Longevity Pharmacology: The Complete Drug Review
Beyond lifestyle, a handful of drugs are studied or used with longevity in mind. This review covers the main ones, what their trials actually measured, and where the evidence stops: GLP-1 receptor agonists, SGLT2 inhibitors, metformin, aspirin, rapamycin and acarbose.
- No drug has yet been shown in a randomized trial to extend healthy human lifespan. Several lower heart attacks, strokes, heart failure or deaths in specific patient groups, which is valuable but not the same thing.
- In the SELECT trial, weekly semaglutide 2.4 mg lowered major cardiovascular events by 20% in people with heart disease and overweight or obesity but no diabetes.2
- In people with type 2 diabetes at high cardiovascular risk, empagliflozin lowered hospitalization for heart failure by 35% and death from any cause by 32%.6
- Rapamycin extended median and maximal lifespan in mice even when started at 600 days of age;7 in people, a 48-week trial found low-dose intermittent use relatively safe, with improvements in lean mass and pain in women.8
- Acarbose, a diabetes drug, increased median lifespan by 22% in male mice and 5% in females; it has not been tested for longevity in people.5
The picture is both more developed and more limited than popular discussion suggests. Several drugs have strong outcome data for specific diseases, but none has been shown to extend healthy human lifespan. Many candidates target processes counted among the hallmarks of aging, such as deregulated nutrient sensing.1
Tier 1: Cardiovascular Outcome Trials in People
GLP-1 receptor agonists: SELECT enrolled 17,604 adults aged 45 or older with existing cardiovascular disease and overweight or obesity but no diabetes. Over the trial, cardiovascular death, heart attack or stroke occurred in 6.5% of those on weekly semaglutide 2.4 mg and 8.0% on placebo, a 20% lower risk.2
SGLT2 inhibitors: In EMPA-REG OUTCOME, 7,020 people with type 2 diabetes at high cardiovascular risk were treated for a median of 3.1 years. Hospitalization for heart failure fell from 4.1% to 2.7% (a 35% relative reduction) and death from any cause from 8.3% to 5.7% (32%).6 These results apply to people with diabetes and heart disease, not to healthy adults.
Tier 2: Human Data, No Longevity Trial Results
Metformin: The TAME trial was designed to test metformin against aging.3 One caution for people who exercise: in a 12-week trial in older adults, metformin blunted the gains in insulin sensitivity and VO2 max from aerobic training.9
Low-dose aspirin: In ASPREE, 19,114 healthy older adults took aspirin or placebo. Death from any cause, a secondary outcome, was 12.7 per 1,000 person-years on aspirin against 11.1 on placebo, with cancer the major contributor.4 The US Preventive Services Task Force recommends against starting low-dose aspirin for primary prevention at 60 or older.10
Tier 3: Strong Animal Data, Limited Human Longevity Evidence
Rapamycin: In genetically diverse mice, rapamycin started at 600 days of age extended median and maximal lifespan in both sexes.7 In people, the 48-week PEARL trial found low-dose intermittent rapamycin relatively safe in healthy adults, with improvements in lean tissue mass and pain in women.8 It is a prescription immunosuppressant, and we do not give doses.
Acarbose: a diabetes drug that slows carbohydrate digestion. In the Interventions Testing Program, it increased median lifespan by 22% in male mice and 5% in females, and maximum lifespan by 11% and 9%.5 It has not been tested for longevity in people.
Evidence Summary Table
| Drug | Animal Longevity Data | Human CV Outcomes | Human Longevity RCT | Off-Label Longevity Use |
|---|---|---|---|---|
| GLP-1 agonists | Moderate | Strong (SELECT, LEADER) | None | Increasing |
| SGLT2 inhibitors | Moderate | Strong (EMPEROR, DAPA) | None | Increasing |
| Metformin | Mixed | Observational only | TAME pending | Widespread |
| Rapamycin | Very strong (ITP) | None | None | Growing |
| Acarbose | Strong (ITP male) | None longevity-specific | None | Minimal |
| Aspirin (primary prev.) | Limited | Negative (ASPREE) | Not recommended | Now discouraged |
Put this research into practice: Supplement Evidence Database · Supplement Interaction Checker
References
- 1López-Otín C, et al. "Hallmarks of aging: An expanding universe." Cell. 2023;186(2):243-278. PubMed · DOI
- 2Lincoff AM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes." N Engl J Med. 2023;389(24):2221-2232. PubMed · DOI
- 3Barzilai N, et al. "Metformin as a Tool to Target Aging." Cell Metab. 2016;23(6):1060-1065. PubMed · DOI
- 4McNeil JJ, et al. "Effect of Aspirin on All-Cause Mortality in the Healthy Elderly." N Engl J Med. 2018;379(16):1519-1528. PubMed · DOI
- 5Harrison DE, et al. "Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males." Aging Cell. 2014;13(2):273-82. PubMed · DOI
- 6Zinman B, et al. "Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes." N Engl J Med. 2015;373(22):2117-28. PubMed · DOI
- 7Harrison DE, et al. "Rapamycin fed late in life extends lifespan in genetically heterogeneous mice." Nature. 2009;460(7253):392-5. PubMed · DOI
- 8Moel M, et al. "Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results." Aging (Albany NY). 2025;17(4):908-936. PubMed · DOI
- 9Konopka AR, et al. "Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults." Aging Cell. 2019;18(1):e12880. PubMed · DOI
- 10Davidson KW, et al. "Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement." JAMA. 2022;327(16):1577-1584. PubMed · DOI
