Setmelanotide is a small protein drug. Small proteins are called peptides and names of peptides end in “-tide”. Setmelanotide acts like a hormone and stimulates the melanocortin 4 receptor (MC4R) in the brain and is a magic bullet for weight loss in certain kinds of extreme obesity.
It was discovered in 2008 that mutations in the gene that makes the MC4R and also mutations in the proteins that signal that receptor were associated with obesity. These MC4R mutations cause very severe obesity that starts at a very early age. It happens in 1.0–2.5% of people with obesity making it the most commonly known class of specific genetic defects causing obesity. But that’s still only a tiny minority of people with obesity and this drug is only aimed at a subset of these candidates. So don’t go out and buy stock just yet in Rhythm Pharmaceuticals, the company that is in the process of bringing setmelanotide to market by the end of 2020.
The results of early trials are impressive. In one kind of MC4R mutation obesity the subjects lost an average of 25% of their weight. That’s gastric bypass-like results. In another subtype of MC4R mutation, subjects lost a less impressive average 12.5% of their weight. But that’s still better than any other weight loss drug available today.
Even if this only helps a few people it teaches us some important things about obesity more generally. The first thing is that obesity is not about will power. Even though these rare birds are very hungry and eat a lot, hunger is very painful and not something you can reasonably put up with forever. The MC4 receptors in certain brain centers and the effects of setmelanotide also control the energy expenditure – calorie burning – of your body.
The MC4 receptor is at the crossroads of several other kinds of obesity and also mediates lots of other things not related to obesity or the energy economics of human bodies. So while this new weapon may cause some other unwanted side effects (so far so good), it or similar peptides may also be breakthrough therapy for lots of other forms of obesity and even type 2 diabetes. Then you should buy stock if it’s not too late because of insider trading.
John DiTraglia M.D. is a Pediatrician in Portsmouth. He can be reached by e-mail- firstname.lastname@example.org or phone (740) 354-6605.