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Currently, obesity presents one of the biggest health problems. Management strategies for weight reduction in obese individuals include changes in life style such as exercise and diet, behavioral therapy, and pharmacological treatment, and in certain cases surgical intervention. Diet and exercise are best for both prevention and treatment, but both require much discipline and are difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it may only have modest results, limited by side effects; furthermore, the weight lowering effects last only as long as the drug is being taken and, unfortunately, as soon as the administration is stopped, the weight is regained. These strategies should be used in a combination for higher efficacy. Drugs used to induce weight loss have various effects: they increase satiety, reduce the absorption of nutrients or make metabolism faster; but their effect is usually moderate. In the past, several drugs were used in the pharmacological therapy of weight reduction including thyroid hormone, dinitrophenol, amphetamines and their analogues, e.g. fenfluramine, At present, only orlistat is available in the long term treatment (≥ 24 weeks) of obesity as sibutramine and rimonabant were withdrawn form the market. Several new anti-obesity drugs are being tested at present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most promising one.

The pharmaceutical search to induce weight loss was precipitated by the United States Food and Drug Administration's (FDA) 1959 formal approval of phentermine for short-term weight loss despite limited research supporting its assertions of weight loss. In addition to sympathomimetic amine products like phentermine, other medications considered in this article include herbal products, sibutramine, orlistat, metformin, and rimonabant. The use of pharmacotherapy for morbidly obese adolescents should be part of a comprehensive weight-loss program that recommends diet, exercise, and behavioral modification. Side effects and the possibility of major adverse effects should be remembered when considering use of these products., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The incidence of obesity and related co-morbidities such as insulin resistance, dyslipidemia and hypertension are increasing at an alarming rate worldwide. Current interventions seem ineffective to halt this progression. With the failure of leptin as an anti-obesity therapeutic, ciliary neurotrophic factor (CNTF) has proven efficacious in models of obesity and leptin resistance, where leptin proved ineffective. CNTF is a gp130 ligand that has been found to act centrally and peripherally to promote weight loss and insulin sensitivity in both human and rodent models. Future research into novel gp130 ligands may offer new candidates for obesity-related drug therapy.

Context: Obese individuals tend to resist the weight-regulating effects of exogenously administered leptin. A genetically engineered recombinant human variant ciliary neurotrophic factor (rhvCNTF) that signals through leptinlike pathways in the hypothalamus has been shown to bypass leptin resistance in animal models of obesity., Objective: To identify a safe and well-tolerated dose of rhvCNTF that causes weight loss in obese adults., Design, Setting, and Patients: Twelve-week, double-blind, randomized, parallel-group, dose-ranging, multicenter clinical trial conducted at 2 university obesity clinics and at 5 independent clinical research clinics from March 2000 to August 2001, and including 173 nondiabetic obese adults, 82.6% of whom were women, with a mean (SD) body mass index of 41.1 (4.1)., Interventions: Patients were randomly assigned to receive daily for 12 weeks subcutaneous injections of placebo (n = 32) or 0.3 microg/kg (n = 32), 1.0 microg/kg (n = 38), or 2.0 microg/kg (n = 33) of rhvCNTF. Another group received 1.0 microg/kg for 8 weeks and placebo for 4 weeks (n = 38), but they were not included in the primary analysis. All participants received instructions for a reduced-calorie diet (World Health Organization formula minus 500 kcal/d)., Main Outcome Measures: Change in weight during the 12-week double-blind treatment period and proportion of patients who achieved a weight loss of at least 5%., Results: Of the 173 randomized patients, 123 (71%) completed the double-blind dosing period. Mean (SEM) changes in kilograms from baseline body weights were 0.1 (0.6) for placebo and -1.5 (0.6) for the 0.3, -4.1 (0.6) for the 1.0, and -3.4 (0.7) for the 2.0 microg/kg of rhvCNTF dosage groups (P<.001, test for trend). Two patients (8.7%) in the placebo and 2 (8.3%) in the 0.3- microg/kg, 8 (29.6%) in the 1.0- microg/kg, and 5 (26%) in the 2.0- microg/kg treatment groups achieved a weight loss of at least 5%. Recombinant human variant CNTF was generally well tolerated although adverse events occurred in 75% of patients receiving placebo and 78% to 93% of patients receiving rhvCNTF, in a dose-related fashion, with mild injection site reactions as the most frequently reported adverse event., Conclusions: In this initial, dose-ranging, 12-week study, treatment with rhvCNTF resulted in more weight loss than placebo. These preliminary findings require confirmation in large prospective clinical trials.