Nadwaga i otyłość stanowią poważny problem medyczny i społeczny. W Europie i Stanach Zjednoczonych odsetek osób z BMI > 30 wynosi ponad 27% i stale wzrasta. Wiadomo także, że nadwaga jest istotnym czynnikiem ryzyka wielu chorób takich jak: nadciśnienie, choroba niedokrwienna serca, zaburzenia lipidowe, cukrzyca typu 2, choroby stawów, nowotwory i bezdech nocny. W niniejszej pracy zostaną przedstawione współczesne koncepcje dotyczące patogenezy nadwagi i otyłości ze szczególnym zwróceniem uwagi na rolę leptyny, receptorów (3 i serotoniny, a także związków o budowie peptydowej (CART, oreksyny, rezystyna, białako AGAP). W oparciu o najnowsze badania kliniczne omówiono leki najczęściej stosowane w leczeniu otyłości i nadwagi. Uwzględniając mechanizm działania leki podzielono na następujące grupy: 1) zmniejszające przyjmowanie pokarmów, 2) leki zmniejszające wchłanianie pokarmów, 3) leki zwiększające termogenezę. Szczególną uwagę zwrócono na ich działania niepożądane i skuteczność działania.

Obesity is the most common nutritional disorder in European and United States. Given a normal body-mass index (BMI) ranging approximately from 19 to 24.9, 34% of adult population is overweight and 27% is obese (BMI >30) in USA. Obesity is a critical risk factor for non-insulin dependent diabetes, cardiovascular disease i.e. hypertension, osteoarthritis, various forms of cancer and many physical problems such as sleep apnoea, joint and back pain. Many pharmacological agents are able to reduce food intake and decrease body mass when administered to animals. More limited clinical data demonstrates that some of the drugs produce decrease food intake and weight loss in human. Drugs approved for treatment of obesity fall into three broad groups:
a) appetite suppressant, i.e. drugs that reduce food intake by diminishing appetite or increase satiety,
b) drugs that reduce nutrient absorption, c) drugs that increase energy expenditure.
The noradrenergic agents such as phentermine, diethylpropion, phendimetrazine, mazindol, benzphetamine reduce food intake. These drugs are approved only for short-term use. Amphetamines are not longer used because of the risk for their abuse. Serotonergic drugs produce release of neuronal serotonin and inhibit its reuptake but fenfluramine and dexfenfluramine were withdrawn from the market in many countries (e.g. United States in 1947) because of serious side effects. Among mixed noradrenergic-serotonergic agents sibutamine is approved for long-term weight loss therapy.
Orlistat is the compound that reduces nutrient absorption due to binding to gastrointestinal lipases and subsequently, preventing hydrolysis of triglycerides into absorbable free fatty acids.
The termogenic drugs i.e. ephedrine and caffeine has not been longer approved by regulatory agencies in certain countries e.g. USA. ß3-adrenoreceptor agonists (CL316, LY-377604, ICID7114) have been reported to increase energy expenditure in human, but none have so far proved sustained efficacy in clinical trials. Drugs that can be considered suitable candidates for Ňappetite suppressantÓ are those that enhance peripheral peptide system (CCK, bombesin, GLP-1) or alter the CNS levels of various hypotalamic neuropeptides (e.g. NPY, galanin, CART, orexin, resistin, melanocortin).
Leptin, a hormone secreted by adipocites has become regarded as a key hormonal signal reflecting the lipid content of the total body of a nonfatting person. This hormone regulates functions through interactions with central and peripheral modulators such as NPY, melanocortins, CART, orexin and resistin. Interestingly, treatment of leptin-resistant obese children with recombinant human leptin induced a dramatic loss of body weight.