Thank you for listening to The Peptide Podcast. If you enjoyed the show and want to support what we do, head over to our <a href="https://pepties.com/partners/">Partners Page</a>. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going.  Today we’re switching gears a bit to talk about a medication rather than a peptide — metformin. If you’re someone who’s interested in <a href= "https://pepties.com/mots-c-peptide-therapy/">peptides for metabolic health</a> or <a href= "https://pepties.com/understanding-the-healing-potential-of-bpc-157-peptide-therapy/"> inflammation</a>, you’ve probably heard metformin mentioned alongside them. It’s been around for decades as a diabetes medication, but recently it’s gaining attention for its potential benefits beyond blood sugar, including longevity, inflammation, and neuroprotection — even in people who don't have diabetes. Let’s get into it. Metformin and Longevity Can metformin really help us live longer? One of the biggest sparks came from a 2014 study published in Diabetes, Obesity and Metabolism, where researchers found that diabetics on metformin actually <a href= "https://pubmed.ncbi.nlm.nih.gov/25041462/">lived longer</a> than non-diabetics not taking the medication.  The authors suggested that metformin may offer protective benefits beyond glucose control, possibly by reducing oxidative stress and slowing cellular aging. This inspired the launch of the <a href= "https://www.afar.org/tame-trial">TAME trial</a>—short for Targeting Aging with Metformin—which is designed to test whether metformin can delay the onset of age-related diseases like cancer, cardiovascular disease, and cognitive decline. While results are still pending, it’s the first large-scale effort to study aging as a treatable condition, not just a process. Inflammation and Immunometabolism Next up: inflammation. Chronic low-grade inflammation is at the root of so many health issues—heart disease, dementia, even depression. Metformin appears to blunt systemic inflammation by activating AMPK. Think of AMPK as a metabolic master switch that lowers inflammatory signaling. A <a href= "https://pubmed.ncbi.nlm.nih.gov/34570348/#:~:text=of%20Multiple%20Sclerosis-,Metformin%20Therapy%20Attenuates%20Pro%2Dinflammatory%20Microglia%20by%20Inhibiting%20NF%2D%CE%BAB,Epub%202021%20Sep%2027."> 2021 review</a> published in Pharmacological Research found that metformin can inhibit NF-κB, a major pathway that drives inflammation. It also helped lower levels of CRP—a protein made by the liver that rises when there’s inflammation from things like infection, injury, or chronic disease—and IL-6, another immune system protein commonly elevated in chronic inflammatory conditions. Because of these anti-inflammatory effects, researchers have been exploring metformin’s potential in conditions beyond diabetes, including autoimmune diseases, multiple sclerosis (MS), PCOS, and even COVID—where it’s been linked to lower mortality in patients with diabetes. Brain Health and Neuroprotection What about the brain? Can metformin help protect against cognitive decline? There’s some promising data here too. A <a href= "https://pubmed.ncbi.nlm.nih.gov/28766905/">2017 study</a> in Aging Cell found that metformin improved neurogenesis in the hippocampus of aged mice—basically, helping old brains grow new neurons. In 2019 a <a href= "https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2810994#:~:text=Metformin%20may%20also%20reduce%20dementia,10"> cohort study</a> in JAMA Network reported that people with type 2 diabetes taking metformin had a lower risk of developing dementia compared to those not taking it. Mechanisms may include reduced <a href= "https://pepties.com/insulin-resistance-men-vs-women/">insulin resistance</a> in the brain, less oxidative stress, and—again—AMPK activation, which promotes mitochondrial health and energy production. Still, human trials are mixed, and more controlled research is needed before we can call it a “smart drug.” Lower Cancer Risk So, here’s an interesting one—can metformin actually lower the risk of cancer? Well, the short answer is: maybe. People with diabetes tend to have a higher risk of developing certain types of cancer, so part of metformin’s benefit could just come from better managing blood sugar and insulin levels. But what’s really exciting is that researchers think metformin might do even more than that. There’s evidence suggesting it could have direct effects on cancer cells—like slowing down their growth or making the environment less friendly for tumors. Some studies have found lower rates of cancers like breast, colon, and prostate in people taking metformin. Now, this isn’t a magic bullet or anything, but it’s a promising area of research that’s getting a lot of attention. So metformin might be pulling double duty: managing diabetes and potentially helping reduce cancer risk through other mechanisms we’re still learning about. Metabolic Health for Non-Diabetics Now here’s where it gets controversial—should healthy people without diabetes be taking metformin? Some researchers argue yes, especially for people with metabolic syndrome, prediabetes, or high inflammation. Metformin improves <a href= "https://pepties.com/building-an-insulin-sensitive-lifestyle/">insulin sensitivity</a>, reduces liver glucose production, and may even support modest weight loss. That said, there are tradeoffs. Metformin can cause stomach-related side effects (e.g., nausea, gas, heartburn, and diarrhea) and vitamin B12 deficiency (which may lead to nerve damage). It can also cause extreme fatigue.  Metformin may sometimes cause sexual side effects, like erectile dysfunction in men. Some studies suggest it might lower testosterone, which we know is important for male sexual health. But interestingly, other research points to metformin actually improving blood flow to the penis, which could help with erectile issues. So, it’s a bit of a mixed picture—and it really depends on the individual. And although rare, it can cause lactic acidosis (a life threatening condition where lactic acid builds up in the blood) in older adults, people with advanced kidney disease, or those who drink excessive amounts of alcohol. So it’s not a free pass.  So what are my final thoughts and who should you take metformin for longevity? Metformin isn’t a one-size-fits-all solution, and it’s definitely not something to start just because you heard about it on a podcast. We still need more research—especially in people without diabetes—to really understand who benefits most. But it might make sense for some people, like those with prediabetes, PCOS, metabolic syndrome, or even older adults looking to support healthy aging.  As always, it’s something to talk through with your healthcare provider.  The science is exciting, but it’s all about finding what makes sense for you. Thank you for listening to The Peptide Podcast. If you enjoyed the show and want to support what we do, head over to our <a href="https://pepties.com/partners/">Partners Page</a>. You'll find some amazing brands we trust—and by checking them out, you're helping us keep the podcast going.  Until next time, be well, and as always, have a happy, healthy week.

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Beyond Blood Sugar: Metformin’s Surprising Promise

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