Obesity Drugs: The discovery of the GLP-1 hormone changed everything in the way we treat obesity and diabetes. The landmark studies about the hormone created blockbuster drugs Wegovy and Ozempic, which changed millions of lives over night. Inducted into the prestigious Lasker Awards, and the scientists who have been part of this work—Dr. Joel Habener, Dr. Svetlana Mojsov, and Dr. Lotte Bjerre Knudsen—stand on pillar foundations of history in medical research. Let us look into the importance of the GLP-1 hormone in obesity treatment and how these researchers paved their way into creating these drugs.
The Lasker Awards
Among the most elitist of awards in medicine, Lasker Awards are often considered precursors to the Nobel Prize, providing lofty honors for work in medicine and public health, which eventually makes a marked difference to society. In recognition of innovative work on the GLP-1 hormone, this year’s Lasker-DeBakey Clinical Medical Research Award goes to Dr. Joel Habener, Dr. Svetlana Mojsov, and Dr. Lotte Bjerre Knudsen, whose efforts paved the way for new treatments for obesity and diabetes.
The Journey to GLP-1 Discovery
The story of research into the GLP-1 hormone started back in the 1970s when Joel Habener, an endocrinologist at Massachusetts General Hospital, initiated the search. Having habituated to glucagon, a releasing hormone, he had a certain interest in glucagon’s role in blood sugar regulation; it was there that while working on anglerfish, he found a gene that resembled the gene for glucagon, but this soon proved to be the actual discovery for GLP-1.
A turning point in the study of GLP-1 came when Graeme Bell of the Chiron Corporation identified a similar protein in hamsters in 1983. This protein, glucagon-like peptide-1 (GLP-1), would soon become the center of much scientific study.
Dr. Svetlana Mojsov’s Breakthrough: The Active Form of GLP-1
Enter Dr. Svetlana Mojsov, a young researcher working at Massachusetts General Hospital who proved important to the identification of the biologically active form of GLP-1. Dr. Mojsov reasoned that just because the body produces GLP-1, it must first act to remove the first six amino acids, forming the active version. She proved this with advanced chemical methodologies and then synthesized the shorter, active version of GLP-1.
Dr. Mojsov demonstrated that GLP-1 is secreted in the intestine. Acting on the insulin-producing cells of the pancreas, it modulates blood sugar levels with the precision of a Swiss watch. Thus, through her work, use of GLP-1 was possible for both diabetes treatment and obesity.
The Role of Lotte Bjerre Knudsen: Extending GLP-1’s Impact
But one of the biggest challenges was that the hormone had a half-life of just about three minutes in the body. That is where Lotte Bjerre Knudsen, a researcher at Novo Nordisk, came in. Inspired by the works of Dr. Stephen Bloom, Knudsen had an epiphany that GLP-1 could also affect weight loss along with regulating blood sugar levels.
It was through this breakthrough that Knudsen succeeded in ascertaining that she could prolong the survival of the hormone if she attached a fatty acid that is bound to albumin, a blood protein. Her innovation would result in developing liraglutide, a drug that is based on GLP-1 with a duration of action as long as 13 hours in the body. Liraglutide was marketed as Saxenda, and it is the first approved GLP-1 drug that is used for obesity treatment, dated 2014.
The Emergence of Blockbuster Drugs: Wegovy and Ozempic
But just to create liraglutide was merely the first step; Novo Nordisk researchers upgraded GLP-1 analogues until they prepared semaglutide, a molecule that can stay in the body for up to a week. Semaglutide is the active ingredient in two blockbusters: Ozempic, for the treatment of type 2 diabetes, and Wegovy, for obesity therapy.
These drugs are a giant leap forward in the treatment of obesity, achieving a weight loss per patient of 15% on average—a feat considered impossible not long ago for the scientific fields. According to Indiana University’s chemistry professor, Dr. Richard DiMarchi, “it broke the’sound barrier’ of weight loss where earlier interventions had only been able to reach about 10%.
The Future of GLP-1 Research
The future of obesity treatment has been found to be promising with the success of drugs based on GLP-1. Researchers are now looking into how the analog of GLP-1 can be optimized further to develop even more effective treatments with less side effects. As science goes, we can expect a growing number of competitors in the obesity drug market as pharmaceutical companies look for alternatives for Wegovy and Ozempic.
Obesity Drugs: How It Work
The GLP-1 hormone, or Glucagon-Like Peptide-1, is of great importance in glucose metabolism and appetite regulation. Its action starts with secretion from the intestines following ingestion and stimulates the pancreas to emit additional insulin. Blood sugar levels are kept ideal since secretion of glucagon—a hormone that increases blood sugar—is suppressed.
The other pathway of action of GLP-1 is its effect on the central nervous system, and more specifically on the hypothalamus of the brain that regulates hunger. Injection of GLP-1 activates some receptors in the brain to suppress appetite and food consumption, both of which would contribute to weight loss. However, the endogenous form of GLP-1 is not stable and has a very short half-life, less than a few minutes, so it is not suitable for direct use as a drug.
To combat this, scientists created GLP-1 analogs—synthetic versions of the hormone that are designed to stay in circulation for longer periods of time. Such analogs, including liraglutide and semaglutide, have a much slower rate of degradation compared with the natural hormone because they stick to these GLP-1 receptors but are resistant to degradation occurring at the same site. These extended periods of activity mean they can provide more sustained control over both blood glucose as well as appetite suppression, such that GLP-1 analogs have been proven to be particularly effective treatments for type 2 diabetes and obesity.
FAQs
- What is GLP-1?
- GLP-1 is a hormone that regulates blood sugar levels and has been found to aid in weight loss.
- What drugs are based on GLP-1?
- Drugs like Ozempic and Wegovy are based on GLP-1 analogs and are used to treat type 2 diabetes and obesity.
- How does GLP-1 help with weight loss?
- GLP-1 affects appetite regulation in the brain, reducing food intake and promoting weight loss.
- What is the significance of the Lasker Awards?
- The Lasker Awards honor major contributions to medicine and public health, often predicting future Nobel Prize winners.
- Who are the scientists behind the GLP-1 discovery?
- Key contributors include Dr. Joel Habener, Dr. Svetlana Mojsov, and Dr. Lotte Bjerre Knudsen.
- What is the difference between Ozempic and Wegovy?
- Both drugs are based on semaglutide, but Ozempic is primarily used for diabetes, while Wegovy is for obesity.
- How long do GLP-1 drugs last in the body?
- Modern GLP-1 drugs like semaglutide can last up to a week in the body.
- What was the first GLP-1 drug approved for obesity?
- Liraglutide (marketed as Saxenda) was the first GLP-1 drug approved for obesity treatment.
- Can GLP-1 drugs prevent diabetes?
- GLP-1 drugs can help manage blood sugar and may prevent type 2 diabetes in individuals with obesity.
- Are there any side effects of GLP-1 drugs?
- Common side effects include nausea, vomiting, and diarrhea, but these usually subside after the body adjusts to the medication.
The discovery and development of GLP-1 analogs have revolutionized the treatment of obesity and type 2 diabetes. The work of Dr. Joel Habener, Dr. Svetlana Mojsov, and Dr. Lotte Bjerre Knudsen, recognized by the Lasker Awards, has paved the way for effective and life-changing treatments. As research continues to evolve, the future of obesity treatment looks bright, with new innovations on the horizon.
