New GLP-1 science and drugs reach “tipping point,” reshaping health and nutrition

Emerging science and drug product development are poised to transform the US GLP-1 landscape, potentially increasing the adoption of these medications even further. Researchers are exploring how organs beyond the gut secrete GLP-1 and other satiety hormones, and how nutrition may impact this system. Meanwhile, the pharmaceutical pipeline is expanding rapidly into new indications, hormone combinations, and more convenient delivery formats. 

At the recent Discovery Forum on precision nutrition in the GLP-1 era, organized by the University of California (UC) Davis, US, we caught up with a metabolic health researcher and the program director at the Innovation Institute for Food and Health (IIFH). 

“This is a tipping point,” Kim Fisher, director of programs at the UC Davis IIFH, tells Nutrition Insight.

“I think these drugs will change how we think about taking weight control medications. In the ‘70s, there were many problems with diet drugs, and then we moved away from them,” she adds. “But now, these GLP-1 drugs are opening up other types of medications, mechanisms of action, and opportunities to help people manage their weight that weren’t getting into the pipelines before.”

In addition, she notes that Ozempic, a semaglutide-based medication from Novo Nordisk, is set to go off patent in the EU, China, and Canada next year, and in the US in 2032. This means generic versions could enter the market, resulting in more competition and lower prices. Earlier this year, the US low-cost retailer Costco partnered with Novo Nordisk to sell Ozempic and Wegovy in its pharmacies at a reduced cost.

“GLP-1s and related metabolic hormones are very powerful, but I think we haven’t really begun to touch other indications,” says Fisher. “We have so much to learn about how they can impact all these other disorders.”

Dr. Bethany Cummings, a professor at UC Davis School of Medicine, agrees that the GLP-1 field is undergoing “a revolution,” as it is shifting away from the idea that GLP-1 is primarily secreted from the gut.

At the recent Discovery Forum, Fisher highlighted market and trial developments in GLP-1 medications (Image credit: Marissa Pickard / IIFH). “GLP-1 is also made in neuronal populations in the brain and under certain circumstances by alpha cells [in the pancreas]. This local production of GLP-1 can interact directly with surrounding cells to elicit these beneficial effects.”

“We have a great understanding of metabolic regulation from a glucose-centric point of view, but when it comes to other macronutrients, our understanding vastly dissipates,” she underscores. “My lab is interested in amino acids and understanding how they regulate GLP-1 secretion from the gut, as well as how they influence GLP-1 secretion in alpha cells.”

Amino acid variations 

According to Cummings, there is a gap in understanding how other macronutrients manipulate these alpha cell types, with certain amino acids being “a far greater stimulus” for hormone secretion from these islets than glucose.

“My lab is focused on understanding the effects of GLP-1 on the pancreatic islet. We’re interested in the idea of reprogramming alpha cells to produce GLP-1, which is a very attractive therapeutic target. We’re specifically looking at how amino acids regulate alpha cell biology.”

“We have some molecular triggers that can activate GLP-1 production in the alpha cells and are conducting studies where we dose mice with different amino acids acutely to see how that affects the islet.”

The results so far are “mind blowing,” says Cummings. For example, her team compared glucose alone versus glucose with the amino acid arginine, and the hormone secretion from the islet in response to the combination was much higher than with glucose alone. “This is some basic biology that could ultimately inform nutritional approaches and treatments.”

“Endogenous GLP-1 production will never match the levels seen with drugs, but it’s still important and can have a metabolic benefit with fewer side effects. It might even inform better pharmacology in the future.”

Cummings is investigating how to complement the internal GLP-1 system with interventions to achieve better outcomes with fewer side effects. Cummings is investigating how to complement this internal GLP-1 system with pharmaceutical and nutritional interventions to achieve better outcomes with fewer side effects. “The alpha cell aspects, in my dream world, lead to a drug that can activate the GLP-1 pathway, but also nutritionally make recommendations that can adjust that pathway.”

Pharma market offering

Currently, there are five main drugs on the market, explains Fisher.

“There are two GLP-1s, one for obesity, one for weight loss; two tirzepatides, which are combination GLP-1 and gastric inhibitory polypeptide (GIP) drugs, one for obesity and one for weight loss; and then one pill, Rybelsus. This daily pill hasn’t had much uptake because you need to fast for an hour before you take it and drink a lot of water, so it’s a hassle.”

She notes that there are many developments in the market. “Already in the last year, we saw new indications for cardiovascular disease, kidney disease, and sleep apnea, for example.”

Ozempic’s patent expiring will also have a major impact as price is a significant restraining factor for people, details Fisher. “Once these medications become more affordable, we’ll also see a higher uptake. We’re just at the start of this. Even though we’re early on, 6% of Americans are already taking these drugs, and 12% have taken them at some point. That’s 20–40 million people just in the US, so this is just the tip of the iceberg.”

She adds that the leading market players in GLP-1 medications are Novo Nordisk and Eli Lilly, and these companies may not want to develop products for smaller indications, such as type 1 diabetes, as their primary business focuses on obesity and type 2 diabetes.

“As we see different medications, combinations, and indications, we’ll see more early-stage and other pharma companies entering the fray.”

New product development

Fisher highlights three key areas of product development in GLP-1 medications: combination therapies, enhancing ease of use, and expanding indications.

Pharma product development in GLP-1 focuses on combination therapies, enhancing ease of use, and expanding indications.“We already know where the shifts are happening,” she details. “There are more than 100 things in clinical studies, with over 40 in the final phase, phase three of clinical studies. In the next year or two, we’re going to see so much more on the market.”

Currently, the market offers some combinations of GLP-1 and GIP hormones in tirzepatide medications, but she expects more new combinations to enter the field.

“We’ll have GLP-1, GIP, amylin and insulin, or amylin and glucagon combinations,” she predicts. “The benefit to the patient and consumer of these combinations, like you’re already seeing in tirzepatide, has fewer side effects than GLP-1s. They’re also more impactful.”

“You’ll see people can take less of these drugs because they’re so powerful and then also reducing adverse effects because of different mechanisms of action from these metabolic hormones.”

Additionally, she anticipates that more medications will be developed to target numerous new indications. “There’s a clinical study on knee osteoarthritis pain, and studies for Alzheimer’s disease and type 1 diabetes.”

“As these drugs impact different body systems, there are clinical studies on addiction disorders. I think these drugs are going to be available for more than just obesity and type 2 diabetes.”

Lastly, she expects new drugs to be easier to consume. “There is a pill in phase three clinical studies that won’t require fasting or drinking a lot of water. There are also monthly injections in clinical studies. There are weekly pills being developed, although these are earlier in clinical studies, so we won’t see that in the next year or two.”

“As these things are easier to take, we’ll see even more uptake,” she notes.

Fisher expects new drugs to be easier to consume, as there is a pill in clinical trials that won’t require fasting or drinking a lot of water. Moreover, she highlights that some people using these drugs to manage glucose levels don’t want to lose any weight, for example, if they take medications for type 1 diabetes or addiction disorders. 

Nutritional impact

Already, anti-obesity and metabolic health medications, such as GLP-1 receptor agonists, have a significant impact on the nutrition industry, with companies developing solutions to complement these drugs or mitigate side effects. 

“People on these medications are eating less, but they’re still eating — just differently. The overall impact on the food industry is tremendous,” says Fisher.

She notes that food companies are also increasingly approaching IIFH to create healthier, yet tasty, food products with the institute. “This could be a moment of change, where we eventually go back to having better food choices and reduce the need for these medications.”

“My dream would be that this gets so big and impacts how people are developing food so that our food system is healthier and people won’t need these medications as much,” she adds.

Fisher points to a 2022 study indicating that 93% of US adults are metabolically unhealthy, based on assessments of adiposity, blood glucose, blood lipids, blood pressure, and clinical cardiovascular disease.

“There was a time when we just wanted to make sure people got food. Now, we’ve reached a point where the food choices available to us in grocery stores aren’t the best, and I think it’s time for a change.”