Best Meds for Longevity: A Realistic Guide to What the Evidence Actually Supports

The longevity field has a noise problem. Scroll through social media and you'll find influencers stacking a dozen supplements, promoting peptides with no human data, and treating every new molecule like the fountain of youth. Meanwhile, a small number of medications have been quietly building decades of real evidence — the kind that comes from clinical trials, epidemiological studies, and the prescribing practices of serious longevity physicians.

This guide focuses on what actually holds up. These are the medications most commonly discussed and prescribed in evidence-based longevity medicine, along with an honest look at what we know, what we don't, and what the trade-offs are.

Important note: This article is for educational purposes only. None of this is medical advice. Every medication listed here carries risks, requires medical supervision, and should only be used under the guidance of a licensed physician.

Longevity Medication Comparison Table

1. Metformin — The Workhorse

If there's a single medication that longevity physicians talk about more than any other, it's metformin. Originally developed for type 2 diabetes, metformin has been used safely in humans for over 60 years, making it one of the most well-studied drugs on the planet.

The longevity interest started with a striking observation: diabetic patients taking metformin appeared to live longer than non-diabetic controls who weren't taking it. That finding, published in a large UK study, launched a wave of research into metformin's potential anti-aging effects beyond glucose control.

The proposed mechanisms are compelling. Metformin activates AMPK, a key cellular energy sensor that promotes efficient metabolism. It reduces chronic inflammation, improves insulin sensitivity, and may lower the risk of several age-related cancers. The TAME trial (Targeting Aging with Metformin) is the first FDA-approved clinical trial specifically designed to test whether a drug can slow aging itself — and metformin is the drug being tested.

The trade-offs are real but manageable. GI side effects like nausea and diarrhea are common early on, though they usually resolve. There's also an ongoing debate about whether metformin blunts some of the benefits of exercise, particularly muscle hypertrophy. For this reason, some longevity physicians cycle metformin around training days.

Who it's for: Adults concerned about metabolic health, insulin resistance, or cancer risk, particularly those who are not elite athletes.

Typical longevity dose: 500mg–1,500mg daily (extended release preferred for GI tolerance)

2. Rapamycin — The Most Exciting and Most Debated

Rapamycin is the medication that gets longevity researchers most animated. It's an mTOR inhibitor originally used as an immunosuppressant for organ transplant patients. In animal studies, rapamycin has extended lifespan more consistently and across more species than any other compound tested — including mice, even when started late in life.

The mechanism centers on mTOR, a master regulator of cell growth. When mTOR is constantly active (as it tends to be with modern diets high in protein and calories), cells prioritize growth over maintenance. Rapamycin dials that down, promoting autophagy — the cellular cleanup process that clears damaged proteins and dysfunctional components. Think of it as shifting your cells from "build" mode to "repair" mode.

A growing number of longevity physicians prescribe low-dose rapamycin on a weekly or biweekly schedule, a very different protocol than the daily high doses used in transplant medicine. At these lower doses, early human data suggests it may actually enhance immune function rather than suppress it. A notable study showed that low-dose rapamycin improved elderly patients' response to the flu vaccine — the opposite of what you'd expect from an "immunosuppressant."

The honest caveat: we do not yet have large, long-term human trials proving rapamycin extends lifespan in healthy people. The animal data is remarkable, the mechanistic logic is sound, and early human studies are encouraging, but certainty is premature.

Who it's for: People working with a longevity-focused physician who are comfortable being on the earlier end of clinical adoption.

Typical longevity dose: 3mg–6mg once weekly (protocols vary)

3. GLP-1 Receptor Agonists — Beyond Weight Loss

Semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound) have dominated headlines as weight loss drugs. But the longevity implications run much deeper than the number on a scale.

The SELECT trial demonstrated that semaglutide reduced major adverse cardiovascular events by 20% in overweight and obese adults — independent of whether they had diabetes. Subsequent data has shown reduced risk of kidney disease progression, heart failure, and even hints at lower rates of certain cancers and neurodegenerative conditions. The mechanisms appear to involve reduced systemic inflammation, improved endothelial function, and better metabolic regulation across multiple organ systems.

For longevity, the significance is hard to overstate. Excess body fat, particularly visceral fat, is one of the strongest drivers of chronic disease and accelerated aging. GLP-1 agonists address this more effectively than any previous pharmaceutical intervention, and they appear to deliver cardiovascular and metabolic benefits that go beyond what weight loss alone would predict.

The trade-offs include GI side effects (nausea, especially early on), cost, and concerns about lean muscle mass loss during rapid weight reduction. Longevity-minded physicians typically combine GLP-1 therapy with resistance training and adequate protein intake to preserve muscle — which is itself a critical longevity factor.

Who it's for: Individuals with excess body fat and elevated cardiometabolic risk who haven't achieved results through lifestyle alone.

Typical dose: Semaglutide 0.25mg–2.4mg weekly (titrated up); tirzepatide 2.5mg–15mg weekly

4. Testosterone Replacement Therapy (TRT)

Testosterone declines roughly 1–2% per year in men starting around age 30. By the time a man reaches his 50s or 60s, levels may be significantly below what's needed to maintain muscle mass, bone density, cognitive function, metabolic health, and quality of life.

The longevity case for TRT is nuanced. Adequate testosterone supports several pillars of healthspan: it helps preserve lean muscle (the single strongest predictor of functional independence in aging), maintains bone mineral density, improves insulin sensitivity, and supports cardiovascular health when levels are in the physiologic range.

The TRAVERSE trial, the largest randomized controlled trial of TRT in older men, found no increased risk of major cardiovascular events, addressing one of the longstanding safety concerns. Prostate cancer risk, another common worry, has not been shown to increase with physiologic testosterone replacement in men without pre-existing prostate cancer.

The key word is physiologic. Longevity-focused TRT aims to restore levels to a healthy mid-range, not to push testosterone to supraphysiologic levels. The goal is optimization, not maximization.

Who it's for: Men with clinically low or declining testosterone confirmed by lab work, who are experiencing symptoms like fatigue, muscle loss, poor sleep, or metabolic decline.

Typical approach: Testosterone cypionate injections, topical gels, or pellets — dosed to achieve levels of 600–900 ng/dL

5. Statins — The Unsexy Essential

Statins aren't exciting. They don't have a biohacking brand ambassador. But the evidence base for cardiovascular risk reduction is arguably the strongest of any medication on this list.

Cardiovascular disease remains the number one killer globally. Elevated ApoB-containing lipoproteins (primarily LDL) drive atherosclerotic plaque formation over decades. Statins reduce LDL effectively and have been shown across dozens of large randomized trials to significantly reduce heart attacks, strokes, and cardiovascular death.

Peter Attia, who has shaped much of modern longevity thinking, has described early and aggressive lipid management as one of the highest-leverage interventions for extending lifespan. His argument: the longer your arteries are exposed to elevated ApoB, the greater your cumulative risk. Starting earlier — not waiting until you've already had an event — dramatically changes the math.

Side effects like muscle aches are reported by some users, though large blinded studies suggest the actual rate of statin-caused muscle symptoms is much lower than commonly believed. For those who can't tolerate statins, alternatives like PCSK9 inhibitors or bempedoic acid exist.

Who it's for: Anyone with elevated ApoB or LDL who wants to reduce lifetime cardiovascular risk, especially those with a family history.

Typical options: Rosuvastatin 5–20mg or atorvastatin 10–40mg daily

6. Acarbose — The Sleeper Pick

Acarbose rarely makes headlines, but it has a quietly compelling longevity profile. It works by slowing carbohydrate digestion, blunting post-meal glucose spikes — the kind of repeated metabolic stress that contributes to insulin resistance over time.

In the Interventions Testing Program (ITP), one of the most rigorous animal lifespan studies ever conducted, acarbose extended lifespan in male mice significantly. Human data shows it effectively reduces glucose variability and may lower the risk of cardiovascular events in people with impaired glucose tolerance.

For longevity-focused individuals who want to manage post-meal glucose without metformin (or in addition to it), acarbose is a practical tool. Side effects are primarily GI — gas and bloating from undigested carbohydrates reaching the lower gut — which tend to improve as the body adapts.

Who it's for: People focused on glucose optimization, particularly those with elevated post-meal glucose spikes identified via CGM.

Typical longevity dose: 25mg–50mg before carbohydrate-heavy meals

7. NAD+ Precursors (NMN / NR) — Promising but Early

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme essential to cellular energy production, DNA repair, and sirtuin activation. NAD+ levels decline significantly with age, and restoring them has become one of the central hypotheses in aging research.

NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are precursors that the body converts into NAD+. Animal studies have shown improvements in metabolic function, endurance, and markers of aging. David Sinclair has been one of the most vocal proponents, citing NAD+ restoration as a key component of his personal longevity protocol.

The honest assessment: human data is still limited. Some trials have shown increases in blood NAD+ levels, but whether that translates to meaningful clinical outcomes like reduced disease or extended lifespan remains unproven. These compounds are currently sold as supplements, not medications, which means less regulatory oversight and variable product quality.

Who it's for: People willing to invest in an emerging intervention with strong theoretical backing but incomplete human evidence.

Typical dose: NMN 250mg–1,000mg daily; NR 300mg–600mg daily

How to Think About a Longevity Medication Stack

The physicians doing this work at the highest level don't prescribe one medication in isolation. They build protocols around an individual's lab work, health history, risk factors, and goals. A typical longevity-focused patient might be on metformin for metabolic health, a statin for cardiovascular protection, and TRT if labs show deficiency — with periodic CGM monitoring and quarterly blood panels to track progress.

The common thread: every intervention is data-driven, monitored, and adjusted. This isn't about taking pills and hoping for the best. It's about using pharmaceutical tools alongside lifestyle optimization — sleep, nutrition, exercise, stress management — to systematically reduce the drivers of aging.

The Bottom Line

The medications with the strongest longevity evidence today are, frankly, the least glamorous ones: metformin, statins, and now GLP-1 agonists. Rapamycin is the most intellectually exciting but still needs more human data. TRT is highly effective for the right candidate. And NAD+ precursors remain a compelling bet that hasn't fully paid off yet.

The best longevity protocol isn't the one with the most medications. It's the one built on solid diagnostics, monitored by a physician who understands the science, and paired with the lifestyle foundations that no pill can replace.