Existing anti-obesity pills generally cut weight by five to 10 percent when taken for a year.

But men and women taking Excalia, the new pill developed by Californian biopharmaceutical firm Orexigen for 48 weeks lost 12 percent of their body weight, according to the online edition of Daily Mail.

A course of one a day of Excalia could have a dramatic effect on the quality of life and cut the risk of heart disease, diabetes and cancer, it said.

Many slimmers find that, after weeks of successfully losing weight, their metabolism slows down and they hit a plateau, the US scientists developing the pills say.

With the pounds slower to come off, many lose their resolve and end up piling weight back on.

Excalia gets round this by tricking the hypothalamus – the brain’s weight and appetite thermostat – into keeping the metabolism running fast.

The pill contains two drugs, which are already widely used, against epilepsy and smoking, so there is a reduced danger of side effects emerging in trials. The pills also boost levels of a hormone that stops us getting hungry, they said.

Ken Fujioka, one of the doctors running the trials, said: "The brain is good at figuring out that the body is losing weight. If a drug affects one pathway that could be used to bring the weight back, it will switch to another pathway. With a combination of drugs, we have a better chance of hitting two pathways and getting better and more sustained weight loss."

Obesity is increasingly recognized as a disorder of central nervous system regulation of appetite and energy expenditure. The brain, including the hypothalamus, plays a critical role in governing many fundamental processes throughout the body. The hypothalamus receives chemical and hormonal stimuli from various sources, including glucose, insulin, leptins and the peptides secreted by the gut as it processes food. These inputs govern a person’s appetite, satiety and energy expenditure. The brain governs body weight by establishing a setpoint, much like a thermostat in an air conditioning system. The body then tries to maintain this value even when the food supply varies a great deal. However, malfunctioning of this system may allow the setpoint to slide up or down, causing overeating and obesity on the one hand or progressive weight loss and cachexia, a physical wasting disorder, on the other.

The combinations Orexigen has chosen are based on the output of a low-throughput screening model developed by company co-founder and Chief Scientific Officer, Michael Cowley, Ph.D. This screening technology uses a mouse model that allows Orexigen’s solution to quantify firing rates for specific neuronal populations using green fluorescent protein tagging. In particular, research has shown that there is one group of hypothalamicneurons called proopiomelanocortin, or POMC, neurons that play a critical role in managing weight. By exposing POMC neurons in our mouse model to varying concentrations of one or more drug products, we are able to measure the difference in firing activity of these neurons at baseline and over time. This permits them to predict whether a drug will produce weight loss and, more importantly, whether the addition of a second drug has a previously undiscovered synergistic effect on POMC firing rates. Through studies they have screened several known compounds as part of the model’s validation. Their lead compounds, Contrave and Excalia, both demonstrated a strong synergistic profile with respect to POMC firing rates in the model. Additionally, they have verified this predicted synergy in more traditional animal feeding studies. Both combinations have subsequently demonstrated this synergy in human clinical trials.