Health
What are GLP-3s? Meet the new generation of weight-loss drugs with three key ingredients
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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.
GLP-1 (glucagon-like peptide-1) medications work by mimicking a naturally occurring hormone in the body that helps regulate blood sugar and appetite. (iStock)
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.
Participants in the phase 3 trial saw an average weight loss of 71.8 pounds. (iStock)
“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.
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. (iStock)
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.
More than one in eight patients reported being “completely free” from knee pain at the end of the trial. (iStock)
“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.
Health
GLP-1 Drugs Linked to Osteoporosis and Gout: Here’s How To Stay Safe
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Health
Ozempic-style drugs could slash complication risks after heart attacks, research suggests
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A popular class of weight-loss drugs may prevent life-threatening cardiac complications by opening microscopic blood vessels that often remain blocked after a heart attack, according to a study published this week in Nature Communications.
The research, led by the University of Bristol and University College London, identified a biological brain-gut-heart signaling pathway.
This discovery appears to explain how GLP-1 drugs — which mimic glucagon-like peptide-1, a hormone that helps regulate blood sugar and appetite — protect heart tissue from a condition known as “no-reflow.”
“In nearly half of all heart attack patients, tiny blood vessels within the heart muscle remain narrowed, even after the main artery is cleared during emergency medical treatment,” Dr. Svetlana Mastitskaya, the study’s lead author and a senior lecturer at Bristol Medical School, said in a press release.
“This results in a complication known as ‘no-reflow,’ where blood is unable to reach certain parts of the heart tissue.”
In nearly half of all heart attack patients, tiny capillaries (blood vessels) remain narrowed even after the main blocked artery is cleared. (iStock)
This lack of blood flow increases the risk of heart failure and death within a year. GLP-1 medications could prevent this, according to the researchers.
How it works
When the GLP-1 hormone is released in the gut or administered as a drug, it sends a signal to the brain, which then sends a signal to the heart that switches on special potassium channels in tiny cells called pericytes.
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When these channels open, the pericytes relax, which allows the small blood vessels (capillaries) to widen and improve blood flow to the heart muscle, the researchers noted.
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The new study used animal models and cellular imaging to track how GLP-1 interacts with heart tissue. When the researchers removed the potassium channels, the drugs no longer protected the heart — confirming they play a key role.
The findings suggest that existing GLP-1 medications, already used for type 2 diabetes and obesity, could be repurposed as emergency treatments. (iStock)
The findings suggest that existing GLP-1 medications, already used for type 2 diabetes and obesity, could be repurposed as emergency treatments during or immediately after a heart attack to reduce tissue damage.
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The researchers noted several limitations, including that the study relied on animal models.
Clinical trials are necessary to determine whether the brain-gut-heart pathway operates with the same timing and efficacy in humans.
While the study highlights the drug’s immediate benefits during a heart attack, it des not establish whether long-term use of these drugs provides a pre-existing level of protection. (iStock)
Additionally, while the study highlights the drug’s immediate benefits during a heart attack, it does not establish whether long-term use of the medication provides a pre-existing level of protection.
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The research was primarily funded by the British Heart Foundation.
Health
Do collagen supplements really improve skin? Major review reveals the truth
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Collagen supplements have exploded in popularity, touted as everything from an anti-aging miracle to a muscle recovery booster.
But a sweeping new review conducted by U.K. researchers suggests that while collagen may help improve skin elasticity and ease arthritis pain, it does little for athletic performance or wrinkle reduction.
Researchers from Anglia Ruskin University analyzed 16 systematic reviews and 113 randomized controlled trials involving nearly 8,000 participants worldwide, which they say is the most extensive evaluation of collagen’s health effects to date.
The review found consistent evidence that collagen supplementation improves skin elasticity and hydration over time and provides significant relief from osteoarthritis-related joint pain and stiffness, according to findings published in Aesthetic Surgery Journal Open Forum.
A large U.K. review found that collagen supplements may improve skin elasticity and hydration over time. (iStock)
The researchers, however, did not find meaningful improvements in post-exercise muscle recovery, soreness or tendon mechanical properties (strength, springiness and stretch resistance).
“Collagen is not a cure-all, but it does have credible benefits when used consistently over time, particularly for skin and osteoarthritis,” co-author Lee Smith, professor of public health at Anglia Ruskin University, said in a statement.
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“Our findings show clear benefits in key areas of healthy aging, while also dispelling some of the myths surrounding its use,” Smith added.
Collagen, the most abundant protein in the body, supports skin, bones, tendons, cartilage and connective tissue, according to experts. Natural collagen production begins to drop in early adulthood and declines more sharply with age.
The study found that collagen supplements may help reduce joint pain and stiffness in people with osteoarthritis. (iStock)
The review found that long-term collagen supplementation was linked to improved skin firmness and hydration, but did not help skin roughness — a proxy for visible wrinkles.
Benefits appear to accumulate gradually, suggesting that collagen should not be viewed as an “anti-wrinkle ‘quick fix,’ but as a foundational dermal support for individuals seeking holistic skin maintenance,” the researchers said.
“If we define anti-aging as a product or technique designed to prevent the appearance of getting older, then I believe our findings do support this claim for some parameters,” Smith told the BBC. “For example, an improvement in skin tone and moisture is associated with a more youthful-looking appearance.”
Collagen supplementation was linked to reduced pain and stiffness in people with osteoarthritis, with stronger benefits seen over longer periods of use, and showed modest improvements in muscle mass and tendon structure that may support healthy aging.
Collagen did not significantly improve skin roughness, a marker of visible wrinkles. (iStock)
However, it did not show meaningful results when used as a fast-acting sports performance supplement, and evidence for benefits related to cholesterol, blood sugar, blood pressure and oral health was mixed or inconclusive.
Dr. Daniel Ghiyam, a California-based physician and longevity specialist, said the findings align with what he sees in clinical practice.
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“Collagen is a targeted support tool, not a foundation of health or performance,” Ghiyam, who was not involved in the study, told Fox News Digital. “When marketed that way, it makes sense. When marketed as a cure-all, it doesn’t hold up to the data.”
The authors noted that while many previous collagen studies have received financial support from the supplement industry, the current review did not receive industry funding.
Experts say collagen supplements may offer modest benefits for skin hydration and joint comfort, but they are not a cure-all. (iStock)
The team called for more high-quality clinical trials examining long-term outcomes, optimal dosages and differences between collagen sources, such as marine, bovine and plant-based alternatives.
Among its limitations, the review could not determine whether certain forms of collagen work better than others or what the optimal regimen should be.
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While the review included randomized controlled trials, the quality of the studies varied, with newer research generally showing stronger results.
Experts say more data and studies are needed to build on the findings. They also noted that diet plays a crucial role in skin health.
Collagen supplements, often sold as powders or pills, may improve skin elasticity and ease joint pain, experts say. (iStock)
Dr. Erum Ilyas, a Pennsylvania-based dermatologist and chair of dermatology at Drexel University College of Medicine, noted that the review analyzed previously published meta-analyses rather than generating new primary data.
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“At this time, I have not seen sufficiently strong independent evidence to routinely recommend collagen supplements to my patients,” Ilyas, who was not involved in the review, told Fox News Digital.
“Although some studies show modest improvements in markers such as hydration and elasticity, there remains limited independent, biopsy-confirmed evidence demonstrating sustained increases in dermal collagen content,” she added.
Fox News Digital has reached out to the researchers for comment.
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