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What are GLP-3s? Meet the new generation of weight-loss drugs with three key ingredients

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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.

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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)

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“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.

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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.

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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.

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Study challenges negative cannabis stereotypes, claiming link to brain benefits

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Study challenges negative cannabis stereotypes, claiming link to brain benefits

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While cannabis has recently come under fire for potential negative health risks, a recent study suggests that its use could increase brain volume and cognitive fitness.

Researchers at the University of Colorado Anschutz Medical Campus analyzed cannabis usage, brain scans and cognitive test results for more than 26,000 adults between the ages of 40 and 77, using data from the UK biobank.

The study found that cannabis users — particularly those who reported moderate lifetime usage — showed larger volumes in several brain regions.

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“Compared to individuals with no history of cannabis use, those who reported using cannabis showed larger volumes in several brain regions characterized by a high density of cannabinoid (CB1) receptors — regions involved in processes such as memory, information processing and emotion regulation,” lead study author Anika Guha, Ph.D., a researcher at the University of Colorado Anschutz Medical Campus, told Fox News Digital.

A recent study suggests that cannabis use could increase brain volume and cognitive fitness. (iStock)

The cannabis users also scored better on cognitive tests that measured learning, processing speed and executive function. 

This outcome differs from many previous studies, which have focused on short-term cognitive impairment during or shortly after cannabis use, the researcher pointed out.

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“These findings suggest that the relationship between cannabis and the brain may differ across the lifespan, and that moderate use in mid-to-later adulthood may be associated with positive brain health outcomes,” Guha said.

Not all areas of the brain showed positive effects among cannabis users. The posterior cingulate, which is involved in self-reflection and memory, had lower volume with higher marijuana use.

“The takeaway is not that people should start using more cannabis based on these findings alone.”

As cannabis has been rising in popularity among all ages, this type of study is important for understanding its long-term effects and the pros and cons of use, according to Matt Glowiak, Ph.D., chief addiction specialist with Recovered, an organization that provides information and resources for mental health and addiction treatment.

The drug’s effects likely depend on factors such as age, dose, frequency, product composition and individual vulnerability. (AP Photo/Martin Meissner, File)

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“Given the connection between cannabis use and larger brain volume, it is believed that it may help [older] individuals retain cognitive function that might otherwise naturally decline,” Chicago-based Glowiak, who was not involved in the study, told Fox News Digital.

“This is a huge benefit, but one we need to explore a bit further, ahead of encouraging those who would otherwise not consider integrating cannabis into their healthcare regimen.”

Limitations and caveats

As the study was observational in nature, it could not prove that cannabis use improves brain health — instead, it only showed an association, according to Dr. Marc Siegel, Fox News senior medical analyst, who was not involved in the study.

“The preponderance of previous evidence does not line up with improved cognitive function from chronic cannabis use,” Siegel told Fox News Digital. “This study is an outlier, and though it cannot be ignored, it is not justification for use.”

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The study also relied on the UK Biobank, which offers a “large and rich dataset,” Guha said — but it is limited to the questions that were originally posed to the participants.

“In particular, we have only a broad measure of how many times someone has used cannabis over their lifetime,” she said. “We do not have access to details about how they used cannabis, such as whether they smoked or used edibles, the type or potency of cannabis, or when in their life they used most heavily.”

Cannabis users scored better in learning, processing speed and executive function. (iStock)

“Those details likely matter a great deal for understanding how cannabis affects the aging brain.”

Given these limitations, Guha suggests that the findings should be seen as an early indicator that cannabis use may be related to brain aging, “and as a starting point for more targeted research that can tease apart these relationships.”

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“The takeaway is not that people should start using more cannabis based on these findings alone,” she emphasized. “While cannabis may have potential benefits in some contexts, a substantial body of research also documents important risks, underscoring that cannabis is neither completely beneficial nor completely harmful.”

The drug’s effects likely depend on factors such as age, dose, frequency, product composition and individual vulnerability, according to Guha.

“Given the widespread use and legalization of cannabis, it would be great to know that it is net-positive for brain health — however, this feels too good to be true, and too early to claim,” one expert said. (AP)

“As with any substance, individuals should consult with a healthcare provider before initiating use, particularly if they have a history of mental health concerns, as THC (the primary psychoactive component of cannabis) can exacerbate symptoms such as psychosis in vulnerable individuals,” she added.

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Dr. Alex Dimitriu, who is double board-certified in psychiatry and sleep medicine and the founder of Menlo Park Psychiatry & Sleep Medicine, reiterated that this study is an “outlier,” as most previous research has shown “detrimental effects” from cannabis use. 

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“Given the widespread use and legalization of cannabis, it would be great to know that it is net-positive for brain health — however, this feels too good to be true, and too early to claim,” he said. “I would advise proceeding with caution and moderation.”

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Dimitriu agreed that more large-scale studies and review papers are needed to get a “clearer picture.”

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“What this cannabis study shows is that there may be conflicting information, which warrants more investigation.”

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‘Fire-breathing’ trend linked to severe burns in teens, officials warn

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‘Fire-breathing’ trend linked to severe burns in teens, officials warn

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Parents are being warned of a new trend among kids, involving alcohol and an open flame.

The “fire-breathing” challenge has led to reports of severe burns, according to local news outlets.

Kids and teens are reportedly holding alcohol in their mouths and blowing it onto a match or another open flame to mimic “breathing fire.”

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According to Philadelphia’s 6ABC News (WPVI), a teen in Pitcairn, Pennsylvania, was intubated and treated for burns to the face, neck and chest after attempting the trend.

A “fire-breathing” challenge is leaving kids with severe burns, according to local reports. (iStock)

“Luckily, in this particular case, it did not burn the building down,” Al Hussey, Wilmerding Borough fire marshal, told WPVI.

“But somebody really got hurt, and, you know, is going to have life-altering injuries.”

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Pitcairn Fire Chief Tommy Dick told CBS News Pittsburgh (KDKA) the 14-year-old girl was playing with isopropyl alcohol at an apartment complex.

“It’s not a very smart thing for anybody to do, let alone children,” Dick said. “It’s supposed to be for cleaning off wounds and cuts and stuff, not ingesting and trying to blow fire.

A local fire chief told CBS News Pittsburgh that the incident could have been fatal for the teen. (iStock)

“This could have easily gone inside their digestive tract, and she could have died.”

Anyone who has ingested isopropyl alcohol requires immediate medical attention, according to Healthline, because it can cause stomach pain, dizziness, confusion and slowed breathing. In severe cases, it can lead to a coma.

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Fire experts are urging parents to closely monitor which household products are within their children’s reach.

Ingesting isopropyl alcohol requires immediate medical attention, according to experts. (iStock)

“If they’re doing their hair with chemicals, if they’re taking isopropyl alcohol in the room or any type of fingernail polish remover,” Hussey said. “Obviously, monitor your lighters and your matches and educate your children.”

Multiple cases of children’s injuries have occurred in recent weeks after being allegedly “inspired” by online stunts, WPVI reported. One trend involved microwaving a toy that burst and left severe burns on a 9-year-old’s face.

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Ancient herb known as ‘nature’s Valium’ touted for improving sleep and anxiety

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Ancient herb known as ‘nature’s Valium’ touted for improving sleep and anxiety

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Valerian, an herbal supplement long used for sleep and relaxation, has been referred to as “nature’s Valium” — but experts are divided on whether it truly compares to the prescription sedative.

The herb, which is sold as a dietary supplement in the U.S., is a common ingredient in products marketed as “mild sedatives” and sleep aids, according to the National Institutes of Health. 

Valium, the brand name for diazepam, is used to treat anxiety, seizures and muscle spasms by calming the nervous system, Cleveland Clinic notes.

Valerian supplements are derived from the roots of Valeriana officinalis, a flowering plant native to Europe and Asia that has also naturalized in northeastern America, according to the American Botanical Council (ABC).

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The plant has a “long history of medicinal use,” per the ABC, with the primary goal of reducing anxiety and stress as well as improving sleep quality. It has historically also been used for migraines, fatigue and stomach cramps.

Valerian has historically been used for migraines, fatigue and stomach cramps. (iStock)

Dried valerian roots can be prepared as teas or tinctures, while other plant materials and extracts have been distributed as capsules or tablets, per the NIH.

The agency noted, however, that there is a “relatively small amount of research” investigating the herb’s impact on various conditions.

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However, Stefan Gafner, Ph.D., chief science officer of the American Botanical Council in Texas, confirmed that some clinical trials have explored valerian root’s effects.

A 2020 medical review published in the Journal of Evidence-Based Integrative Medicine found that both powdered root and root extracts show a “clear” benefit in treating anxiety, Gafner told Fox News Digital.

Valerian root and other parts of the plant can be prepared as teas, extracts, capsules and tablets. (iStock)

The researchers concluded that valerian could be a “safe and effective herb to promote sleep and prevent associated disorders.”

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While valerian may have some benefits, Gafner said he doesn’t think it “makes sense” to compare it to diazepam (Valium). 

“I can understand that both are used to relieve anxiety, but valerian is a much milder ingredient, and is really used for mild cases of anxiety and sleep issues,” he told Fox News Digital.

Some valerian users have reported improved sleep and reduced anxiety, according to recent research. (iStock)

Unlike valerian, diazepam carries a risk of dependence and is generally prescribed short-term, the expert said, and the spectrum of potential adverse effects is “very different.”

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Gafner said he “absolutely” recommends the use of valerian root to relieve anxiety and stress and to improve sleep.

“I have used it myself and I believe it’s an ingredient with well-documented benefits, especially for people with problems falling asleep,” he said. “It is well-tolerated and very safe… although some sources caution [against] driving a car or using heavy machinery when using valerian.”

Valeriana officinalis, a herbal plant used as a mild sedative, in bloom. (iStock)

Dr. Joseph Mercola, a board-certified family medicine osteopathic physician and author of the new book “Weight Loss Cure,” said valerian’s comparisons to Valium may “exaggerate what the science actually shows.”

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“Valerian root contains compounds that appear to enhance calming brain chemicals, particularly the neurotransmitter GABA, which helps quiet nerve activity and supports relaxation,” the Florida-based expert told Fox News Digital.

“Some studies do report modest improvements in sleep quality or shorter time to fall asleep, while others find no meaningful difference compared with placebo.”

Valerian supplementation may not be right for everyone seeking better sleep, one doctor said. (iStock)

Side effects may include headaches, dizziness, digestive upset or next-day grogginess, Mercola noted, adding that he would not recommend it as a primary strategy for anxiety, stress or sleep.

“Because long-term safety studies remain limited, and supplement quality varies widely, you should approach valerian with caution rather than view it as a universal sleep solution,” he advised.

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“You should approach valerian with caution rather than view it as a universal sleep solution.”

“I encourage people to focus first on strategies that correct the underlying drivers of poor sleep,” Mercola advised. “When you fix those foundations, you often find that you no longer need an herbal sedative at all.”

“I encourage people to focus first on strategies that correct the underlying drivers of poor sleep,” one doctor advised. (iStock)

“Bright sunlight during the day helps regulate your circadian rhythm and signals your brain to produce melatonin later at night,” he said. “At the same time, complete darkness [at night] supports the hormonal signals that allow deep, restorative sleep.”

Certain nutrients can also promote relaxation and sleep quality, including magnesium, which helps to regulate the nervous system, according to the doctor.

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GABA may help to calm nerve activity, reduce stress markers and improve perceived sleep quality, Mercola said, while glycine — taken at about 3 grams an hour before bed — may support relaxation, promote the body’s nighttime temperature drop, and improve sleep onset and overall quality.

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“When you combine sunlight exposure, magnesium, GABA and glycine, you support the biological systems that control sleep instead of relying on a sedating herb with mixed evidence,” the doctor concluded.

Fox News Digital reached out to valerian root manufacturers requesting comment.

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