GLP-1 has become a popular buzzword in the weight-loss community — but now some are touting “GLP-3s,” claiming they are taking obesity medications to the next level.

GLP-1 (glucagon-like peptide-1) medications work by mimicking a naturally occurring hormone in the body that helps regulate blood sugar and appetite.

The informal term “GLP-3” refers to a new triple-agonist drug that targets three hormones: GLP-1, GIP (glucose-dependent insulinotropic polypeptide, another naturally occurring hormone released by the gut after eating) and glucagon receptors. The most advanced example is retatrutide by Eli Lilly, according to clinical trial outcomes.

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The New England Journal of Medicine published results from a 2023 phase 2 retatrutide trial for obesity, revealing “substantial reductions in body weight” after 48 weeks of treatment.

A 12 mg once-weekly injection led to a 24.2% weight reduction, and participants continued to drop pounds after the 48-week trial period.

Side effects were reportedly similar to GLP-1 medications, most commonly including gastrointestinal complications like nausea, vomiting and diarrhea. Heart rate increases were noted, depending on the dose.

How it’s different

Retatrutide mimics three natural hormones found in the body, compared to GLP-1s that simulate just one hormone, according to a report by GoodRx pharmacists.

GIP and GLP-1 hormones signal the pancreas to release insulin after eating, while slowing digestion to help initiate feelings of fullness.

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These hormones target the area of the brain that regulates appetite and influences food cravings, the report noted.

The third hormone, glucagon, speeds up metabolism and helps the body break down fat cells for energy. That hormone also tells the liver to make new sugar, which is kept in check by GIP and GLP-1 activity, preventing blood sugar spikes.

“This added metabolism boost can add to and complement GIP’s and GLP-1’s actions. And that’s why it seems to provide significant weight loss,” the GoodRx website states. “If approved, retatrutide will be the first in a new class of medications.”

Eli Lilly announced results from its phase 3 trial TRIUMPH-4 in December, testing retatrutide’s effect on weight loss and other health conditions.

“We believe retatrutide could become an important option for patients with significant weight loss needs and certain complications.”

Participants with obesity and knee arthritis who took a 12-mg dose of retatrutide saw an average weight loss of 71.8 lbs (28.7%) at 68 weeks.

“For retatrutide, the findings from TRIUMPH-4 are encouraging, and with seven additional phase 3 readouts expected in 2026, we believe retatrutide could become an important option for patients with significant weight loss needs and certain complications, including knee osteoarthritis,” a Lilly spokesperson said in a statement to Fox News Digital. 

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The drug also reduced Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores by an average of 75.8%, marking “significant improvements” in comfort level and physical function.

More than one in eight patients reported being “completely free” from knee pain at the end of the trial, according to a press release from Lilly.

Seven additional phase 3 trials for retatrutide are expected to wrap up in 2026. The drug could see FDA approval in 2027, according to GoodRx.

The Lilly spokesperson noted that there have been no studies comparing retatrutide to GLP-1 treatments due to “differences in study design and patient populations.”

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Despite limited data availability on the drug, the medication could also be applied to treat other conditions like type 2 diabetes, kidney disease, cardiovascular risk reduction and metabolic dysfunction, according to GoodRx and other experts.

Fox News senior medical analyst Dr. Marc Siegel noted that Lilly’s Zepbound and Mounjaro already target two metabolic pathways — GLP-1 and GIP — which work together to promote weight loss, reduce hunger and inflammation, improve insulin function and slow digestion.

The doctor confirmed that the new drug, with its third receptor agonist, will further decrease hunger while increasing the feeling of fullness.

“The weight loss in clinical trials is even more substantial, and the most likely reason that it decreases orthopedic problems is because of the weight loss — less stress on the joints and the decreased inflammation,” Siegel added.

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The most common side effect of GLP-3s is gastrointestinal symptoms, the doctor confirmed. Rarer side effects may include pancreatitis, gallstones and heart arrhythmia.

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Philip Rabito, M.D., a specialist in endocrinology, weight loss and wellness in New York City, shared in an interview with Fox News Digital that this new class of weight-loss drugs is positioned to “approach bariatric surgery level outcomes” — although it doesn’t come without risks.

“The novel glucagon‑agonist component introduces less‑understood long‑term safety considerations, so it is imperative that patients are followed closely by healthcare professionals experienced with this class of medicines, with cautious, stepwise use, despite the impressive efficacy,” he cautioned.

The release of an updated food pyramid this week has sparked mixed reactions from doctors and dietitians.

One of the most noteworthy shifts in the 2025-2030 Dietary Guidelines for Americans — announced by HHS officials during a Jan. 7 press conference at the White House — is a greater emphasis on “high-quality proteins,” including red meat and eggs, as well as full-fat dairy.

The new guidelines focus on “real, whole, nutrient-dense foods,” and a dramatic reduction in highly processed foods, added sugars, refined carbohydrates and unhealthy fats.

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“Protein and healthy fats are essential and were wrongly discouraged in prior dietary guidelines,” Health Secretary Robert F. Kennedy Jr. said during the press conference. “We are ending the war on saturated fats.”

Nick Norwitz, a Harvard- and Oxford-trained researcher known for his work in metabolic health, shared his reaction to the new guidelines.

Despite how the new pyramid is presented, he noted, the actual guidelines for saturated fat consumption haven’t changed, as they still state that, “in general, saturated fat consumption should not exceed 10% of total daily calories.”

The intake of unprocessed whole foods rich in saturated fat, especially dairy fat, tends to be associated with improved health outcomes, according to Norwitz.

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“Full-fat dairy — especially cheese, for example — tends to be associated with lower BMI, reduced rates of diabetes and even reduced dementia risk,” he told Fox News Digital. “There are, of course, nuances — but ‘ending the war’ on saturated fat seems reasonable.”

Risks vary, experts say

Experts cautioned about the potential health risks of exceeding the recommended intake of saturated fat, including higher rates of LDL “bad” cholesterol, which is known to increase the risk of cardiovascular disease.

“The recommendation to limit saturated fat to 10% of total calories is based on the research showing that higher rates increase LDL cholesterol and associated risks for cardiovascular disease,” Sherry Coleman Collins, a food allergy dietitian and expert from the Atlanta metropolitan area, told Fox News Digital. 

Nutrition should be personalized and is dependent on multiple factors, she said, including age, gender, activity level and genetic risk factors.

“The total saturated fat an individual might safely consume is influenced by their size and total calorie needs, as well as potentially genetic differences,” Coleman Collins said.

Norwitz agreed, adding that “the specific food source and interaction with the unique host and their broader dietary context should take the spotlight.”

Dr. Pooja Gidwani, a double board-certified doctor of internal medicine and obesity medicine in Los Angeles, pointed out that not everyone has the same “tolerance” for saturated fats.

“If increasing saturated fat leads to a meaningful rise in LDL cholesterol or ApoB (Apolipoprotein B, a protein found on the surface of certain cholesterol-carrying particles in the blood), that intake level is excessive for that individual, regardless of improvements in weight or glucose metrics,” she said.

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“This personalized approach becomes increasingly important in midlife and beyond, when cardiovascular disease becomes the dominant driver of morbidity and mortality and when tolerance for cumulative atherogenic (artery-clogging) exposure is lower.”

For those who need to reduce LDL cholesterol or have a higher cardiovascular risk, the American Heart Association recommends an even lower amount of saturated fats — less than 6% of total daily calories.

Gidwani also cautioned that diets emphasizing saturated fat could crowd out fiber and unsaturated fats, “both of which play independent roles in cholesterol clearance, insulin sensitivity, gut health and inflammation.”

“Saturated fat-heavy patterns are also calorie-dense, which can quietly undermine long-term weight management if intake is not carefully regulated,” she added.

Not all saturated fats are equal, experts say

The effects of saturated fat depend on what specific foods are being consumed, according to experts.

“I would recommend choosing minimally processed or unprocessed forms of foods,” said Tanya Freirich, a registered dietitian nutritionist in Charlotte, North Carolina. “For example, in place of a hot dog — which has additives, nitrites, sodium and fillers — consuming a chicken thigh would be a much better choice.”

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Gidwani reiterated that the amount of processing plays a big role.

“Processed meats are consistently associated with worse cardiometabolic outcomes and represent the clearest category to limit,” she said. “The risk here is not only saturated fat, but also sodium load, preservatives and the broader dietary pattern they tend to accompany.”

Unprocessed red meat, the doctor said, can fit into an overall healthy diet in smaller amounts, particularly when consumed alongside fiber-rich plants and minimally processed foods.

“However, from a longevity perspective, it should be viewed as optional rather than foundational, especially for individuals with elevated cardiovascular risk,” she added.

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When it comes to dairy, Gidwani noted that fermented options are “metabolically more favorable” than butter or cream.

“However, saturated fat from dairy is still not necessary to prioritize for metabolic health or longevity,” she said. “Excessive reliance on dairy fat can displace healthier fat sources without offering clear long-term benefit.”

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Overall, the doctor recommends unsaturated fat sources, including extra virgin olive oil, nuts, seeds, avocado and omega-3-rich fish, as primary dietary fats.

“These consistently support lipid profiles, insulin sensitivity and vascular health,” Gidwani said. “Saturated fat can exist within a balanced diet, but it should remain secondary rather than emphasized.”

Why the big picture matters

Saturated fat is just one piece of a much wider nutrition puzzle, the experts agreed.

“Our heart health is not determined by one type of fat or one type of cholesterol, but the sum of many parts — our entire diet, our exercise habits, our stress and so much more,” Freirich said.

She recommends consulting a registered dietitian for guidance on unique dietary needs based on age, gender, activity level and medical history.

New Jersey-based dietitian Erin Palinski-Wade, author of “2-Day Diabetes Diet,” added that the message should be to focus more on overall patterns.

That means “plenty of fiber-rich plants, lean protein at every meal (including those that also contain fiber, such as nuts and seeds) and a reduction in overall intake of added sugars.”

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“That change will drive true health improvements,” she said.

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