Trial
Metformin in Longevity Study (MILES)
Source Summary
8 reviewed sources across 4 evidence layers.
- Trial registry2
- Peer-reviewed publications2
- Dataset / repository1
- Review / contextual sources3
Trial Snapshot
ClinicalTrials.gov identifier.
Lead sponsor listed by the registry.
Registry status; not an efficacy classification.
Registry classification; not a longevity-evidence grade.
ClinicalTrials.gov design fields.
Participant and investigator masked.
Metformin and placebo treatment periods.
Registry count; the publication reports analyses in 14 participants.
Narrow eligibility; not a general healthy population.
Trial description only; no dosing or use guidance.
Short exposure reported in the publication.
Posted results do not establish broad longevity benefit.
Registry, publication, dataset, and context links rechecked.
Critical review and TAME context are separated.
Confidence applies to the narrow evidence map.
Executive Summary
MILES studied short-term metformin exposure in a small randomized, double-masked, placebo-controlled crossover trial involving older adults with impaired glucose tolerance. ClinicalTrials.gov records 16 actual participants, while the linked publication reports analyses in 14 participants after six weeks in each treatment period. The evidence centers on skeletal muscle and subcutaneous adipose transcriptomic and metabolic readouts. MILES was not a longevity-outcome trial and is separate from TAME.
Why It Matters
MILES connects a public trial registry, a peer-reviewed human mechanistic analysis, and an open transcriptomic dataset. It is useful for distinguishing molecular readouts from validated clinical or longevity outcomes, and for examining how study design, tissue context, and endpoint selection affect trial-readiness judgments.
Trial Design
| Design field | Registered / reported value | Source | Limitation |
|---|---|---|---|
| Study design | Phase 4 interventional, randomized, double-masked, placebo-controlled crossover trial | ClinicalTrials.gov; publication | Design strength does not overcome the small sample or short exposure. |
| Allocation | Randomized | ClinicalTrials.gov | Randomization does not establish generalizability. |
| Intervention model | Crossover | ClinicalTrials.gov | Each participant serves as a comparison across short treatment periods. |
| Masking | Double; participant and investigator | ClinicalTrials.gov | Masking does not convert molecular readouts into clinical outcomes. |
| Population | Adults age 60+ with impaired glucose tolerance | ClinicalTrials.gov; publication | Not representative of all older adults or healthy consumers. |
| Enrollment | 16 actual enrolled; publication analysis reports n=14 | ClinicalTrials.gov; PMID 29383869 | Small sample limits inference and subgroup analysis. |
| Intervention | Metformin and placebo treatment periods | ClinicalTrials.gov; publication | Trial description is not treatment or dosing guidance. |
| Exposure period | 6 weeks in each treatment period | PMID 29383869 | Too short to assess longevity or long-term clinical outcomes. |
| Tissue / readout context | Skeletal muscle and subcutaneous adipose tissue; mixed-meal metabolic testing | PMID 29383869; GSE107894 | Tissue and metabolic readouts are mechanistic, not validated longevity endpoints. |
| Primary registered outcome | RNA-seq expression changes in muscle and adipose tissue after 6 weeks | ClinicalTrials.gov | A registered molecular outcome, not a validated surrogate or clinical endpoint. |
Endpoint and Readout Map
| Endpoint / readout | Category | Source | What it supports | Limitation |
|---|---|---|---|---|
| Increase in expressed genes in muscle and adipose tissue using RNA-seq | Registered primary mechanistic outcome | ClinicalTrials.gov | The prespecified molecular focus and tissue context. | Not a clinical endpoint, validated surrogate endpoint, or longevity outcome. |
| Differential gene expression in skeletal muscle and adipose tissue | Publication-supported mechanistic readout | PMID 29383869; PMC5847877 | Reported transcriptomic changes in the analyzed sample. | Small, short study; does not establish clinical utility or benefit. |
| Metabolic and nonmetabolic pathway analyses | Exploratory analysis | PMID 29383869; GSE107894 | Pathway-level interpretation of the transcriptomic dataset. | Exploratory pathway findings require independent validation. |
| Mixed-meal tolerance and insulin sensitivity / secretion measures | Registered secondary metabolic outcome | ClinicalTrials.gov; PMID 29383869 | Short-term metabolic-response context. | Does not establish disease prevention, treatment benefit, or longevity benefit. |
| Morbidity, mortality, or clinical event outcomes | Clinical outcome not measured | Registry and publication scope | A clear boundary on interpretation. | No clinical-event conclusion can be drawn. |
| Lifespan, healthspan, or validated aging-surrogate outcomes | Longevity outcome not measured | Registry and publication scope | A clear longevity-evidence boundary. | No MILES measure should be presented as a validated aging surrogate. |
Results and Publication Context
ClinicalTrials.gov NCT02432287
Establishes registered design, sponsor, status, enrollment, outcomes, and results availability. It does not establish broad efficacy or longevity benefit.
PubMed PMID 29383869
Indexes the Aging Cell report of transcriptomic and metabolic analyses in the small crossover study. Publication does not establish long-term clinical benefit.
PMC5847877
Provides the full publication context, methods, analyses, and stated limitations. Full-text availability does not expand the study outcomes.
NCBI GEO GSE107894
Supports dataset transparency and reanalysis of the reported expression data. Dataset availability is not clinical validation.
PubMed PMID 34421827
Provides broader critical context for metformin and aging claims. It is not a MILES result source and does not validate MILES endpoints.
PMC8374068
Provides accessible review context and limitations around anti-aging interpretations. It does not add trial outcomes to MILES.
AFAR TAME context
Used only to distinguish TAME from MILES. TAME is not a MILES result, endpoint, or evidence substitute.
Timeline / Milestones
-
Study start
ClinicalTrials.gov
Registry milestone; not an outcome.
-
Registry record first posted
ClinicalTrials.gov
Public registration timing.
-
Primary completion
ClinicalTrials.gov
Completion does not indicate benefit.
-
Study completion and GEO dataset availability
ClinicalTrials.gov; NCBI GEO
Dataset availability supports transparency, not clinical validation.
-
Aging Cell publication and registry results posting
PMID 29383869; ClinicalTrials.gov
Reported molecular and metabolic analyses remain narrow in scope.
-
LongevityNext source review
Registry, publication, dataset, and context links
Review confirms source availability and claim boundaries, not new trial evidence.
Source Posture
Trial registry
ClinicalTrials.gov establishes registered trial facts and posted-results availability, not broad benefit.
Peer-reviewed publication
The Aging Cell paper supports the reported molecular and metabolic analyses in the analyzed sample.
Open dataset
GEO provides the associated expression dataset; availability does not validate a clinical endpoint.
Critical review context
The review supports caution around extending mechanistic evidence into anti-aging claims.
TAME contextual source
AFAR context is used only to keep the separate TAME initiative distinct from MILES.
Evidence / Claim Boundary
Registry-supported trial facts
Identity, sponsor, phase, design, status, enrollment, registered outcomes, and posted-results availability.
Publication-supported findings
Reported transcriptomic and metabolic analyses in a small, short crossover study.
Dataset-supported context
Associated expression data are publicly available for inspection and reanalysis.
Not a validated longevity endpoint
No registered or reported MILES measure is treated here as a validated aging surrogate or longevity outcome.
Not evidence for consumer use
The record does not support treatment, prevention, dosing, or personalized-use guidance.
What This Can Support
Mechanistic human-trial context
A narrow example of a human crossover study centered on molecular and metabolic readouts.
Transcriptomic pathway discussion
Careful discussion of tissue-specific expression and pathway analyses reported by the study.
Endpoint-readiness analysis
Assessment of the distance between molecular readouts and validated clinical or longevity outcomes.
Trial-design comparison
Comparison of crossover design, masking, population, exposure period, and endpoint selection.
Research evidence mapping
Separation of registry facts, publication analyses, dataset availability, and contextual review evidence.
What This Does Not Prove
Longevity or healthspan benefit
MILES does not establish lifespan extension, healthspan benefit, mortality reduction, or delayed morbidity.
Disease prevention or clinical utility
The record does not establish disease-prevention benefit, clinical decision usefulness, or a validated aging-surrogate endpoint.
Treatment or consumer guidance
The record does not provide a treatment recommendation, dosing guidance, consumer-use conclusion, or personalized advice.
TAME evidence
MILES is not TAME and cannot substitute for TAME design, endpoints, or future results.
Detailed Sources
View detailed source table
Trial registry
| Source | Type | Supports | Limitation | Link |
|---|---|---|---|---|
| Metformin in Longevity Study (MILES) - NCT02432287 | Clinical trial registry | Trial identity, sponsor, design, status, enrollment, outcomes, and posted-results availability. | Registry facts do not establish broad efficacy or longevity benefit. | Open registry |
| ClinicalTrials.gov API - NCT02432287 | Structured registry record | Machine-readable protocol and results modules. | Structured availability does not change the evidence stage. | Open API record |
Peer-reviewed publications
| Source | Type | Supports | Limitation | Link |
|---|---|---|---|---|
| Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults | PubMed publication record | Publication identity and reported mechanistic analyses. | Small analyzed sample and short exposure; no longevity outcome. | PubMed PMID 29383869 |
| PMC5847877 full text | Open full-text publication | Methods, analyses, and full publication context. | Full text does not expand the measured outcomes. | Open PMC5847877 |
Dataset / repository
| Source | Type | Supports | Limitation | Link |
|---|---|---|---|---|
| NCBI GEO GSE107894 | Open transcriptomic dataset | Public expression data associated with the MILES analysis. | Dataset transparency is not clinical or surrogate-endpoint validation. | Open GSE107894 |
Review / contextual sources
| Source | Type | Supports | Limitation | Link |
|---|---|---|---|---|
| A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug | PubMed critical review record | Caution around broad metformin and aging interpretations. | Not a MILES result source and does not validate MILES endpoints. | PubMed PMID 34421827 |
| PMC8374068 full-text critical review | Open critical review | Accessible critical context for evidence limitations. | Does not add outcomes to MILES. | Open PMC8374068 |
| AFAR Targeting Aging with Metformin (TAME) | Contextual initiative page | Separation of the distinct TAME initiative from MILES. | Not a MILES result, endpoint, or evidence substitute. | Open AFAR TAME context |
Confidence / Methodology
Editorial status
Editorial review complete; source freshness checked
Evidence separation
Registry design and status facts, publication-reported analyses, open-dataset availability, and critical context were reviewed as separate evidence layers. A result or dataset was not treated as a validated clinical, surrogate, or longevity endpoint.
Last reviewed
2026-07-11