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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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