The prescription drugs rich longevity seekers take off label, what the trials show, what they cost, and why one famous user quit.
This in-depth guide covers everything you need to know about rapamycin longevity, metformin and glp-1s: the evidence. Based on verified income data and real-world case studies from our database of 138 side hustle tactics.
Rapamycin for longevity rests on strong mouse data and thin human data: one year-long human trial, PEARL, found it fairly safe at low weekly doses but missed its main goal. Metformin's big aging trial, TAME, has spent years trying to raise its budget, and GLP-1 drugs like Wegovy have hard heart data in people with heart disease and overweight or obesity, and no proof of slower aging in anyone else. All three are prescription drugs with real side effects, so the honest starting point is a doctor's office, and the cheapest version of what they promise is mostly exercise, sleep and a waistline you watch.
That is the short answer. The longer one is more interesting, because the people with the most money and the best doctors have tried these drugs in public, and some of them quit.
Why rich people reach for prescription drugs at all
Picture the problem from their side. You already sleep well, train with a coach, eat food a chef plans around your blood work, and see a physician on call. The free and cheap levers are pulled. What is left are drugs that worked in mice and a few small human studies, available off label from a willing doctor.
Off label means a doctor prescribes a drug the FDA approved for one condition (organ transplant, diabetes, obesity) for a different purpose (slowing aging). It is legal. It also means nobody has shown the drug does that job in people, and the dose is a guess.
So the question for you is a fair one: when people with unlimited budgets still disagree about these drugs, what should someone on a normal income take from that?
This post covers the three drugs that come up most: rapamycin, metformin and GLP-1s, plus a short note on acarbose. Supplements such as NMN live in our NMN and NAD+ evidence review, and the wider list of what the very rich swallow each morning has its own roundup in this series.
A plain note before you read further: this is general information for adults, and a doctor who knows your history is the right person to advise you. Every drug here can interact with other medicines and cause harm. If any of it interests you, talk to your doctor, and never start a prescription drug from a blog post, a podcast or a telehealth questionnaire alone.
Rapamycin: the mouse result that started it all
Rapamycin (generic name sirolimus) is an immunosuppressant. Doctors give it to kidney transplant patients so their bodies do not reject the new organ. It works by blocking a growth signal inside cells called mTOR.
The longevity story began in 2009. The National Institute on Aging's Interventions Testing Program fed rapamycin to genetically mixed mice starting at 600 days of age, which is roughly late middle age for a mouse. The paper in Nature reported that it extended lifespan in both sexes, with a 14% increase for females and 9% for males measured at the age when 90% had died. The effect showed up at three separate labs, which is why researchers took it seriously.
Mice are a long way from people, though. How many mouse results can you think of that turned into human cures?
What human trials show so far
The best human data on rapamycin for healthy aging is small.
- PEARL (2025). A 48-week, double-blind, placebo-controlled trial gave healthy adults aged 50 to 85 placebo, 5 mg or 10 mg of compounded rapamycin once a week. 114 participants completed it. The main measure, visceral fat, did not change significantly. Adverse events were similar across groups. Women on 10 mg gained lean tissue and reported less pain, and the 5 mg group reported better emotional well-being and general health. The authors concluded the regimen was "relatively safe" over 48 weeks. The paper also notes that compounded rapamycin turned out to reach about one third the blood level of the commercial tablets, so the real doses were lower than the labels on the bottles. One more detail matters: the paper lists the authors as employees and shareholders of AgelessRx, a telehealth company that prescribes rapamycin.
- Immune function (2018). In a Novartis-backed phase 2a trial of 264 older adults, six weeks of a low-dose combination of two related mTOR inhibitors was linked to fewer reported infections over the following year and a better response to flu vaccine. That study used different drugs (everolimus plus BEZ235), so it tells you about the pathway more than about rapamycin pills.
- Dogs, still running. The Dog Aging Project's TRIAD trial is testing whether rapamycin extends lifespan in healthy middle-aged pet dogs. The design paper calls it the first rigorous test of a drug against biological aging, with lifespan as an endpoint, outside a lab in any species. Results are years away.
Put together: rapamycin at low weekly doses looks tolerable for about a year in healthy people, and nobody has shown it makes humans live longer or age slower.
Who has said they take it, and who stopped
The most detailed public account comes from Bryan Johnson, whose whole routine is covered in our Blueprint protocol breakdown. On November 14, 2024, he posted on X that he had stopped rapamycin on September 28 after "almost 5 years of experimentation." He listed the schedules he tried: weekly 5, 6 and 10 mg, biweekly 13 mg, and alternating 6 and 13 mg. Those are his reported doses, shared here as reporting and never as a suggestion.
His reason, in his own words: "the benefits of lifelong dosing of Rapamycin do not justify the hefty side-effects (intermittent skin/soft tissue infections, lipid abnormalities, glucose elevations, and increased resting heart rate)." He added that "dosage adjustments had no effect." That is one person's experience with a full medical team watching his blood, so treat it as a case report. It still lines up with what the drug label warns about.
Peter Attia, the physician whose framework is covered in our Attia protocol post, has discussed rapamycin many times on his podcast. In the notes for his 300th episode (May 2024) his team wrote that he "puts rapamycin in the promising category, but clearly it's not proven." CBS News reported in October 2025 that mouth sores, a known side effect, led him to pause it.
Would you take a drug that the most committed self-experimenter in the world dropped after five years?
The risks, from the label itself
The FDA label for sirolimus carries a boxed warning, the agency's strongest, for "increased susceptibility to infection and the possible development of lymphoma and other malignancies" from immunosuppression. That warning was written for transplant patients, who take it once daily alongside other immune drugs, a different situation from a weekly longevity schedule. The label also lists high triglycerides and cholesterol, impaired wound healing, fluid build-up, mouth sores (stomatitis) and declining kidney function. It warns that grapefruit juice "must not be taken with" sirolimus because it slows how the body clears the drug, and it flags interactions with common antibiotics and antifungals such as clarithromycin and itraconazole.
That interaction list is one of the quieter dangers. A doctor who prescribes rapamycin for aging needs to know every other drug you take, including a short course of antibiotics from an urgent care clinic.
Metformin is the first-line drug for type 2 diabetes, it has been around for decades, and it costs very little. Its longevity reputation comes from three places.
- A widely cited UK study. In 2014, researchers using UK health records reported that people with type 2 diabetes who started on metformin lived longer than matched people without diabetes. That headline launched a thousand podcast segments.
- A Danish study that disagreed. In 2022, a study of Danish national registers, including twin pairs, found that people starting metformin for diabetes had higher mortality than people without diabetes, even after adjusting for other illnesses. The authors said their different result was unlikely to come from method choices.
- Mice. In the same NIA testing program that made rapamycin famous, metformin alone did not significantly extend lifespan at the dose tested. Metformin combined with rapamycin did extend it.
So the observational evidence points both ways, and the best mouse test came back flat.
MILES and the exercise problem
MILES, the Metformin in Longevity Study at Albert Einstein College of Medicine, was a small crossover trial. The Einstein team's paper on 14 participants around age 70 gave each person six weeks of metformin and six weeks of placebo, then took muscle and fat biopsies. Metformin changed the activity of hundreds of genes in muscle and fat, including pathways linked to aging. That is a biological signal in a tiny group, measured over weeks.
Two other trials raised a concern that matters more for most readers. In older adults doing 12 weeks of aerobic training, metformin blunted the gains in insulin sensitivity and VO2 max that exercise produced, and it cancelled the exercise-driven rise in muscle mitochondrial function. In the MASTERS trial, healthy people 65 and older doing 14 weeks of strength training gained less lean mass and thigh muscle on metformin than on placebo.
Exercise is the best-supported longevity habit there is. If a pill might take some of its benefit away, which one would you keep?
Attia has talked about this shift. His notes for a 2020 episode say he had been taking metformin for about seven years, and quote him: "I don't view it really as a pro longevity agent yet."
Where TAME stands
TAME (Targeting Aging with Metformin) is the trial designed to settle this. Nir Barzilai of Albert Einstein College of Medicine and colleagues laid out the plan in Cell Metabolism in 2016. The idea was clever: use metformin to show regulators that aging itself can be a target for a drug.
NPR reported in April 2024 that the goal is to enroll 3,000 people aged 65 to 79 for six years, and that funding has been slow. Barzilai told NPR: "The main obstacle with funding this study is that metformin is a generic drug, so no pharmaceutical company is standing to make money." I found no primary announcement from the trial team since then saying enrollment has begun, so treat TAME as unfinished.
There is a money lesson tucked in there. A cheap, off-patent drug can sit untested for a decade because nobody can profit from proving it works. Where do you think that leaves the claims you hear about it online?
The metformin label carries a boxed warning for lactic acidosis, a rare but sometimes fatal build-up of acid in the blood. Listed risk factors include kidney problems, age 65 or older, heavy drinking, contrast dye scans and surgery. The label also says "metformin may lower vitamin B12 levels" and advises checking B12 every two to three years. Stomach upset is common when people start it.
GLP-1 drugs: what Musk actually said
GLP-1 drugs (semaglutide, sold as Wegovy and Ozempic, and tirzepatide, sold as Zepbound and Mounjaro) are the newest entry on the longevity menu. They are approved for diabetes and for weight management. Their link to "longevity" comes mostly from what they do to weight and heart risk.
Elon Musk is the name most people connect with them, so here is the record from his own posts:
- October 1, 2022. Asked how he looked so fit, he replied "Fasting". Hours later he added "And Wegovy".
- November 16, 2022. Asked what had made the most difference, he wrote: "Fasting + Ozempic/Wegovy + no tasty food near me."
- December 11, 2024. He posted that "Nothing would do more to improve the health, lifespan and quality of life for Americans than making GLP inhibitors super low cost to the public."
- December 26, 2024. He posted a photo captioned "Ozempic Santa", and Fortune reported his follow-up: "Technically, Mounjaro, but that doesn't have the same ring to it."
Notice what those posts describe. The personal ones are about losing weight, and the 2022 replies pair the drug with fasting and keeping tempting food out of reach. The lifespan post is about Americans in general. None of them says the drug slowed his own aging.
The evidence for GLP-1s and long life
The strongest data comes from SELECT, a trial of 17,604 adults aged 45 or older with existing heart disease, a BMI of 27 or more and no diabetes. Over a mean follow-up of 39.8 months, weekly semaglutide 2.4 mg cut the combined rate of cardiovascular death, heart attack and stroke from 8.0% to 6.5% (a hazard ratio of 0.80). That is a real, large benefit for that group. The same trial reported that 16.6% of people on semaglutide stopped the drug because of side effects, twice the placebo rate.
For a lean, healthy person who wants to age slower, no trial shows a benefit. That gap is the whole debate. Are you in the group the trial studied, or would you be extrapolating?
GLP-1 risks
The Wegovy label has a boxed warning about thyroid C-cell tumors seen in rodents, and it is off limits for anyone with a personal or family history of medullary thyroid cancer or MEN 2. It also lists acute pancreatitis, gallbladder disease, low blood sugar, kidney injury, a faster heart rate, and suicidal thoughts as risks to watch, with nausea, diarrhea, vomiting and constipation as the most common side effects.
The FDA has also warned about compounded and unapproved GLP-1 drugs. It reports dosing errors with compounded injectable semaglutide, "some requiring hospitalization," counterfeit Ozempic in the US supply, and products sold online "for research purposes." If you have read our BPC-157 guide or our peptide market analysis, the pattern will look familiar: a gray market grows wherever demand outruns prescriptions.
Acarbose: the quiet one
Acarbose is an older diabetes drug that slows how fast you absorb starch and sugar. In the NIA mouse program it raised median lifespan 22% in males and 5% in females, and a later round confirmed the male benefit even when treatment started at 16 months. There are no human aging trials. The label reports flatulence in 74% of patients in US placebo-controlled trials, against 29% on placebo, along with diarrhea and abdominal pain. The label adds that the gas tends to ease over time.
What it costs per month, as of 2026
Here is what the drugs themselves cost a cash-paying American, as of 2026. Doctor visits and lab tests come on top, and they usually cost more than the pills.
| Drug | Approved for | Longevity evidence in humans | Cash price per month (as of 2026) | Biggest risks |
|---|
| Rapamycin (sirolimus) | Kidney transplant rejection | One 48-week safety trial (PEARL); no lifespan data | Generic 1 mg, 30 tablets: about $35 to $40 with a discount card at CVS or Walgreens, $494 retail. Telehealth plans start at $65 a month at AgelessRx | Infections, high lipids and glucose, mouth sores, grapefruit and antibiotic interactions |
| Metformin | Type 2 diabetes | Mixed observational data; TAME not complete | 500 mg, 60 tablets: about $5 to $15 with a discount card | Lactic acidosis (rare), low B12, stomach upset, blunted exercise gains |
| Semaglutide (Wegovy) | Weight management, heart risk in people with heart disease and overweight or obesity | Heart benefit in people with heart disease and overweight or obesity (SELECT) | Pen: $349 a month self-pay through NovoCare after an intro offer; pill doses from $149 to $299 | Nausea, pancreatitis, gallbladder disease, thyroid tumor warning, counterfeits |
| Acarbose | Type 2 diabetes | Mice only | 25 mg, 90 tablets: about $25 to $35 with a discount card at large chains | Gas, diarrhea, abdominal pain |
Discount-card prices are estimates that change by pharmacy. Your insurer will almost never cover a drug prescribed for aging, so assume cash.
For the very rich, the pill is the cheap part. The expense is the physician who prescribes it, orders blood work every few months and adjusts the plan, which is what a longevity clinic or concierge practice sells. We priced those in our longevity clinic cost breakdown.
Longevity drug claims that outrun the data
Some claims you will hear about these drugs go well past the data:
- "Rapamycin is proven to extend human life." It has been shown to extend mouse lifespan. In people, the longest trial ran 48 weeks and missed its main target.
- "Metformin makes people without diabetes outlive everyone." That rests on one observational study, and a later Danish study found the opposite.
- "GLP-1s are anti-aging drugs." They cut heart events in a specific high-risk group. Nobody has tested them for aging in healthy, lean people.
- "More is better." Johnson said his side effects persisted through several dose changes.
- Buying "research" peptides or compounded injections online. The FDA's warnings on dosing errors and counterfeits apply directly.
- Stacking several of these at once without a doctor tracking labs. Interactions, low blood sugar and infection risk add up, and you would have no way to tell which drug caused what.
What the drugs aim for, done without a prescription
Here is the uncomfortable, useful part. The things these drugs aim to do (better insulin sensitivity, lower visceral fat, less heart risk, more muscle in old age) are the things exercise, sleep and diet already do, and the metformin trials suggest the pill can even get in the way of the workout.
What does a normal-budget version look like?
- Train for muscle and fitness. Two or three strength sessions a week plus regular cardio. Bodyweight training and walking at home cost nothing.
- Get the blood work these doctors start with. A primary care visit with a fasting glucose, HbA1c, lipid panel and kidney function check may be covered by your insurance as part of a yearly physical. Ask what your plan includes before you pay for a private panel.
- Watch your waist. Visceral fat was PEARL's main target. A cloth tape measure around your waist tracks the same idea roughly.
- Ask your doctor directly. If you have prediabetes, obesity or heart disease, metformin or a GLP-1 may be a legitimate treatment for that condition. That conversation belongs to you and your physician, based on your own numbers.
If you ever find yourself pricing these drugs, also price the doctor who will monitor you. Pills plus regular visits and labs add up to a real line in your budget. It is worth knowing how much money is enough for the things that matter to you before you spend on the speculative ones, and building the income that pays for good care is the goal this site exists to help with. Money you would have spent on a speculative pill can go into plain index funds instead, where the long-run evidence is far stronger.
Your three steps this week
Pick three things to do before next Sunday:
- Book your yearly physical, or check when your last one was, and ask for HbA1c and a lipid panel.
- Do two strength sessions and one longer walk or ride. Write down what you lifted.
- Measure your waist at the belly button and write the number down to compare in three months.
If you are curious about rapamycin, metformin or a GLP-1, bring three questions to that appointment: whether your own blood work gives a medical reason to take it, what you would measure to see if it helps or hurts, and what it interacts with.
Which of those three steps could you do today?