With the use of anti-obesity drugs proliferating, the nutraceuticals industry has been positioning products to support those taking these new medications while other brands are seeking to offer natural alternatives for stimulating the GLP-1 hormone.

Industry experts at Natural Products Expo West offered a roadmap for companies to create supplements that have staying power in this market.

Brands seeking to offer solutions for an audience of consumers who are interested in or already taking a drug like Ozempic should understand shoppers’ pain points, the mechanism of action behind GLP-1 receptor agonist drugs versus supplements, and how to market a product effectively.

“GLP-1 is not really a fad. It’s been a hormone target for a while now, and while the weight loss industry has had a really bad rap with drugs in the past,” including prescription and over-the-counter options, “the science on GLP-1 is longstanding and much more well-understood from a safety standpoint,” said Stephanie Redmond, PharmD, founder and vice president of Dr. Stephanie’s Supplements.

Redmond noted that while insulin injections keep blood sugar in check, insulin therapy in the absence of lifestyle guidance has led patients to develop severe insulin resistance and gain weight.

“GLP-1s are the first drugs to reinforce positive lifestyle benefits by reducing cravings and body weight, and patients are often able to lower their insulin doses, and these benefits are happening fast,” she said. “As demand grows around new GLP-1 drugs, combination therapies involving them, and new health indications, this also presents an opportunity for the food and supplements industries to revive and remodel some product categories.”

Drugs vs Supplements

GLP-1 RAs have an effect on the hormone that no product classified as a food or a supplement can come close to replicating.

GLP-1, when released after eating food, lingers in the body for less than an hour before it’s broken down by an enzyme called DPP-4. GLP-1 RAs have a half-life of roughly one week, ensuring a steady release of the hormone, achieving steady-state plasma concentrations of the hormone several times greater than baseline. The few nutraceutical ingredients shown to impact steady-state GLP-1 concentrations increase the hormone by extremely modest amounts in comparison.

For that reason, marketing supplement products as analogs for these drugs is misguided at best. Targeting a broader impact on multiple hormones and biomarkers related to hunger could be more impactful. “As it relates to future hormone targets for dietary supplements, other hormones like amylin and leptin have been targeted by supplements in the past and probably will continue to be,” Redmond said.

“GLP-1 drugs work because they create a bombardment of a single molecule, and natural alternatives don’t tend to work that way. As a consequence, they have either fewer or no side effects. Lots of these products feature blends of ingredients, where the heavy lifting is done by one or two of the ingredients in the formulation,” noted Douglas Lynch, CEO of Marketwell Nutrition.

Understanding Consumer Needs

There’s a large target group of consumers who aren’t using GLP-1 drugs, but express interest in weight management and appetite control. Importantly, 50-85% of GLP-1 drug users stop taking them within a year or two, even though they’re indicated for indefinite usage, mostly due to side effects, inconvenience, affordability, and fear of long-term implications, Redmond noted.

These ex-users may be especially receptive to natural alternatives. Nutritional products can be especially helpful in mitigating the rebound effect, in which ex-users commonly regain the weight they lost but at a higher fat-muscle ratio.

Meanwhile, 67% of GLP-1 medication users have diabetes; only a minority of patients use these drugs strictly for weight loss, Redmond said, so the inclusion of diabetic care and blood sugar management ingredients shouldn’t be overlooked.

Marketing a Natural GLP-1 Booster

Lynch urged brands to lean heavily on the expertise of ingredient suppliers to effectively communicate the science behind ingredients in this space. “We can be the bridge for the brands; we bring them the GLP-1 technology, and we invest in the science. We can take things a step further and create a bridge between these brands and retailers with what we learn over the years it takes to develop these products,” Lynch said.

While a clinical study demonstrating a link between a supplement and increased GLP-1 usage can be relatively straightforward, marketing these findings comes with many familiar challenges. The specifics aren’t clear on what specific statements in this category will be considered disease-related claims by the U.S. Food and Drug Administration (FDA). Likewise, it’s likely that GLP-1 related marketing claims will be on the radar of the Federal Trade Commission (FTC).

When crafting a claim, “is ‘GLP-1 support’ enough to sell an ingredient to buyers? It’s going to get harder and harder to do that and you’ll need some differentiation along the way on why your claims stand out,” Lynch said. “It’s partly the job of the ingredient companies to help brands get the narrative down and make that pitch to retailers … and we help the brands find the right partners to talk to.”

Lynch, in consultation with supplier Ingredients by Nature, helped to market a lemon flavonoid called Eriomin, which was shown in three clinical studies to support measures of prediabetes including GLP-1 well before GLP-1 receptor agonists were being prescribed off-label for weight loss.

The company continued investing in studies to provide further substantiation linking the ingredient to a modest, naturally occurring GLP-1 boost while also supporting the ingredient’s safety and optimal dosage recommendations. Finally, the ingredient received a patent for the use of the flavonoid in stimulating GLP-1, providing critical IP protection.

“We find innovative ways to support our brands by putting them on panels, introducing them to buyers, and giving them everything they need,” Lynch said. “We find multinational partners who are champions in their respective fields, and two years ago we launched with three partners that each had different target audiences … It doesn’t hurt when you have a celebrity with hundreds of millions of followers on TikTok and Instagram. That someone was luckily looking at us too — that was Kourtney Kardashian, with her brand Lemme, who received requests over and over again for a GLP-1 product.”

These target consumers wanted a more modest GLP-1 boost in order to support more moderate effects compared to the pharmaceutical option, Lynch noted. “When we find partners who are great at telling a story to consumers, that’s when change really begins happening. When the only message [behind Eriomin] was prediabetes, we sold 3,000 kilos per year — nothing to be ashamed of. When we started talking about GLP-1, we sold 30,000 kilos in two years.”

Redmond noted that it’s not clear what kind of GLP-1 increase is considered to have a meaningful effect. “The jury is still out, so I always defer back to my pharmacy background,” she said. “Eriocitrin, for example, shows a fasting increase in GLP-1 concentrations of about 15-20%, and that’s especially meaningful because it’s not just a mealtime spike. You’re getting those benefits in a fasting state. But when you look at medications, like a DPP-4 inhibitor that selectively blocks the breakdown of GLP-1 in the body, that drug increases endogenous GLP-1 levels by two- or threefold, and that’s indicated for diabetes, not weight loss.” 

To maintain credibility, it’s important to set appropriate expectations about a product upfront, emphasize that it’s not a substitute for medication, and provide the timeline by which a beneficial effect has been observed, Redmond said.

“Not all things are equal” when it comes to a measured GLP-1 boost, Lynch noted. “There will be discussions about an ingredient’s effects on transient GLP-1 versus sustained GLP-1 concentrations,” and retailers will more frequently ask trickier questions to better determine the quality of the research behind a product.

Offering Nutritional Support for GLP-1 Users

“When the GLP-1 craze started to come up my team went to work trying to understand what it meant for us,” said Rachel Kreider, vice president of product innovation and science at GNC. “Everyone wanted us to try to mimic the effects of the drug. The more obvious side was nutrient deficiencies — you don’t just lose 50 pounds in a month without that happening, and there wasn’t much data on the dietary patterns of people taking these medications.”

According to an IRB-approved survey GNC conducted of people using these medications for weight loss, the average user consumed around 77 grams of protein per day, while needing an estimated 120 grams per day to preserve muscle mass. Further, there were extremely prevalent micronutrient deficiencies, such as vitamin D (99% of respondents), potassium (99%), magnesium (90%), and iron (88%).

Importantly, only 12% of respondents were given a recommendation to take a supplement, and 48% of respondents said they planned to use GLP-1 drugs indefinitely. “It’s scary that people are getting access to these medications with so little lifestyle advice,” Kreider said, and as a result, GNC has been focused on providing shoppers with in-person and online educational resources regarding nutritional needs of these shoppers. 

“If you’re losing muscle mass, your metabolism will slow and you’ll have to eat even less to maintain that decreased weight, which can lead to a rebound,” she added. “That’s where the big opportunity is for the food and dietary supplements industry … There are many protein, fiber, and probiotics products out there specifically formulated to be taken by a GLP-1 user, or products dealing with specific side effects. And multivitamins are a great add-on because when you’re not eating enough you need those nutrients.”

There’s still a strong market for products promising appetite control, weight loss, and a healthy blood sugar response, whether or not those products make a specific GLP-1 claim, Kreider noted. “We’re expanding what we do with weight loss products in our store, and again, it’s about weight loss and not management today, which is a good thing for all of us.” 

As people continue long-term use of these medications, there will be more awareness of the potentially severe loss of muscle mass as a side effect. “Creatine and HMB each have a lot of legs here; they’re so easy to add to a protein shake,” said Kreider.