A new anti-obesity drug – WegovyTM (semaglutide) – was approved by the FDA last month for the first time since 2014… but you will never guess where it came from!

Anti-obesity treatments have had a long and mixed history. The early Greek physician Hippocrates recognized the health risks of obesity and provided the classical recommendations of diet, exercise, and lifestyle alterations. Less successfully, he also recommended the use of emetics and cathartics, which are drug molecules that induce vomiting and defecation, respectively. While these have been the conventional obesity treatments for thousands of years, the soaring rate of obesity during the 20th century led to the need for new treatments, which ranged anywhere from jaw wiring, bariatric surgery (e.g. lap band or gastric bypass operations), diet pills such as fenfluramine/phentermine (fen-phen) – which were ultimately recalled due to their link with heart valve damage – and vagotomy operations.

A vagotomy is a surgical procedure that involves removing or snipping part of the vagus nerve, which connects the gut and the brain. It is the conduit through which messages about digestion are sent to your brain, such as how full you are based on how stretched your stomach is. It also sends messages to different regions of the brain, mediating appetite, fat storage and energy levels. Dysfunction of this source of communication has been implicated with metabolic disorders such as obesity and diabetes, with the vagotomy procedure seeming to recalibrate dysfunctional signalling. Unfortunately, vagotomies have now been abandoned, as follow-up studies showed that the regeneration of the vagus nerve that occurs in the months and years after surgery leads to weight regain.

3d rendered medically accurate illustration of a female brain anatomy
A new anti-obesity drug called semaglutide targets areas of the brain that regulate appetite and food intake.

While vagotomy procedures weren’t themselves successful, the idea behind them was a key precursor to a newly-approved anti-obesity drug. This drug – with the scientific name semaglutide or the brand name WegovyTM – sends messages to the brain via the vagus nerve. Instead of snipping this nerve to stop dysfunctional signalling in the case of a vagotomy, this new drug  activates the vagus nerve system of morbidly obese patients to reduce their appetite and food intake, recalibrating their perception and desire for sweetness and food intake, and ultimately reducing their weight. Semaglutide has also been shown to help bring blood glucose levels to a healthy range. 

Even though clinical trials involving semaglutide outperformed alternative anti-obesity drugs to help people lose ~ 15% of their body weight on average over a 68-week period, it is where the drug came from that is truly remarkable.

The Gila monster (Heloderma suspectum) is one of two poisonous lizards in the United States. It ranges in parts of California, Arizona, Nevada, Utah, New Mexico, and northwest Mexico. It’s also where semaglutide comes from!

Semaglutide was isolated from the venom of a reptile known as the Gila monster (Heloderma suspectum). While a typical bite from the Gila monster can cause extreme pain and discomfort that can last for hours, the isolation of semaglutide from the toxic venom cocktail and administration to patients can reduce the pain, discomfort, and health consequences associated with obesity and type 2 diabetes. The origin of this discovery began in 1995 when Canadian endocrinologist Dr. Daniel J. Drucker had this lizard shipped to his laboratory, after learning that its venom contained hormones that could regulate blood sugar. Ten years later, a synthetic version of a molecule in the lizard’s venom was developed to treat type 2 diabetes, and has now been approved by the FDA to treat chronic obesity or overweight.

The FDA highlights potential side effects of semaglutide that include nausea, diarrhea, vomiting, headache, and fatigue, and highlights that patients should discuss with their healthcare professional if they have symptoms of pancreatitis or gallstones (among other conditions) before starting treatment. 

Despite these side effects, the discovery of the venom-derived semaglutide drug opens a new chapter for obesity treatment, one that many people would agree is definitely preferable to jaw wiring or heart-damaging diet pills!