During a recent episode of her podcast, Gwyneth Paltrow spoke with neuroscientist Dr. Andrew Huberman about retatrutide, a new advancement in GLP-1 (glucagon-like peptide-1) therapies.

In recent years, GLP-1 receptor agonists have become a major focus in discussions around biohacking, longevity and wellness – but they’re not without a multitude of side effects.

Huberman noted that while first-generation weight-loss drugs curbed users’ appetites, they frequently plunged them into massive, rapid caloric deficits.

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Without aggressive resistance training, a high percentage of that lost weight came directly from lean muscle. “People would lose a ton of weight, but they would also lose muscle mass,” Huberman told Paltrow.

That is where retatrutide comes in, he said. Unlike older single- or dual-action medications, retatrutide is a triple agonist.

That means it activates the body’s receptors for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon – three hormones involved in regulating blood sugar, appetite and metabolism.

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“Retatrutide is a more mild agonist of GLP-1,” said Huberman. “It also increases glucagon and … GIP. So, it hits three different pathways, each a bit more subtly.”

In clinical trials, retatrutide is administered as a once-weekly subcutaneous injection.

Because of its balanced, multi-receptor approach, Huberman said the drug has a “lower side effect profile” while still allowing people to lose up to a third of their body weight “across a year or so.”

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Most importantly for fitness and longevity advocates, the doctor pointed out that retatrutide seems to have “some muscle sparing effect.”

Because the drug is still moving through official pipelines, a massive gray market of compounding pharmacies and online peptide suppliers has cropped up to meet the growing demand.

Huberman issued a strict warning regarding these unregulated online sources, noting that these options “can say 99% purity, but that 1% means there could be some LPS,” referring to lipopolysaccharides, a type of bacterial toxin.

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“LPS will cause inflammation,” he cautioned. “One injection isn’t gonna do it, but multiple injections over time, I could see where that could become problematic.”

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Paltrow echoed the safety concerns, comparing the current “wild-west” peptide craze to the landscape of supplements in the 90s, “where there’s really no third-party testing and it’s kind of word of mouth.”

“Multiple injections over time, I could see where that could become problematic.”

Both agreed that anyone exploring these therapies should avoid unverified online sources and prioritize working with a medical doctor.

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Retatrutide is an investigational molecule that is legally available only to participants in Lilly’s clinical trials, according to the manufacturer’s website. The company is currently “evaluating its safety and efficacy.”

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The drug has not been reviewed or approved by any regulatory agency, and no one should consider taking anything claiming to be retatrutide outside of a Lilly-sponsored clinical trial, experts advise.

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A new treatment for endometrial cancer demonstrated strong potential in a Phase 3 clinical trial.

Drugmaker Merck announced Monday that the investigational drug sacituzumab tirumotecan (sac-TMT) met its “primary endpoints” of overall survival and progression-free survival in patients with advanced or recurrent endometrial cancer.

The TroFuse-005 trial is the first global Phase 3 trial to “demonstrate statistically significant improvement” in survival compared to chemotherapy in these patients, according to a Merck press release.

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This was also the first and only antibody-drug conjugate (ADC) to achieve such a result for endometrial cancer patients in this setting, the researchers stated.

An ADC is a targeted cancer therapy that delivers more of the drug to tumor cells while limiting damage to healthy cells.

The trial involved 776 patients with endometrial cancer whose disease worsened after receiving both platinum chemotherapy and immunotherapy.

The patients were randomly assigned sac-TMT, administered every two weeks, or a treatment of the physician’s choice, including doxorubin or paclitaxel chemotherapy. The patients were aware of which treatment they were receiving.

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Those receiving sac-TMT showed “clinically meaningful improvement” in their disease state compared to the treatment of physician’s choice, the researchers found.

The study also met response rate benchmarks and exhibited similar side effects to earlier studies of the same drug, Merck reported.

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The drugmaker did not disclose any statistics on exact survival benefit, response rate, side effect rates or other details, but the researchers aim to present this Phase 3 data at an upcoming medical meeting.

Dr. Domenica Lorusso, the study’s global lead investigator and professor of obstetrics and gynecology at Humanitas University and Humanitas San Pio X in Milan, wrote in a press release that these results show sac-TMT “may be able to address a critical unmet need for certain patients with advanced endometrial cancer, one of the only cancers increasing in both incidence and mortality worldwide.”

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“Despite recent advances, patients whose disease progresses following treatment with platinum and immunotherapy are urgently in need of new options, and these findings show for the first time that a TROP2 ADC may be an effective option in this setting,” she added.

Dr. Brian Slomovitz, co-director of gynecologic oncology at Mount Sinai and an investigator on this trial, reflected on the study findings during an interview with Fox News Digital.

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“Unlike many other cancers that we are treating, the number of endometrial cancers and the number of deaths due to endometrial cancers are on the rise,” Slomovitz noted.

“In the United States, the number of deaths due to endometrial cancer has surpassed the number of deaths due to ovarian cancer, [making it] the deadliest of all gynecologic malignancies.”

Despite recent advancements introducing immunotherapy as the standard of care, “better treatment options” for patients with recurrent disease “remains an unmet need,” Slomovitz commented.

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“If the full data confirm this announcement, the key questions will be the magnitude of the survival benefit and the toxicity profile — those will define sac-TMT’s role,” he said. 

“But an overall survival improvement in recurrent disease is a real, meaningful result for patients and their families, not just a statistical one.”