Lasker Award and GLP-1

Accessible Rail Medical Services Tetsuikai, Navitas Clinic Kawasaki, Tetsuya Tanimoto, MD

GLP-1 receptor agonists are very popular around me. Not only do I often prescribe them to my patients, but an increasing number of healthcare professionals and staff around me have also started using them. There are rumors that some medical practitioners are like Roman aristocrats who use expensive drugs while enjoying gourmet meals. I myself have been fasting for more than 3 years without any medication, but most people seem to use GLP-1 receptor agonists for weight loss.

On September 20, the Lasker–DeBakey Clinical Medical Research Award was presented for the development of a GLP-1 receptor agonist for the treatment of obesity. Established in 1945 by Albert Lasker, an American businessman who made his fortune in the advertising business, and his wife, Mary, a philanthropist, the award consists of four categories for medical research and public health activities. It is also known as the U.S. version of the Nobel Prize, and in fact, about a quarter of the 400-odd Nobel Prize winners to date have received the award.

This year's Lasker–DeBakey Clinical Medical Research Award was awarded to Joel Habener, Svetlana Moisov, and Lotte Bierre Knudsen. It is still fresh in our minds that Karikó Katalin and Drew Weissman, who won the same prize for 21 years, were awarded the Nobel Prize in Physiology or Medicine last year. Among Japanese, Shinya Yamanaka, Susumu Tonegawa, and Yoshinori Okuma were awarded both the Lasker award and Nobel Prize.

Habener, an endocrinologist at Massachusetts General Hospital in Boston, led the research that led to the discovery of the GLP-1 hormone in the 1980s, focusing on a hormone associated with the development of type 2 diabetes, and after cloning the glucagon gene, which raises blood sugar levels, he also discovered that this gene encodes another hormone He discovered that it encoded another hormone, later named GLP-1, a related hormone that stimulates the pancreas to produce insulin. Instead of insulin injections for diabetics, GLP-1 administration paved the way to theoretically encourage the body to produce insulin on its own.

Around the same time, biochemist Moisov of Massachusetts General Hospital identified the amino acid sequence of biologically active GLP-1 and demonstrated that this active GLP-1 stimulates insulin secretion from the pancreas in rats. This was an important step toward practical application.

After these initial discoveries, a serious barrier to clinical application was the fact that GLP-1 is metabolized very quickly and only lasts a few minutes in the blood. Here, Novo Nordisk scientist Knudsen played an important role. Since regular GLP-1 does not work as a drug, he devised a way to bind a fatty acid to GLP-1. This modification allowed the molecule to maintain its activity in the body for a longer time, enabling its effects to be exerted before degradation.

The results of this research led to the long-acting GLP-1, “liraglutide,” which was approved by the U.S. Food and Drug Administration for diabetes treatment in 2010. Its impact on weight loss also drew attention, and in 2014, the indication for obesity treatment was added. Subsequently, new drugs with similar mechanisms, such as “semaglutide” and “tirzepatide,” have been developed, achieving an average weight loss of over 15-20%, which has gained global recognition.

GLP-1 receptor agonists not only treat obesity and diabetes but also demonstrate effects on cardiovascular diseases, sleep apnea, kidney diseases, and reductions in overall mortality through actions on the brain and anti-inflammatory effects. Research is also progressing on their applications in metabolic liver disease, peripheral artery disease, Parkinson’s disease, Alzheimer’s disease, and various neuropsychiatric disorders and addiction-related conditions.

At Çatalhöyük, a large Neolithic site in Turkey that thrived around 9,000 years ago, numerous figurines of severely obese women have been unearthed. This irony highlights the shift in ancient societies, where obesity was seen as a symbol of fertility and prosperity, to its contemporary status as a medical and aesthetic issue that needs to be addressed, accompanied by the advancement of scientific technology throughout human history.

This article was originally published in Japanese in Iyakukeizai (Pharmaceuticals and Economics) on Oct 1, 2024.