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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.”
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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