How Research to Treat Diabetes Led to the Discovery of an Effective Weight Management Drug

In 1970, Norman Borlaug won the Nobel Prize for being the “Father of the Green Revolution.” In the 20th century, over seventy million people died of famine worldwide, with the majority of those deaths occurring prior to 1960. World wars and political instability contributed to those deaths, but outdated farming methods were the primary drivers of famine. Starting in Mexico in 1940, the Green Revolution was a multinational effort to implement newly hybridized seeds (mostly for grain), pesticides, and synthetic nitrogen fertilizers. Today, worldwide famine has been largely eliminated, but we now face the problems of calorie overabundance, obesity, diabetes, and heart disease, which are now the major causes of death and physical suffering worldwide. 

Interestingly, as is often the case in human events, major advancements in technology created unintended consequences. 

As the Green Revolution was taking off, scientists began studying the biologic mechanisms of diabetes. All diabetes, whether type 1 or 2, involve dysfunction of insulin metabolism. Type 1 diabetes is caused by the destruction of insulin-producing cells in the pancreas, resulting in a lack of insulin. In Type 2 diabetes, insulin production is intact, but the body does not process insulin sufficiently. This process is made worse by obesity, which exacerbates insulin sensitivity and leads to an overall inflammatory state. 

For decades, we’ve been able to treat diabetes through a variety of medications and lifestyle changes, but obesity has remained tricky to manage. Diet and exercise often aren’t enough to help us achieve a manageable weight, as our brains get used to a certain set-point of body weight. Fat shaming definitely doesn’t work as a weight-loss tool. Arguably, the greatest developments in managing obesity are a class of drugs called glucagon-like peptide-1 agonists (GLP-1A). One of the highest awards in medicine was given to Svetiana Mojsov, the scientist who discovered glucagon-like peptides. In the early 1980s, she sequenced GLP-1, which stimulates the pancreas to release more insulin. Then her team injected GLP-1 into rat brains. What they found has led to the greatest advancement in weight management since, well, famine. The rats injected with GLP-1 lost their appetite and lost weight while also improving their insulin regulation. 

Naturally made GLP-1 couldn’t be used as a medicine as it was metabolized rapidly and required a twenty-four-hour infusion. Scientists added a fatty-acid chain to GLP-1 to make it last longer in the body. This led to the FDA approval of liraglutide in 2010, then subsequently, semaglutide and tirzepatide. Patients can lose 15 to 20 percent of their weight with GLP-1 agonists—and keep it off—while also treating diabetes. 

This is an astounding feat of human accomplishment. No other class of drugs has so many wide-ranging applications. We’re finding that GLP-1 may have long term benefits for obesity, insulin production, heart disease, liver failure, and substance abuse, among others.

The Green Revolution led to the Fast Food Nation, which has now ushered in the Era of “Weight-be-Gone with Glucagon.”