in humans. These effects are thought to be mediated by the GLP-1 receptor. Ghrelin, a huger hormone produced by the stomach, increases in the circulation following a period of fasting. Administration of ghrelin either peripherally or directly into the CNS increases food intake and chronic administration leads to obesity. Further infusion into normal healthy volunteers increases both food intake and appetite. Ghrelin is thought to act through the growth hormone secretagogue receptor (GHS-R). Obesity is the current major cause of premature death in the UK, killing almost 1000 people a week. Worldwide its prevalence is accelerating. The administration of the naturally occurring gut hormone may offer a long-term therapeutic approach to weight control. Here we consider the therapeutic potential of some gut hormones, and the GPCR's through which they act, in the treatment of obesity.

[Pharmacological treatment of obesity]. / Tratamiento farmacológico de la obesidad.

The pharmacological treatment of obesity should be considered when cannot be achieved a 10% weight loss with diet therapy and physical activity. The drugs effective in obesity treatment may act by different mechanisms such as reduction in food intake, inhibition of fat absorption, increase of thermogenesis and stimulation of adipocyte apoptosis. At present, we only have two marketed drugs for obesity treatment. Sibutramine is an inhibitor of norepinephrine, dopamine and serotonina reuptake which inhibits food intake and increases thermogenesis. Sibutramine administration for a year can induce a weight loss of 4-7%. Its main side effects are hypertension, headache, insomnia and constipation. Orlistat is an inhibitor of pancreatic lipase which is able to block the absorption of 30% of ingested fat. Its administration induces weight loss and reduction of ulterior weight regain. Also, this drug improves hypertension dyslipdaemia and helps to prevent diabetes in 52% of cases when administered over four years. The increase in frequency of stools and interference with vitamin absorption are its main side effects. Glucagon-like peptide 1, which increases insulin sensitivity and satiety, adiponectin and PPAR-gamma agonists which reduce insulin resistance and modulates adipocyte generation are the basis for future therapeutic approaches of obesity. Phosphatase inhibitors induce PPAR-gamma phosphorylation and UCP-1 expression leading to an increase in thermogenesis and reduction in appetite.

[Statement about the medical and surgical treatment of overweight and obesity]. / Tratamiento farmacológico o quirúrgico del paciente con sobrepeso u obesidad.

This is an updated review of the available treatments for obesity, which can be used when lifestyles modifications fail. Using the available information and the experience of the members of this advisory group, a recommendation is given about the most useful treatments, according to the severity of obesity and its complications. With regards to pharmacological treatments, only sibutramine and orlistat are approved on a worldwide basis for the treatment of obesity. These medications achieve a 10% higher weight reduction than lifestyles modification. A third medication, rimonobant, is also more effective than lifestyles modifications, but it was withdrawn due to psychological safety issues. The indications for surgical treatment and a brief description of the available techniques, success rates and complications are outlined. Finally, the need to have followed up protocols for patients and the formation of multidisciplinary treatment teams is underscored.

Tratamiento farmacológico o quirúrgico del paciente con sobrepeso u obesidad / Statement about the medical and surgical treatment of overweight and obesity

This is an updated review of the available treatments for obesity, which can be used when lifestyles modifications fail. Using the available information and the experience of the members of this advisory group, a recommendation is given about the most useful treatments, according to the severity of obesity and its complications. With regards to pharmacological treatments, only sibutramine and orlistat are approved on a worldwide basis for the treatment of obesity. These medications achieve a 10 percent higher weight reduction than lifestyles modification. A third medication, rimonobant, is also more effective than lifestyles modifications, but it was withdrawn due to psychological safety issues. The indications for surgical treatment and a brief description of the available techniques, success rates and complications are outlined. Finally, the need to have followed up protocols for patients and the formation of multidisciplinary treatment teams is underscored.

Antiobesity drugs: current and future issues.

Overweight and obesity affect more than 60% of the population in the United States. Many social and environmental factors influence this phenomenon. Because of the tremendous difficulties associated with addressing these factors, health care providers have been looking for a magic pill that resolves this tissue. Although there is no panacea, this article is intended to concisely review commonly prescribed medications for obesity, their efficacy, and side effects. In addition, some pharmacologic agents with a promising antiobesity action are discussed.

The influence of obesity on the frequency and distribution of medication.

Obesity is a serious health problem in industrialized countries and is associated with a significant increase in total health care costs. Only few data are available about the costs of drug therapies in patients with an increased body weight treated under clinical routine procedures. Such data could support efforts to intensify obesity prevention and treatment programmes in order to reduce comorbidities and costs. We have evaluated body mass index (BMI), diagnosis, and medication in 3360 outpatients (2175 women and 1185 men; mean age: 56.7 +/- 17.5 years). All patients underwent physical examinations, including BMI determination, and provided a detailed record concerning medication. In 1809 patients, the percentage of body fat content was measured with a bioimpedance method (OMRON BF 302 body fat monitor). Continuous variables were compared using the t-test or Wilcoxon U-test. Frequency distributions were compared using chi-squared tests. With respect to BMI, most of the patients (n = 1793; 53 %) were overweight or obese, 1349 (40 %) showed a normal BMI and 218 (7 %) a low BMI. The majority of cardiovascular (61 %), rheumatological (61.1 %) and metabolic (60.4 %) medication was administered to overweight and obese patients. Parallel findings could be obtained by analysing the percentage of body fat and the frequency of medication. Overall, 82.5 % of all medication was given to patients with a body fat content >20 %. Our results support the importance of weight-reduction programmes in order to prevent an overall increase in the costs of medication as a consequence of overweight and obesity.

[Novel anti-obesity drugs]. / Neue Antiadiposita.

Obesity is a chronic disease with a worldwide increasing incidence. The mainstay of therapy consists in modification of behaviour related to obesity such as overeating and physical inactivity. When these life-style modifying attempts fail, the use of anti-obesity drugs is warranted. Public health efforts and current anti-obesity agents have not controlled the increasing epidemic of obesity, which has led to an extensive research on novel anti-obesity agents. This review presents an overview on potential future candidates.

Sibutramina / Sibutramine

Sibutramine is a drug that recently been accepted for its use in obesity: Here we shall review its actions and its role in the pharmacologic therapy of obesity, its indications and interactions. We shall also see the associations sibutamine has with the patologies most frecuently associated with obesity