In the field of pharmaceuticals, innovation can arise from unexpected origins. Take the Gila monster, a lethargic North American lizard with striking black and orange scales and a venomous bite. Despite spending most of its time underground and having infrequent eating habits, this creature has incidentally led to a breakthrough in modern medicine: the development of a new generation of weight-loss medications.
Discovering GLP-1: A Game-Changer in Diabetes Treatment
Back in the late 1980s, scientists discovered a gut hormone called GLP-1, which is released by the intestines after a meal. GLP-1 helps manage blood sugar by increasing insulin production (which lowers blood sugar) and reducing glucagon production (which raises blood sugar).
The challenge lay in the fact that natural GLP-1 breaks down rapidly in the body, so it couldn’t be used effectively as a drug. This meant that using it as a drug would require patients to get GLP-1 injections every hour, which was far from practical.
In 1990, John Eng, a researcher at the Veterans Affairs Medical Centre in The Bronx, made a remarkable discovery. He found a hormone called exendin-4 in the venom of the Gila monster, a venomous lizard. This hormone is similar to human GLP-1 but remains active in the body for a longer period.
This discovery was groundbreaking. It took over a decade of research and development. Eventually, a synthetic version of exendin-4, called exenatide, was developed by Eli Lilly, a major American pharmaceutical company, and Amylin Pharmaceuticals, a biotechnology firm.
Exenatide was approved in the United States for the treatment of diabetes. This success opened the door for other companies to develop even better and longer-lasting GLP-1 medications for diabetes treatment.
From Diabetes to Weight Loss
The GLP-1 drugs were initially developed to help manage diabetes. However, scientists soon discovered that these drugs also slowed the rate of stomach emptying, leading people to feel full for longer and reducing their appetite.
It wasn’t until 2021 that Novo Nordisk, a Danish pharmaceutical company, conducted a clinical trial of its GLP-1-based diabetes drug, semaglutide, marketed as Ozempic.
Over a period of 68 weeks, overweight or obese patients were given a weekly dose of semaglutide. The results were astonishing—participants lost an average of 15% of their body weight.
The Booming Market for GLP-1 Drugs
GLP-1 hormone-mimicking drugs have become major hits, with demand soaring as nearly 50% of the global population is expected to be obese or overweight by 2030.
Bloomberg estimates these drugs will reach $80 billion in yearly sales by 2030, with the market growing by 26% annually over the next five years. This growth outpaces that of oncology drugs (16% annually) and immunology medicines (4% annually).
Currently, three GLP-1 drugs are approved for obesity: liraglutide and semaglutide (Novo Nordisk) and tirzepatide (Eli Lilly). Nearly 100 new drugs are in development, aiming to be easier to take, cause fewer side effects, or be more effective.
Here is a table comparing the different companies and their GLP-1-related drug developments
| Company | Drug | Administration | Development Stage | Special Features |
|---|---|---|---|---|
| Novo Nordisk | Semaglutide (injection) | Weekly injection | Approved | Effective for weight loss and diabetes treatment. |
| Novo Nordisk | Semaglutide (oral) | Daily pill | In development (launch delayed) | Requires 20 times the amount of the active ingredient in the injection. |
| Eli Lilly | Tirzepatide | Weekly injection | Approved | Effective for weight loss and diabetes treatment. |
Innovations and Challenges
Researchers are working on making GLP-1 drugs more convenient and practical. Current issues include injection frequency, with weekly injections the norm, but companies are developing monthly options.
Additionally, Novo Nordisk is developing a daily pill formulation of semaglutide. Side effects such as nausea and vomiting are common, so Zealand Pharma is developing a drug based on a different hormone, amylin, to minimize these side effects.
Beyond Weight Loss: Multifaceted Health Benefits
GLP-1 drugs have a wide range of applications beyond weight loss. Obesity is associated with over 200 health issues, including strokes, kidney problems, and fatty liver. Recent studies by Novo have shown that semaglutide reduced serious heart problems by 20% in obese individuals even before weight loss.
In March 2024, semaglutide was approved to reduce the risk of heart disease in overweight individuals, marking the first time a weight-loss drug received this approval. Another drug, survodutide, is showing promise in treating a serious liver condition called metabolic dysfunction-associated steatohepatitis (MASH), caused by excessive fat accumulation in the liver.
Researchers have found that GLP-1 drugs also affect the brain and immune system by interacting with receptors in the brain. This could potentially aid in the treatment of brain disorders like Alzheimer’s and Parkinson’s disease.
Additionally, the appetite-suppressing effects of these drugs may be beneficial in curbing cravings, including those related to alcohol and other addictive substances.
While these discoveries are exciting, it’s essential to note that developing new drugs is a challenging and costly process, often accompanied by numerous failures along the way. Nevertheless, GLP-1 drugs have the potential to treat numerous conditions beyond obesity and diabetes, offering hope for many people’s health.
The journey of GLP-1 medications, from their origins in a lizard’s venom to their profound impact on modern medicine, is a testament to human ingenuity and persistence.
As research continues and innovations emerge, these drugs hold the promise of not only addressing obesity and diabetes but also providing new therapeutic options for a wide range of health conditions. With ongoing advancements and broader applications on the horizon, the future looks promising for these groundbreaking medications.
