GLP-1, Metformin & Rapamycin: a primer
A fact-based review of three treatments that may (or may not) help you age slower.
GLP-1, Metformin and rapamycin: three names that keep cropping up in the modern longevity conversation. Below is a brief but detailed breakdown of each of these three…things (they’re not “drugs” and I’m not sure there’s a single word that accurately comprises all three). Here’s a bulleted introduction to each thing, and below I get into what they do, the necessary cautions and the bottom line for each:
Disclosure: I used AI tools to research the information below, checking sources and facts for accuracy. Oh, and in case you missed it:
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GLP-1: An emergent wonder anti-aging and longevity drug?
Glucagon-like peptide-1, or GLP-1, is a hormone your body naturally produces, mainly in your gut, in response to eating. Its main job is to help regulate blood sugar by prompting your pancreas to release insulin (which lowers blood sugar) and by reducing the release of glucagon (which raises blood sugar). GLP-1 also slows down how quickly your stomach empties, which helps you feel full longer and can reduce how much you eat.
GLP-1 and aging: How does it affect longevity?
Recent research indicates GLP-1’s influence goes far beyond blood sugar and appetite control. Scientists are now exploring how GLP-1 and drugs that mimic its action (called GLP-1 receptor agonists) might help slow down aging and extend healthy lifespan.
Here’s what’s emerging:
Cellular protection: GLP-1 appears to protect cells from damage caused by oxidative stress and chronic inflammation—two key drivers of aging and age-related diseases.
Molecular rejuvenation: In animal studies, GLP-1 drugs have reversed many age-related changes at the molecular level, including improving the function of genes and proteins involved in cell repair, energy production, and metabolism. These effects were especially noticeable in older animals, not young ones, and occurred even without significant weight loss.
Brain and body benefits: GLP-1 may help protect the brain from age-related decline, improve memory, and reduce the risk of diseases like Alzheimer’s. It also seems to benefit the heart, kidneys, and bones, all of which are vulnerable as we age.
Potential for longer healthspan: Because GLP-1 drugs can reduce risk factors for chronic diseases (like diabetes, heart disease, and possibly neurodegenerative diseases), they could help people stay healthier for longer as they age.
How does GLP-1 work?
GLP-1’s anti-aging effects are thought to come from its ability to:
Boost the body’s natural repair mechanisms (like DNA repair)
Improve how cells handle stress
Reduce harmful inflammation
Support healthy metabolism and energy production in cells
What’s the evidence?
Animal studies show promising results for reversing signs of aging at the molecular and functional levels.
Human studies are ongoing, but early evidence suggests GLP-1 drugs can help manage or prevent several age-related diseases, potentially expanding healthy lifespan.
GLP-1 risks
While GLP-1 drugs are generally safe, especially for people with diabetes or obesity, they can cause side effects like nausea or, in some cases, loss of muscle mass, which is a concern for older adults.
The bottom line re GLP-1s
GLP-1 is a hormone that helps control blood sugar and appetite and is now being studied for its potential to slow aging and extend healthy years of life. By protecting cells, reducing inflammation and improving metabolism, GLP-1 and its related drugs may offer new ways to combat age-related decline and diseases.
Metformin: A diabetes drug with anti-aging potential
Metformin is a widely prescribed medication for type-2 diabetes, first synthesized in 1922 and FDA-approved in 1994 (72 years later!). Derived from the French lilac plant, Metformin is known for lowering blood sugar by reducing glucose production in the liver and improving insulin sensitivity. Recently, scientists have explored its potential to slow aging and extend healthy lifespan.
But fair warning: Bozos like David Sinclair, who has repeatedly been called out by his peers for overstating if not fabricating clinical results of longevity research, are also behind glossy, overly optimistic reviews of Metformin, like this one.
How Metformin Works
Blood sugar control: Blocks liver glucose production and helps muscles absorb sugar more efficiently.
Activates AMPK: A cellular “energy sensor” that improves metabolism and reduces oxidative stress.
Anti-inflammatory effects: Lowers chronic inflammation linked to aging and diseases like heart disease and Alzheimer’s.
Metformin & longevity
Healthspan: Strong evidence shows metformin extends years of healthy life by delaying age-related diseases:
Reduces cardiovascular disease risk by improving blood vessel health.
Lowers cancer risk in diabetics and may protect against cognitive decline.
A 2024 study in monkeys found metformin reversed molecular aging markers (e.g., reduced inflammation, improved DNA repair) in multiple organs, effectively making their tissues 6 years “younger.”
Lifespan: The evidence is mixed:
In mice, metformin extended lifespan by 14% when started young, but had minimal effects in older mice, a 2013 study found.
Human data from diabetics suggest longer lifespans compared to non-diabetics, but it’s unclear if this applies to healthy people.
Metformin controversies and risks
Does it work for healthy people?
Benefits may depend on existing metabolic issues. Studies in disease-free individuals show inconsistent results.
Critics argue its anti-aging effects are indirect, stemming from better blood sugar control rather than directly targeting aging pathways.
Side effects
Common: Nausea, diarrhea, and stomach pain (especially when starting the drug).
Vitamin B12 deficiency: Long-term use can lower B12 levels, raising anemia and nerve damage risk.
Age-dependent effectiveness
In mice, metformin’s benefits diminished when given later in life. Which raises questions about its utility for older adults.
Dose matters
High doses (1% of diet) were toxic in mice, while low doses (0.1%) extended healthspan. Human dosing strategies are still being refined.
The bottom line re Metformin
Metformin shows promise for extending healthspan by preventing diseases like diabetes, heart disease, and dementia. But its ability to increase lifespan, especially in healthy individuals, remains uncertain. It’s generally safe for diabetics but its side effects and variable effectiveness in non-diabetics mean proceed with caution.
Rapamycin: Wonder drug found in Easter Island dirt?
Rapamycin (also called sirolimus) is a natural compound discovered in 1964 (the baby boomer of longevity wonder drugs) in soil from Easter Island (aka Rapa Nui). Originally used to prevent organ transplant rejection and treat cancer, it’s now being studied for its surprising potential to slow aging.
What Rapamycin does
Targets mTOR: Rapamycin blocks a protein complex called mTOR, which acts like a control center for cell growth, metabolism and aging. By slowing mTOR, rapamycin helps cells focus on repair and survival instead of growth.
Extends lifespan: In animals, rapamycin increases lifespan by 10% to 15%, even when given later in life. It delays age-related diseases like cancer, Alzheimer’s and heart disease by reducing inflammation and clearing damaged “zombie cells.”
Animal studies: Mice given rapamycin live longer and stay healthier, with stronger hearts, better immune function, and fewer tumors. But mice aren’t people….
Human potential: Early trials suggest it may improve immune health in older adults and treat age-related conditions like gum disease.
Rapamycin controversies and risks
Immune suppression: At high doses (used in transplants), rapamycin weakens immunity, raising infection risks. However, low “anti-aging” doses may modulate immunity — calming overactive responses while preserving defenses. Critics argue even low doses could increase infection susceptibility in vulnerable people.
Metabolic side effects: Can raise cholesterol and blood sugar, potentially worsening heart disease risk if unmanaged.
Long-term safety: No long-term human data exist for anti-aging use. Critics question using it without proven benefits in healthy people.
Current Rapamycin research (2024–2025)
Human trials: Testing rapamycin for age-related muscle loss, immune decline, and Alzheimer’s.
Combination therapies: Pairing rapamycin with exercise or other drugs to maximize benefits and minimize risks.
Senolytics: Newer anti-aging drugs that clear zombie cells are being compared to rapamycin for effectiveness.
Should you consider Rapamycin?
For healthy adults: Experts are split. Some take low doses off-label, citing animal data and small human studies. Others, like U.C. Berkeley’s Dr. Andrew Dillin, quoted in this New York Times article on rapamycin, thinks not: “Why take risks with unproven benefits?” he told The Times. “I’ll pass.”
For older adults: May help reverse immune aging, but requires close monitoring for infections and metabolic changes.
The bottom line re Rapamycin
Rapamycin is a promising but controversial anti-aging candidate. While it shows remarkable potential in animals, human risks and benefits remain uncertain. Current trials will determine if it’s a true longevity breakthrough or a risky gamble.
Whew! That was a lot of information. I hope it’s helpful to you.
I wonder if one could take Rapamycin if already on a GLP-1 Medication.
Nice review and summary. Thanks!