Living evidence page · Drugs & supplements
Metformin
Metformin is established for type 2 diabetes. Diabetes-prevention results and small mechanistic aging studies answer different questions; neither establishes longer healthy human life.
Safety and regulatory context: Healthy-aging use is off-label. The US label includes a boxed warning for lactic acidosis; kidney function, interacting drugs, contrast, surgery, hypoxia, alcohol use, liver impairment, vitamin B12 and gastrointestinal effects matter clinically.
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Three different evidence questions
Counts and order describe what More Years has released. They do not indicate evidence strength, efficacy, safety, importance, popularity or recommendation.
Released reporting
What the covered evidence says
Other human evidence · Human biomarkers and muscle · small trials
Metformin is established for diabetes—not for extending healthy human life
- Population
- Healthy adults age 65 or older, including a 14-person crossover sample around age 70
- Measured
- muscle adaptation, metabolism and gene expression
Small older-adult studies show mechanistic changes and a blunted hypertrophy signal, not healthspan or lifespan extension.
Does not establish: Metformin is established for diabetes—not for extending healthy human life
Published 2026-07-31 · verified 2026-07-31
Large randomized trial · Human diabetes incidence and microvascular outcomes · long randomized follow-up
DPP prevention effects persisted for 15 years—without an overall microvascular difference
- Population
- 2,776 surviving DPP participants with elevated glucose and overweight or obesity who joined long-term follow-up
- Measured
- cumulative type 2 diabetes incidence and aggregate microvascular disease
Over 15 years, cumulative diabetes incidence was 55% with intensive lifestyle, 56% with metformin and 62% with placebo. The randomized groups did not differ significantly in aggregate microvascular prevalence.
Does not establish: The follow-up did not demonstrate that either randomized assignment reduced the aggregate microvascular outcome or extended life.
Published 2026-08-26 · verified 2026-08-26
Primary publications and governing syntheses
3 covered studies
These records preserve identifiers, populations, outcomes and interpretation boundaries from the released evidence library.
Randomized trial · peer-reviewed
Metformin Tissue Crossover
DOI: 10.1111/acel.12723
- Population
- 14 approximately 70-year-old participants
- Measured
- glucose and insulin responses; muscle and adipose gene expression
- Result in released coverage
- The reviewed human evidence does not establish that metformin extends lifespan in healthy people.
- Evidence maturity
- small human mechanistic/function trials; no healthy-human longevity trial result
- Funding / conflicts
- paper funding and disclosures required
- Limitations
- very small sample · short exposure · mechanistic endpoints · no clinical outcome · condition-specific diabetes evidence and ongoing trials answer different questions
The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Verified 2026-07-31 · correction state: none
Randomized trial · peer-reviewed
Masters Metformin Training
DOI: 10.1111/acel.13039
- Population
- 94 healthy adults aged 65 or older during 14 weeks of supervised progressive resistance training
- Measured
- lean mass; thigh muscle mass; muscle area and density; strength
- Result in released coverage
- During 14 weeks of supervised resistance training in healthy adults aged 65 or older, the metformin group gained less lean and thigh muscle mass than placebo. · The reviewed human evidence does not establish that metformin extends lifespan in healthy people.
- Evidence maturity
- small human mechanistic/function trials; no healthy-human longevity trial result
- Funding / conflicts
- NIA R01AG046920 and NCATS UL1TR001998/UL1TR003096; paper disclosures required
- Limitations
- short duration · healthy selected volunteers · training-adaptation endpoints · not a morbidity or lifespan trial · short trial · selected volunteers · hypertrophy is not healthspan · strength difference was not statistically significant · condition-specific diabetes evidence and ongoing trials answer different questions
The measured result does not establish a general longevity benefit beyond the population, design and outcomes reported.
Verified 2026-07-31 · correction state: none
Randomized trial · peer-reviewed
DPPOS 15-year diabetes and microvascular outcomes
PMID: 26377054
- Population
- Adults with impaired glucose tolerance and BMI at least 24 kg/m² in the original DPP cohort
- Measured
- Diabetes incidence; Aggregate retinopathy, nephropathy and neuropathy prevalence; Aggregate microvascular prevalence
- Result in released coverage
- At 15 years, cumulative diabetes incidence was 55% with lifestyle, 56% with metformin and 62% with placebo; hazard ratios were 0.73 and 0.82 versus placebo. · Overall aggregate microvascular prevalence did not differ significantly by original randomized group: 11.3% lifestyle, 13.0% metformin and 12.4% placebo. · Women-only differences and the lower prevalence among participants who did not develop diabetes are secondary subgroup or exposure-defined findings.
- Evidence maturity
- Long randomized follow-up with diabetes incidence benefit and an overall null aggregate microvascular comparison
- Funding / conflicts
- NIDDK/NIH support; governing paper declares no conflicts.
- Limitations
- Post-DPP lifestyle exposure across groups, unmasked follow-up treatment and diminishing separation · End-study prevalence composite and shared lifestyle exposure · Multiplicity, subgroup scope and nonrandomized diabetes-status comparison
No demonstrated cardiovascular, mortality, healthspan or lifespan benefit · No overall randomized microvascular benefit · No whole-cohort randomized microvascular effect
Verified 2026-08-26 · correction state: none-linked-as-of-2026-08-26
Registry records
4 connected clinical trials
Status and results availability are kept separate from evidence conclusions.
Completed · Not assessed
intensive lifestyle or metformin for diabetes prevention — NCT00004992
- Population
- 2,776 surviving DPP participants with elevated glucose and overweight or obesity who joined long-term follow-up
- Intervention / comparator
- randomized lifestyle or metformin versus placebo, followed observationally after the original trial
- Primary outcome
- cumulative type 2 diabetes incidence and aggregate microvascular disease
- Sponsor / funding context
- Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Registry status is operational information, not evidence of benefit.
Status checked 2026-08-26 · registry link checked 2026-08-27
Active, not recruiting · Not assessed
intensive lifestyle or metformin for diabetes prevention — NCT00038727
- Population
- 2,776 surviving DPP participants with elevated glucose and overweight or obesity who joined long-term follow-up
- Intervention / comparator
- randomized lifestyle or metformin versus placebo, followed observationally after the original trial
- Primary outcome
- cumulative type 2 diabetes incidence and aggregate microvascular disease
- Sponsor / funding context
- Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Registry status is operational information, not evidence of benefit.
Status checked 2026-08-27 · registry link checked 2026-08-27
Completed · Peer-reviewed publication linked
Metformin to Augment Strength Training Effective Response in Seniors (MASTERS)
- Population
- Healthy adults age 65 or older, including a 14-person crossover sample around age 70
- Intervention / comparator
- small trials
- Primary outcome
- muscle adaptation, metabolism and gene expression
- Sponsor / funding context
- Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Registry status is operational information, not evidence of benefit.
Status checked 2026-07-31 · registry link checked 2026-08-27
Active, not recruiting · Not assessed
Metformin to Prevent Inactivity-induced Loss of Muscle Health During Aging
- Population
- Healthy adults age 65 or older, including a 14-person crossover sample around age 70
- Intervention / comparator
- small trials
- Primary outcome
- muscle adaptation, metabolism and gene expression
- Sponsor / funding context
- Funding and conflict context is source-reviewed in the linked article; registry sponsorship alone is not evidence of benefit.
Registry status is operational information, not evidence of benefit.
Status checked 2026-08-27 · registry link checked 2026-08-27
Coverage timeline
When this reporting was released
- Metformin is established for diabetes—not for extending healthy human lifeHuman biomarkers and muscle · small trials
- DPP prevention effects persisted for 15 years—without an overall microvascular differenceHuman diabetes incidence and microvascular outcomes · long randomized follow-up