In essence, the reasons that anti-obesity drugs have been so unsuccessful is that any drug that has been found to work reducing obesity has had a negative safety profile. The systems that control body weight and metabolism are very complex and overlap, so influencing one influences another. The receptors that trigger the effects that drug developers want are the same that the body uses for a variety of vital bodily processes, so specific targeting has been impossible.
There are some drugs in development targeting metabolic tissues but none has reached clinical development. The regulatory requirements for anti-obesity drugs are very stringent and it is unclear whether any of these drugs will meet the required levels of efficacy and safety.
Here is the full scientific article if you wish to download it.
Developments in the understanding of the webs of peptide interactions in metabolism have led to some promising developments. One pathway, the GLP-1, has already shown success with diabetes and could be used to treat obesity.
The reasons that anti-obesity drugs have been failures in the past are complex and frustrating. The human body is extremely complex and the causes of obesity are tied up in lots of different vital processes. By targeting one receptor, a drug inadvertently targets another or several different metabolic processes.
The patient might lose weight but the effects can be as varied as heart disease and psychosis. Drawbacks like these have frustrated research into obesity treatments for decades.
The drugs currently being investigated and evaluated for their use in treating obesity face similar hurdles. While the understanding of the complex layers of reactions and interactions in the hormone systems that govern body weight is improving, it is still full of holes and is not thought to be anywhere near complete.
Without this fundamental knowledge, it is difficult to know whether a drug in development can and will succeed. Peptide signaling is much better understood than it was even 10 years ago but the more that is understood, the more researchers realize how limited this avenue is.
One area of interest is the endocannabinoid system. The effects of phytocannabinoids on food intake have been known for years but now the mechanisms by which they mediate this effect are being uncovered. The general tolerability of cannabinoids is thought to be of special appeal, especially when compared to hormone treatment.
The mechanisms of human metabolism are finally being discovered. This has taken a long time and has relied upon a lot of hard work and increasingly sophisticated technology. Now the maps of interactions within the body are more known, future anti-obesity drugs can be developed that will exploit these interactions and hopefully help people lose weight in a safe way.
The complexity and interconnectedness of the metabolic signaling processes in the body have for a long time frustrated scientists seeking anti-obesity drugs. Now that they are more understood, the process of discovering and evaluating potential drugs for treating obesity will be easier. However, many of the drugs currently in development are likely to fail and it will be some time before effective and safe drugs are developed.