Pharma's weight loss challenge: The incretin effect

Sept. 14, 2023
This three-part series will dig into incretin mimetics, their rise to fame in weight management and what it will take for the drug class to truly transform obesity care

From William the Conqueror’s alcohol-only regime in the Middle Ages to Lord Byron’s 19th century vinegar diet to Lucky Strikes’ ‘smoking for weight loss’ campaigns in the 1920s, history is heavy with questionable methods of weight management.

Ancient Greek physician Hippocrates, considered the ‘father of medicine,’ recognized excess weight as a health risk nearly 2,500 years ago, recommending lifestyle modifications such as diet and exercise. And according to Dr. Ethan Lazarus, past president of the Obesity Medicine Association, not much has changed in terms of modern-day treatment plans.

“The majority of doctors that I know still think that obesity is a function of willpower. I regularly have patients with BMIs as high as 50 or 60 who have been told that the treatment for their obesity should be eating more vegetables,” says Lazarus, who began his career in family medicine before taking over a specialized obesity management practice close to 20 years ago.

Despite the American Medical Association officially recognizing obesity as a disease in 2013, medical and societal stigma has persisted — and so has obesity. Today, more than two-thirds of U.S. adults are either overweight or obese — a growing problem that adds over $170 billion to the country’s health care costs each year.

It’s an epidemic that has long lacked safe and effective pharmacologic solutions — until now.

A fast-growing class of drugs known as incretin mimetics, originally developed to treat type 2 diabetes, may rewrite the script for obesity care.

“These drugs are not silver bullets,” warns Dr. Marcus Schabacker, president and CEO of ECRI, a global independent authority on health care technology and safety. “Obesity is a multifactorial issue and you need to take a multifactorial approach, but in that context, the drugs are very effective and could truly be a turning point.”

Faced with a sizable potential patient population and a global market now projected to hit $100 billion in sales by 2030, pharma has the opportunity to raise the missing pillar in comprehensive obesity care.

But there’s a hefty caveat. Treatment options come with a high price tag and right now, pickings are slim. So slim that Novo Nordisk currently owns the entire incretin obesity market with the only two FDA approved drugs. In the absence of options, off-label demand for incretin-based diabetes treatments, specifically Novo’s Ozempic and Eli Lilly’s Mounjaro, has triggered ongoing shortages.

The hunger for Novo Nordisk’s pricey new anti-obesity drug, Wegovy, is so great that the drugmaker’s CEO recently said it could take “some years” for the company to meet the demand. Even as the drugmaker scrambles to fill orders, lack of competition has padded its pockets; Novo Nordisk is now valued more than the entire Danish economy.

Continued momentum in obesity care will be predicated on access to new drugs. In order to truly transform obesity into a treatable disease for all patients, pharma must overcome current supply and pricing issues and get more drugs through development and within reach of those who need them most.

The incretin effect

While they don’t date back to antiquity, incretin mimetics are not as new as their recent TikTok popularity implies.

The term ‘incretin’ is credited to Belgian physiologist Jean La Barre, who in 1932 proposed that diabetes could be treated with naturally occurring human hormones. The two main incretin hormones released by the small intestines, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), were officially identified back in the 1970s and 1980s, respectively.

In what is now known as the ‘incretin effect,’ scientists discovered that in healthy individuals, glucose responsive receptors in the gastrointestinal tract trigger the release of GIP and GLP-1 hormones in response to food — but in people with type 2 diabetes, this effect is blunted.

From those new advances in diabetes understanding came the idea that long-acting stable receptor agonists of the GLP-1 hormone could be used to stimulate insulin secretion. As their name implies, incretin mimetics work to mimic the glucose-lowering actions of incretins.

In 2005, the FDA approved the first incretin mimetic, developed by Amylin Pharmaceuticals and Eli Lilly, as an add-on therapy for patients with type 2 diabetes. By binding to GLP receptors in the pancreas, the drug, branded Byetta, triggered the effects of the GLP-1 hormone.

Byetta’s weight loss properties, which were consistently demonstrated in clinical trials, were used to position the drug against other type 2 diabetes drugs, many of which were commonly associated with weight gain. But Byetta’s ability to stimulate weight loss set the stage for the exploration of incretin mimetics in obesity care.

Continue reading Part 2: Pharma's weight loss challenge: Nourishing an obesity market

Download the full pdf here

About the Author

Karen P. Langhauser | Chief Content Director, Pharma Manufacturing

Karen currently serves as Pharma Manufacturing's chief content director.

Now having dedicated her entire career to b2b journalism, Karen got her start writing for Food Manufacturing magazine. She made the decision to trade food for drugs in 2013, when she joined Putman Media as the digital content manager for Pharma Manufacturing, later taking the helm on the brand in 2016.

As an award-winning journalist with 20+ years experience writing in the manufacturing space, Karen passionately believes that b2b content does not have to suck. As the content director, her ongoing mission has been to keep Pharma Manufacturing's editorial look, tone and content fresh and accessible.

Karen graduated with honors from Bucknell University, where she majored in English and played Division 1 softball for the Bison. Happily living in NJ's famed Asbury Park, Karen is a retired Garden State Rollergirl, known to the roller derby community as the 'Predator-in-Chief.'