This page shows what was measured, who it was measured in, and what that does not settle.
What Metformin does in the body
Type 2 diabetes, and blood sugar that is too high
Your liver makes sugar and releases it into the blood between meals. Metformin gets carried into liver cells by a specific transporter, mildly slows one step of their energy production, and the cell reads that dip as a signal that it cannot afford to be manufacturing sugar. Output falls. It does not push insulin out of the pancreas, which is why it does not cause low blood sugar on its own.
What happened in people
A 19% reduction in serum vitamin B12 against placebo over 4.3 years, with a 7.2 percentage-point absolute increase in frank deficiency
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
The limit that matters most
That metformin slows ageing or extends lifespan in humans — TAME was designed in 2016, has no registration and has never enrolled anyone
Where it acts
Hepatocyte mitochondria and cytoplasm (liver)
Kind of result
A number that stands in for health
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
Its recorded molecular formula is C4H11N5∙HCl, weighing 165.63.
US prescribing information · 07b4ee2a-8435-4d38-a6b0-b919e3424153 · read 2026-08-30
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 106 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Formulation
A formulation is the exact made-up form a substance comes in.
A picture of it, and where the picture fails
It is like the difference between a whole bean and instant coffee.
Where that stops being true. Coffee tastes different. A formulation can change how much reaches the blood.
What people get wrong. Two products with the same name are assumed to behave the same. They often do not.
The specific composition and physical form of a product, including salt, excipients and release profile.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Blood sugar
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
△Only a number moved12 registered test measure.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Fertility and sexual health
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Blood sugar
development of diabetes; diabetes; hba1c at week 24; hba1c; hba1c at 52 weeks; time to hba1c 8; effect on hba1c levels; hba1c following two years of treatment
Fertility and sexual health
free testosterone
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
△ Only a number moved
12 registered test measure.
— Not recorded
Harms were not a registered measure for this goal.
… Waiting for a reviewer
Who was studied is listed further down the page.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Aggregate of any diabetes-related clinical endpoint, diabetes-related death and all-cause mortality
✓ The study showed what it set out to show
Who was studied
UKPDS 34 (metformin versus conventional policy)
How many people
753
Study design
Randomised controlled trial, median 10.7 years
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
P = 0.002 for any diabetes-related endpoint; P = 0.011 for all-cause mortality
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, immediate-release and extended-release, and an oral solution
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
VA-IMPACT: Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular Outcomes (NCT02915198) · a recorded source, not a stored snapshot
Diabetes-related death with metformin added to maximum sulfonylurea therapy
✗ The study did not show it
Who was studied
UKPDS 34 supplementary randomisation (metformin added to sulfonylurea)
How many people
537
Study design
Randomised controlled trial
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
P = 0.039 for a 96% increased risk of diabetes-related death
Repeated elsewhere
Failed to Replicate
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The harm signal is in the published abstract. The same paper reports an epidemiological analysis across 4,416 patients showing no such risk, and the investigators favoured chance as the explanation.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, immediate-release and extended-release, and an oral solution
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
VA-IMPACT: Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular Outcomes (NCT02915198) · a recorded source, not a stored snapshot
Percentage change in vitamin B12, folate and homocysteine from baseline
✓ The study showed what it set out to show
Who was studied
de Jager vitamin B12 trial (NCT00375388)
How many people
390
Study design
Phase 4 randomised placebo-controlled trial, 4.3 years
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
P < 0.001 for the 19% reduction in vitamin B12
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, immediate-release and extended-release, and an oral solution
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
VA-IMPACT: Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular Outcomes (NCT02915198) · a recorded source, not a stored snapshot
Change in whole-body insulin sensitivity and skeletal muscle mitochondrial respiration after aerobic training
✗ The study did not show it
Who was studied
Konopka exercise-interaction trial
How many people
53
Study design
Double-blind randomised trial, 12 weeks
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Metformin attenuated the training-induced rise in insulin sensitivity and VO2 max and abrogated the mitochondrial response
Repeated elsewhere
Partially Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Responses were bimodal: the metformin arm contained both positive and negative responders, and the group mean hides that.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, immediate-release and extended-release, and an oral solution
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
VA-IMPACT: Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular Outcomes (NCT02915198) · a recorded source, not a stored snapshot
Time to death, non-fatal myocardial infarction, stroke, hospitalisation for unstable angina or symptom-driven coronary revascularisation
✗ The study did not show it
Who was studied
VA-IMPACT (NCT02915198)
How many people
7410
Study design
Phase 4 cardiovascular outcome trial
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Not reported — recruiting, estimated completion 28 September 2029
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. The trial has not reported. `endpoint met: false` here means "no result exists yet", not "the endpoint was missed".
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, immediate-release and extended-release, and an oral solution
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
VA-IMPACT: Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular Outcomes (NCT02915198) · a recorded source, not a stored snapshot
Composite time to first incident age-related chronic disease — as designed, never measured
✗ The study did not show it
Who was studied
TAME (Targeting Aging with Metformin)
How many people
0
Study design
Designed but never launched
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
No result. No ClinicalTrials.gov registration and no participants enrolled as of August 2026.
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. This row exists because TAME is cited in popular writing as though it were running. A sample size of zero is the accurate entry.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral tablet, immediate-release and extended-release, and an oral solution
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
VA-IMPACT: Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular Outcomes (NCT02915198) · a recorded source, not a stored snapshot
What we know
RNAWiki holds 6 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
■Living longer, or avoiding a major eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.1 registered measure of this kind. 2 written-up studies measured this and did not show a benefit.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
□Symptoms and quality of lifeNo evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.18 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Yeast, C. elegans (roundworm), Drosophila (fruit fly), Mouse, Rat, Dog, Non-human primate. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Where a source records it acting
Liver: Decreases hepatic glucose production
US prescribing information · 356b02d0-d239-4441-bb33-c4c54166fcd7 · read 2026-08-27
Intestines: Decreases intestinal absorption of glucose
US prescribing information · 356b02d0-d239-4441-bb33-c4c54166fcd7 · read 2026-08-27
Start
Metformin
What a person takes: Oral tablet, immediate-release and extended-release, and an oral solution.
The measurement behind this step
Taken with food to reduce gastrointestinal effects. The extended-release formulation exists because the immediate-release one causes diarrhoea and nausea in a substantial minority in the first weeks, and that intolerance is the commonest reason people stop.
Getting in
Swallowed, absorbed slowly, and never metabolised
The tablet dissolves in the upper gut and is absorbed over several hours. The body does not break the molecule down at all: whatever goes in comes out unchanged in the urine.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Absolute oral bioavailability of roughly 50 to 60%, absorption largely complete within six hours, no hepatic metabolism and no plasma protein binding. Elimination is entirely renal by active tubular secretion, which is why declining kidney function raises exposure and why the label is written around eGFR.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
Reaching the cell
A transporter carries it into liver cells
Metformin carries a positive charge and cannot slip through a cell membrane on its own. A specific pump on the liver-cell surface pulls it in, which is why the liver sees far more of it than the rest of the body.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Organic cation transporter 1 (OCT1, SLC22A1) moves metformin across the hepatocyte sinusoidal membrane; MATE1 and MATE2-K handle biliary and renal efflux. Reduced-function OCT1 variants blunt the glucose-lowering effect, which is the cleanest evidence that hepatic uptake is rate-limiting.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
What it acts on
It gathers in the mitochondria and mildly slows one step
Inside the cell, the positive charge drags metformin into the mitochondria, where it accumulates far above its concentration in blood and gently slows the first step of energy production.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The membrane potential across the inner mitochondrial membrane concentrates the cation several hundred-fold in the matrix, where it inhibits complex I (NADH:ubiquinone oxidoreductase). The inhibition is partial and reversible; the intracellular concentration required is millimolar, far above the micromolar plasma concentration, which is the whole reason the transporter step matters.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
The change it makes
The cell reads a fall in energy charge and stops making sugar
A small drop in cellular energy switches on a sensor that tells the cell to stop expensive manufacturing. Making glucose from scratch is expensive, so it stops.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The rising AMP to ATP ratio activates AMPK via LKB1-dependent phosphorylation at Thr172 and, independently of AMPK, AMP inhibits fructose-1,6-bisphosphatase and adenylate cyclase. Hepatic gluconeogenesis falls through reduced PEPCK and G6Pase transcription and reduced glucagon signalling. Which of these branches dominates in humans is still argued in the literature.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
What that does for a person
Fasting glucose falls, without pushing insulin out
Blood sugar comes down because the liver is releasing less of it, not because more insulin is being forced out of the pancreas. That is why metformin alone almost never causes a hypo.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Reduced hepatic glucose output lowers fasting plasma glucose and HbA1c without stimulating pancreatic beta cells. In UKPDS 34 the achieved median HbA1c was 7.4% against 8.0% on conventional policy, and severe hypoglycaemia was less frequent than with sulfonylureas or insulin.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
No registered study measured anything of this kind.
Measured
Things only a test, a scale or a device shows.
hba1c at week 24
hemoglobin a1c at week 24
hba1c
hba1c at 52 weeks
flow mediated dilation
time to hba1c 8
effect on hba1c levels
hemoglobin a1c changes from baseline at week 24
hba1c following two years of treatment
insulin sensitivity
and 8 more.
Meaningful
Things that change how a life goes, not only a number.
overall survival
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (21)
development of diabetes
primary major macrovascular events
diabetes
treatment failure
a1c at week 24
beta cell function after 52 weeks of therapy
safety
haemoglobina1c
glycemic control
a1c changes from baseline at week 24 open label cohort
free testosterone
a1c at month 6
gestational diabetes
preterm delivery
symptomatic hypoglycemia
severe hypoglycemia
beta cell function c peptide auc
time from randomization to the primary action
reduction in conversion of igt to diabetes
glycosylated a1c at week 26
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What it would be like to take◇Read from sources, not yet reviewed
How long anything takes
Nine different lengths of time that get confused with each other. None of them is worked out from another.
Before anything is noticed.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before a test result moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
Before performance moves.RNAWiki does not store this separately, and never works it out from another figure on this page.
How long the result was watched.No finished study window is recorded for a study that tested this substance.
How long people took it.How long people actually took it is not stored. The study window is not the same thing.
How long people were followed.Follow-up length is not stored separately. It is never read off the study window, which would be a different thing.
How fast the body clears it. approximately 6.2 hours hours
Read from the label, which states: “Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours.”
How long effects linger.RNAWiki does not store this separately, and never works it out from another figure on this page.
Beyond the studies. Nothing is recorded about the long term.
The longest finished study sets the edge of what anyone measured.
A study window is not how long people took it, and neither is how long they were followed. Where RNAWiki holds only one of the three, it shows one.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
First-line drug therapy for type 2 diabetes in essentially every major guideline, and widely used off-label in polycystic ovary syndrome. It is on the WHO Model List of Essential Medicines.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Safety and effectiveness of Metformin hydrochloride extended-release tablets in pediatric patients have not been established.”
US prescribing information · 07b4ee2a-8435-4d38-a6b0-b919e3424153 · read 2026-08-30
On older people, the label states: “Controlled clinical studies of Metformin hydrochloride extended-release tablets did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients.”
US prescribing information · 07b4ee2a-8435-4d38-a6b0-b919e3424153 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Limited data with Metformin hydrochloride extended-release tablets in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage.”
US prescribing information · 07b4ee2a-8435-4d38-a6b0-b919e3424153 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Limited published studies report that metformin is present in human milk [ see Data ].”
US prescribing information · 07b4ee2a-8435-4d38-a6b0-b919e3424153 · read 2026-08-30
On people with reduced liver function, the label states: “Use of metformin in patients with hepatic impairment has been associated with some cases of lactic acidosis.”
US prescribing information · 07b4ee2a-8435-4d38-a6b0-b919e3424153 · read 2026-08-30
On people with reduced kidney function, the label states: “Metformin is substantially excreted by the kidney, and the risk of metformin accumulation and lactic acidosis increases with the degree of renal impairment.”
US prescribing information · 07b4ee2a-8435-4d38-a6b0-b919e3424153 · read 2026-08-30
Where the result stopped carrying
The supplementary UKPDS randomisation: adding metformin to maximum sulfonylurea raised diabetes-related death by 96% (p=0.039)
Twelve weeks of aerobic training produced no mitochondrial adaptation in older adults taking metformin, and a blunted rise in VO2 max and insulin sensitivity
Phenformin, the earlier biguanide, was withdrawn for fatal lactic acidosis and left metformin with a contraindication the evidence never supported
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
A different form was studied
The studied form is not the form on the shelf.
On this record: This record is linked to 1 related forms. Evidence does not carry across all of them.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (9)
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral tablet, immediate-release and extended-release, and an oral solution
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S6.
No source is stored against this line.
What is in the pack
Taken with food to reduce gastrointestinal effects. The extended-release formulation exists because the immediate-release one causes diarrhoea and nausea in a substantial minority in the first weeks, and that intolerance is the commonest reason people stop.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
The US label carries a boxed warning for lactic acidosis, with risk factors of renal impairment, concomitant drugs affecting renal function, age 65 and older, radiological contrast studies, surgery, hypoxic states, excessive alcohol and hepatic impairment. The pooled trial and cohort evidence found no excess of lactic acidosis at therapeutic doses. Common effects are diarrhoea, nausea and abdominal discomfort. Long-term use lowers vitamin B12, and the label recommends periodic measurement.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
American Federation for Aging Research — TAME (Targeting Aging with Metformin) programme page (https://www.afar.org/tame-trial) · a recorded source, not a stored snapshot
Reports sent to a regulator
These are reports people sent to a regulator. They do not show the medicine caused the reaction.
Nobody counted how many people took the medicine and reported nothing.
The same event can be reported more than once, and many reports are incomplete.
News coverage, lawsuits and new warnings change how often people report.
A count is not a rate and not a risk.
Metformin appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 28218 reaction mentions were counted. One report can name several reactions.
The recorded terms (10)
lactic acidosis — 7697 reaction mentions
acute kidney injury — 5387 reaction mentions
hypoglycaemia — 2567 reaction mentions
diarrhoea — 2429 reaction mentions
metabolic acidosis — 2428 reaction mentions
vomiting — 1964 reaction mentions
toxicity to various agents — 1927 reaction mentions
hypotension — 1394 reaction mentions
hyperkalaemia — 1327 reaction mentions
renal failure — 1098 reaction mentions
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral tablet, immediate-release and extended-release, and an oral solution
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
The extended-release formulation exists because the immediate-release one causes diarrhoea and nausea in a substantial minority in the first weeks, and that intolerance is the commonest reason people stop.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
739 products list this as an active ingredient in the United States drug directory. 504 of them contain it and nothing else.
FDA National Drug Code directory · 71610-587 · read 2026-08-29
They are sold as granule, powder, solution, tablet, tablet, coated and tablet, extended release, taken oral.
FDA National Drug Code directory · 71610-587 · read 2026-08-29
The regulator's established pharmacologic class for it is biguanide [epc] and biguanides [cs].
FDA National Drug Code directory · 71610-587 · read 2026-08-29
390 published labels name it as an active ingredient. 316 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 07b4ee2a-8435-4d38-a6b0-b919e3424153 · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 07b4ee2a-8435-4d38-a6b0-b919e3424153 · read 2026-08-29
6 marketed supplement labels list this ingredient, classed as other combinations and vitamin.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
metformin hydrochloride is extended-release tablets at Extended-Release Tablets: 500 mg and 1,000 mg, recorded as prescription product; fda label in effect 2026-01-15 in the United States.
US prescribing information · 356b02d0-d239-4441-bb33-c4c54166fcd7 · read 2026-08-27
Recorded price in US: 0.01419–14.605 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 168 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Recorded price in US: 0.37295 USD per one millilitre, across 4 priced products whose strengths and pack forms differ, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
Over a median of nearly eleven years, overweight patients randomised to metformin had a third fewer deaths from any cause than those managed by diet alone. This is the drug's one hard-outcome result and nothing since has repeated it.
What was measured
All-cause mortality and aggregate diabetes-related endpoints at median 10.7 years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Of 1,704 overweight patients with newly diagnosed type 2 diabetes, 753 entered the randomised comparison: intensive control with metformin (n=342) versus conventional policy, primarily diet (n=411), median 10.7 years. Median HbA1c was 7.4% on metformin against 8.0% on conventional therapy. Risk reductions were 32% for any diabetes-related endpoint (95% CI 13 to 47, p=0.002), 42% for diabetes-related death (9 to 63, p=0.017) and 36% for all-cause mortality (9 to 55, p=0.011). Against the other intensive arms, metformin beat chlorpropamide, glibenclamide and insulin for any diabetes-related endpoint (p=0.0034), all-cause mortality (p=0.021) and stroke (p=0.032).
Written into the record, not signed off as a reviewed claim
The longevity claim rests on a trial that has never enrolled a single participant
In plain words
TAME, the trial designed to test whether metformin slows ageing, has been designed and publicised for a decade and has never started. Every statement that metformin extends healthy lifespan in people is an extrapolation.
What was measured
That metformin extends healthy lifespan or slows ageing in humans — a hypothesis with a published trial design, no trial, and no result
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
TAME (Targeting Aging with Metformin) was proposed by Barzilai and colleagues in Cell Metabolism in 2016 as a six-year, roughly 3,000-participant trial using a composite of incident age-related disease as its endpoint, coordinated through the American Federation for Aging Research. As of August 2026 it has no ClinicalTrials.gov registration, no enrolment and no completed funding: a search of the ClinicalTrials.gov v2 API for the trial title returns no matching study. The one large randomised trial actually running on a non-diabetic outcome is VA-IMPACT (NCT02915198), a 7,410-participant phase 4 trial of metformin in prediabetes with established atherosclerotic disease, recruiting, with an estimated completion date of 28 September 2029.
Written into the record, not signed off as a reviewed claim
The cancer-prevention literature collapsed once immortal time bias was removed
In plain words
From 2005 onwards, dozens of observational studies reported that metformin users got much less cancer. In 2012 the statistical flaw producing that pattern was identified. Studies that avoid it find nothing, and the randomised trials find nothing.
What was measured
That metformin prevents or treats cancer — an inference from cohort studies whose design produced the effect
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Suissa and Yu reviewed the field in Diabetes Care in 2023 under the title "Metformin and Cancer: Solutions to a Real-World Evidence Failure". The observational signal was driven by time-related biases, principally immortal time bias, which systematically exaggerates a drug's apparent benefit. Observational studies designed to avoid those biases found no association. Randomised trials of metformin as adjuvant cancer therapy likewise found no reduction in incidence or outcomes, and the largest — a phase 3 adjuvant breast cancer trial of 3,649 women with five-year follow-up — found no benefit for disease-free or overall survival. The authors note the same preventable biases were still prominent in the 2022 literature.
Written into the record, not signed off as a reviewed claim
Adding metformin to sulfonylurea nearly doubled diabetes-related death in UKPDS 34
In plain words
The same paper that found the mortality benefit also found harm. In a separate randomisation, patients already on maximum sulfonylurea who had metformin added had a 96% higher risk of dying from a diabetes-related cause.
What was measured
Diabetes-related death in the sulfonylurea-plus-metformin randomisation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
The supplementary randomised comparison in UKPDS 34 allocated 537 patients already receiving maximum sulfonylurea therapy with raised fasting plasma glucose to continued sulfonylurea alone (n=269) or the addition of metformin (n=268). Early addition of metformin was associated with a 96% increased risk of diabetes-related death (95% CI 2 to 275, p=0.039). The investigators then ran an epidemiological assessment across 4,416 patients and found no increased risk of diabetes-related death on combination therapy (risk reduction 5%, 95% CI -33 to 32, p=0.78), and treated the randomised finding as most likely a chance result. Both analyses are in the same paper; the randomised one is the one with the randomisation.
Written into the record, not signed off as a reviewed claim
Metformin blocked the mitochondrial gains from exercise training in older adults
In plain words
In a double-blind trial, older adults who exercised for twelve weeks improved their fitness and insulin sensitivity. Those who took metformin alongside the training did not improve as much, and their muscle mitochondria did not adapt at all.
What was measured
Change in VO2 max, whole-body insulin sensitivity and mitochondrial respiration after 12 weeks of training
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Konopka et al. randomised 53 adults with a mean age of 62 to placebo (n=26) or metformin (n=27) during twelve weeks of aerobic exercise training. Training reduced fat mass, HbA1c, fasting insulin, 24-hour mean glucose and glycaemic variability irrespective of treatment. Metformin attenuated the increase in whole-body insulin sensitivity and in VO2 max after training, and abrogated the training-induced rise in skeletal muscle mitochondrial respiration. The change in insulin sensitivity correlated with the change in mitochondrial respiration. Responses were highly variable, with both positive and negative responders in the metformin arm. The authors conclude that more work is needed before metformin is prescribed to slow ageing.
Written into the record, not signed off as a reviewed claim
B12 deficiency is a real, randomised, dose-of-time-dependent harm
In plain words
Over more than four years, metformin lowered vitamin B12 levels by about a fifth compared with placebo, and pushed roughly one person in fourteen into outright deficiency.
What was measured
Percentage change in serum vitamin B12 and absolute risk of deficiency at 4.3 years
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
De Jager et al. randomised 390 insulin-treated patients with type 2 diabetes to metformin 850 mg three times daily or placebo for 4.3 years. Metformin produced a mean 19% decrease in vitamin B12 (95% CI -24% to -14%, p<0.001) and a 5% decrease in folate. The absolute risk of B12 deficiency below 150 pmol/L was 7.2 percentage points higher on metformin (95% CI 2.3 to 12.1, p=0.004), a number needed to harm of 13.8 over 4.3 years; the risk of a low B12 of 150 to 220 pmol/L was 11.2 points higher (p=0.001). Homocysteine rose 5% (95% CI -1% to 11%, p=0.091).
Written into the record, not signed off as a reviewed claim
The lactic acidosis contraindication did not survive its own evidence review
In plain words
Metformin was kept away from patients with heart, kidney and lung disease for decades on the grounds that it caused a dangerous build-up of lactic acid. Pooling 347 studies found not one case, in either arm.
What was measured
That metformin causes clinically meaningful lactic acidosis at therapeutic doses — a class inference carried over from phenformin that the pooled data do not support
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Salpeter et al. pooled 347 comparative trials and cohort studies in the Cochrane review and found no case of fatal or non-fatal lactic acidosis in 70,490 patient-years of metformin use, nor in 55,451 patient-years of non-metformin comparators. By Poisson statistics the upper bound on the true incidence was 4.3 cases per 100,000 patient-years on metformin and 5.4 on comparators. Blood lactate did not differ, either as a mean level or as change from baseline. The contraindication that produced the original fear belonged to phenformin, a different biguanide withdrawn in the 1970s; the FDA replaced metformin's creatinine-based renal contraindication with an eGFR-based one in 2016.
Written into the record, not signed off as a reviewed claim
Metformin users outliving non-diabetic controls is an observational finding, not a drug effect
In plain words
A widely quoted UK database study found that people starting metformin lived longer than matched people without diabetes at all. It is not a trial, and who gets prescribed metformin is not random.
What was measured
That metformin confers a survival advantage over having no diabetes — an unadjustable healthy-user contrast presented as a drug effect
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Bannister et al. used the UK Clinical Practice Research Datalink to compare 78,241 patients started on metformin monotherapy, 12,222 started on sulfonylurea monotherapy, and 90,463 matched non-diabetic controls, over 503,384 censored person-years with 7,498 deaths. Taking metformin initiators as the reference, adjusted median survival time was 15% lower in matched non-diabetic controls (STR 0.85, 95% CI 0.81 to 0.90) and 38% lower in sulfonylurea initiators (0.62, 0.58 to 0.66). The design cannot separate a metformin effect from confounding by indication: metformin is preferentially started in patients with preserved renal function, no heart failure and no frailty, and those are the same people who would outlive the average person without diabetes anyway.
This order is fixed in code and does not count clicks or time on the page.
What is not here
3 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A 1950s biguanide that suppresses the liver's own glucose production, and the only glucose-lowering drug with a randomised all-cause mortality reduction in overweight type 2 diabetes — 36% in 753 patients in UKPDS 34, a result that has never been repeated and is routinely stretched into a longevity claim no trial has tested.
Recorded evidence blocks (15)
Q2
What did Metformin's largest trial (1499650 people) and its longest (26 years) measure?
1499650 people in Metformin's largest registered study, 26 years in its longest registered window, measuring Combined endpoint of all cause mortality and all cause hospitalization at 6 months. ClinicalTrials.gov · 2026-09-01
409 phase2, 388 phase3, 367 phase4, 340 phase1, 193 na, 46 early phase1, 43 na or unstated; NCT00038727; 2022-04-30. Last human test completed 2026, NCT07793838.
Interpretation These counts include studies where Metformin was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase2
409
phase3
388
phase4
367
phase1
340
na
193
early phase1
46
2 more recorded rows
na or unstated
43
Last recorded human testNCT07793838
2026-08-01
recorded 2026-09-01 · last checked 2026-09-04
Q3
From yeast to human: where has Metformin shown lifespan?
C. elegans: lifespan, Drosophila: lifespan, NHP: mechanism-only, yeast: lifespan, mouse: lifespan, rat: lifespan, dog: lifespan and human: lifespan (1693): the rungs where Metformin has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01
Combined endpoint of all cause mortality and all cause hospitalization at 6 months — the recorded outcome words.
Show the evidence
C. elegans
lifespan
Drosophila
lifespan
NHP
mechanism-only
yeast
lifespan
mouse
lifespan
rat
lifespan
2 more recorded rows
dog
lifespan
humanNCT00325910
lifespan; Combined endpoint of all cause mortality and all cause hospitalization at 6 months; 1693
recorded 2026-09-01 · last checked 2026-09-04
Q4
The NIA ITP gave Metformin at 1000 ppm and Met: 1000, Rapa: 14 from 9 months — did both sexes live longer?
612 mice; cohorts C2011; cohort rows are the workbook's own printed values; no median, percent change or survival statistic is derived from the per-animal data
Show the evidence
ITP cohort
C2011
metformin; 1000; 9 months; f, m; ITP_C2011_Lifespan.xlsx
C2011
metformin plus rapamycin; Met: 1000, Rapa: 14; 9 months; f, m; ITP_C2011_Lifespan.xlsx
"The development program has been terminated"; 173 of 1693 registered studies
Show the evidence
Trial
NCT00251953
terminated; "The development program has been terminated"
NCT00261352
terminated; "The development program has been terminated"
NCT00263965
terminated; "The development program has been terminated"
NCT00282945
terminated; "See statement in Detailed Description."
NCT00325910
terminated; "Insufficient study participants"
NCT00348712
terminated; "See termination reason in detailed description"
14 further recorded trials
NCT00362765
terminated; "The study was prematurely terminated, due to difficulties in the recruitment of T2DM patients who are not under statin therapy at inclusion."
terminated; "See termination reason in detailed description"
NCT00437970
withdrawn; "Unable to secure supply of the study medication"
NCT00449605
terminated; "Company decision taken in light of demands by certain national health authorities"
NCT00469586
terminated; "See termination reason in detailed description"
NCT00479466
terminated; "Sufficient data regarding the dose-response to MK-0893 had been obtained from the first cohort of the study to assess the safety and efficacy"
NCT00536211
withdrawn; "protocol not approved by VA R\&D"
NCT00571519
terminated; "DSPD focusing on Study 301 to confirm the clinical profile before proceeding. Daiichi Sankyo Pharma Development terminated this study on 23 Apr 2008 because of changes in the clinical development plan with 94 of 2600 planned, randomized…"
NCT00588172
withdrawn; "No funding"
NCT00617058
terminated; "Terminated in lieu of similar,competing large, multi-site study."
NCT00672464
withdrawn; "lack of funding"
NCT00682890
terminated; "Lack of recruitment"
NCT00690456
terminated; "Company decision taken in light of demands by certain national health authorities"
recorded 2026-09-01 · last checked 2026-09-04
Q6
Mouse studies of Metformin used 1000 ppm — over how long?
studies of Metformin used the recorded amount. clinicaltrials.gov+jax-mpd-itp · 2026-09-04
22 recorded entries; mouse, human; tablet; also "1000 ppm", "Met: 1000 ppm and Rapa: 14 ppm", "Metformin 500 mg"
Show the evidence
mouse
metformin C2011
1000 ppm
metformin plus rapamycin C2011
Met: 1000 ppm and Rapa: 14 ppm
human
NCT00131664
Metformin 500 mg
NCT00131664
Metformin 850 mg
NCT00145379
Tablet Metformin 500 mg
NCT00159536
tablet; metformin from Weifa 500 mg / tablet
NCT00283816
Metformin Hydrochloride Tablets, 500 mg.
NCT00386100
Metformin 500 mg (ttd)
12 more recorded rows
humanNCT00386100
Metformin 1000 mg (ttd)
humanNCT00386100
Metformin 1500 mg (ttd)
humanNCT00386100
Metformin 2000 mg (ttd)
humanNCT00466622
metformin 500mg tablets from Weifa
humanNCT00648492
Metformin Hydrochloride ER Tablets 500 mg
humanNCT00648492
Glucophage® XR 500 mg
humanNCT00648518
Metformin Hydrochloride ER Tablets 750 mg
humanNCT00648518
Glucophage® XR Tablets 750 mg
humanNCT00649350
Glucophage XR 750 mg
humanNCT00649948
Glucophage XR 500 mg
humanNCT00650234
Glucophage® XR Tablets 500 mg
humanNCT00703508
tablet; Metformin 500 mg tablet
recorded 2026-09-04 · last checked 2026-09-04
Q7
Did Metformin move epigenetic age, and by how much?
epigenetic age: "We aimed to test the efficacy and safety of metformin to improve epigenetic age in older, well-controlled, non-diabetic people living with HIV." Europe PMC · epigenetic clock search · 2026-07-28
8 recorded sentences; 2026, 2022; biomarker
Show the evidence
epigenetic agePMID 42023167
2026; "We aimed to test the efficacy and safety of metformin to improve epigenetic age in older, well-controlled, non-diabetic people living with HIV."
PhenoAgePMID 42023167
2026; "At week 96, the adjusted between-group difference (metformin vs. placebo) for PhenoAge EAA was -1.02 years (95% confidence interval [CI] -5.30 to 3.26; p = 0.627)."
Hannum
2026; "Exogenous compounds showed higher heterogeneity and mixed evidence, including robust null epigenetic findings in some trials (e.g., metformin adjusted ITT differences ranging from −0.91 to +0.82 years across clocks, all p≥0.18) alongside favorable signals in smaller analytic subsets or open-label settings (e.g., bezisterim sub-study with reductions of −3.68 years in SkinBloodAge, −5.00 in Hannum,…"
2026; "Metformin reduced biological age estimated by PC-Horvath2 (−0.40±0.16 per year, p=0.014) and PC-Hannum (−0.33±0.16 per year, p=0.047) clocks."
2026; "Metformin also reduced biological age estimated by the epigenetic clocks PC-Horvath2 and PC-Hannum in peripheral blood."
epigenetic clockPMID 36226195
2022; "However, studies on how metformin affects global epigenetic regulation and its effect on the epigenetic clock in diabetes mellitus (DM) patients are limited."
epigenetic agePMID 36226195
2022; "This study aims to investigate the impact of metformin on the epigenetic age in subjects with type 2 DM. <b>Results:</b> We collected the peripheral blood of the metformin group and the no-metformin group of the 32 DM patients."
HorvathPMID 36226195
2022; "2) We found a strong association between metformin intake and slower epigenetic aging by Horvath's clock and Hannum's clock. <b>Conclusions:</b> Here, we found an association between metformin intake and slower epigenetic aging."
recorded 2026-07-28 · last checked 2026-09-04
Q8
Metformin's half-life is approximately 6.2 hours — which schedules were studied?
approximately 6.2 hours, the half-life Metformin's label states. openfda-label · fb296500-55cb-45ce-be0c-59aa2e3d4624 · 2026-08-27
Show the evidence
half life
approximately 6.2 hours hours; Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours.
tmax
At usual clinical doses and dosing schedules of metformin hydrochloride, steady state plasma concentrations of metformin are reached within 24 to 48 hours and are generally <1 mcg/mL. Effect of food: Food decreases the extent of absorption and slightly delays the absorption of metformin, as shown by approximately a 40% lower mean peak plasma concentration (C max ), a 25% lower area under the…
bioavailability
12.3 Pharmacokinetics Absorption The absolute bioavailability of a metformin hydrochloride 500 mg tablet given under fasting conditions is approximately 50% to 60%.
metabolism
Metabolism Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion.
recorded 2026-08-27 · last checked 2026-09-04
Q9
Which of 24 hour blood glucose levels, a1c at month 6 and a1c at week 24 did Metformin's trials measure?
24 hour blood glucose levels, a1c at month 6 and a1c at week 24 lead 40 outcome terms across Metformin's trials. ClinicalTrials.gov · 2026-09-01
treatment failure, hba1c at week 24, hemoglobin a1c at week 24, a1c at week 24, hba1c and beta cell function after 52 weeks of therapy follow.
Show the evidence
development of diabetes
1
primary major macrovascular events
1
diabetes
1
treatment failure
1
hba1c at week 24
1
hemoglobin a1c at week 24
1
14 more recorded rows
a1c at week 24
1
hba1c
1
beta cell function after 52 weeks of therapy
1
hba1c at 52 weeks
1
flow mediated dilation
1
time to hba1c 8
1
safety
1
effect on hba1c levels
1
haemoglobina1c
1
glycemic control
1
hemoglobin a1c changes from baseline at week 24
1
a1c changes from baseline at week 24 open label cohort
1
hba1c following two years of treatment
1
free testosterone
1
recorded 2026-09-01 · last checked 2026-09-04
Q10
Which of Metformin's 191 ongoing trials reports first?
Overall survival; Observation of CTCAE grade 4 or higher adverse events in six patients; latest 2043-12
Show the evidence
Trial
NCT00268476
"Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy"; n 11992; "Overall survival"; 2030-12
NCT01638676
"A Phase I/II Trial of Vemurafenib and Metformin to Melanoma Patients"; n 55; "Observation of CTCAE grade 4 or higher adverse events in six patients"; 2027-06
NCT01686126
"Improving the Treatment for Women With Early Stage Cancer of the Uterus"; n 165; "Pathological complete response"; 2026-12
NCT01905046
"Metformin Hydrochloride in Preventing Breast Cancer in Patients With Atypical Hyperplasia or In Situ Breast Cancer"; n 86; "Test for the Presence or Absence of Cytological Atypia in Unilateral or Bilateral RPFNA Aspirates After 12 Months."; 2026-11
NCT02087826
"Study of Clinical Response to Acute Metformin By Leveraging Evaluations During a Mixed Meal Tolerance Test for Exploring Glycemia and GeneticS"; n 1017; "Response to the Mixed Meal Tolerance Test"; 2026-12
NCT02336087
"Gemcitabine Hydrochloride, Paclitaxel Albumin-Stabilized Nanoparticle Formulation, Metformin Hydrochloride, and a Standardized Dietary Supplement in Treating Patients With Pancreatic Cancer That Cannot be Removed by Surgery"; n 21; "Feasibility of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement"; 2026-12-09
14 further recorded trials
NCT02365597
"An Efficacy and Safety Study of Erdafitinib (JNJ-42756493) in Participants With Urothelial Cancer"; n 239; "Main Study: Percentage of Participants With Best (Overall) Objective Response"; 2027-03-31
NCT02581137
"Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion"; n 26; "Clinical Response to Metformin Intervention"; 2026-12-19
NCT02647827
"Acupuncture or Metformin for Insulin Resistance in Women With PCOS"; n 303; "Changes from baseline to after 4 months in HOMA-IR [fasting insulin (μU/mL) × fasting glucose (mmol/L)] / 22.5)"; 2026-06
NCT02780024
"Metformin, Neo-adjuvant Temozolomide and Hypo- Accelerated Radiotherapy Followed by Adjuvant TMZ in Patients With GBM"; n 50; "Number of patients completing the study treatment"; 2027-02-28
NCT02879409
"HbA1c Variability in Type II Diabetes"; n 150; "Determination of the variability of HbA1c (by measurement of standard deviation of HbA1c) between the 2 diabetes treatment thresholds"; 2026-10-01
NCT02947503
"Pregnancy Outcomes: Effects of Metformin Study (POEM Study)"; n 500; "GDM Outcome Score (GOS) in Phase A"; 2043-12
NCT02969798
"Pre-diabetes in Subject With Impaired Fasting Glucose (IFG) and Impaired Glucose Tolerance (IGT)"; n 700; "Beta cell function"; 2027-07
NCT03006172
"To Evaluate the Safety, Tolerability, and Pharmacokinetics of Inavolisib Single Agent in Participants With Solid Tumors and in Combination With Endocrine and Targeted Therapies in Participants With Breast Cancer"; n 200; "Stage 1: Percentage of Participants With Dose Limiting Toxicities"; 2026-12-31
NCT03107884
"Role of Metformin on Muscle Health of Older Adults"; n 64; "Muscle size"; 2026-11-01
NCT03311308
"A Trial of Pembrolizumab and Metformin Versus Pembrolizumab Alone in Advanced Melanoma"; n 23; "Ki-67 proliferation index in T cell"; 2029-12-31
NCT03379909
"Phase II Study of Oral Metformin for Intravesical Treatment of Non-muscle-invasive Bladder Cancer"; n 49; "Overall response"; 2029-10-01
NCT03424005
"A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer"; n 1132; "Objective Response Rate (ORR)"; 2030-09-30
NCT03511118
"Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants"; n 1600; "M/P ratio"; 2028-07-31
NCT03603912
"Targeting Risk Interventions and Metformin for Atrial Fibrillation (TRIM-AF)"; n 175; "Change in AF burden"; 2026-12
recorded 2026-09-01 · last checked 2026-09-04
Q11
Which running trial of Metformin could settle insulin sensitivity?
NCT06772857 measures Change in Insulin Resistance Between Different Exercise Modes in Obese Patients, reading out 2025-01-30.
22 open trials; n 3; "Aerobic Versus Resistance Exercises on Insulin Sensitivity in Obese Patients"
Show the evidence
Trial
NCT06772857
"Aerobic Versus Resistance Exercises on Insulin Sensitivity in Obese Patients"; n 3; "Change in Insulin Resistance Between Different Exercise Modes in Obese Patients"; 2025-01-30
NCT05680805
"Metabolic Responses of Metformin and Genetic Polymorphisms of SLC22A1 Gene in PCOS"; n 100; "Homeostasis model assessment of insulin resistance (HOMA-IR)"; 2025-11-30
NCT06826092
"Metformin for the Treatment of mCRC Patients Undergoing FOLFIRI Plus Target Therapy"; n 110; "Disease progression-free survival (PFS)"; 2025-12-31
NCT06889454
"Cardiovascular and Endothelial Markers During OGTT Before and at Six and Twelve Months Post-treatment in Women With PCOS"; n 120; "Τhe change in Global Longitudinal Strain during Oral glucose Tolerance Test"; 2026-02-01
NCT07475546
"Combination Gerotherapeutic Interventions for Healthspan Improvement"; n 30; "Change in cardiorespiratory fitness measured by maximal oxygen uptake (VO₂ max)"; 2026-04
NCT02647827
"Acupuncture or Metformin for Insulin Resistance in Women With PCOS"; n 303; "Changes from baseline to after 4 months in HOMA-IR [fasting insulin (μU/mL) × fasting glucose (mmol/L)] / 22.5)"; 2026-06
14 further recorded trials
NCT07307677
"Melatonin & Metformin on Clinical & Biochemical Parameters in Insulin Resistant PCOS Compared to Metformin"; n 60; "Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)"; 2026-08-10
NCT04925063
"The Effect of Metformin in Patients With Newly Diagnosed mHSPC"; n 266; "Castration-resistant prostate cancer free survival"; 2027-01-31
NCT05893225
"Metformin Add-on Clinical Study in Multiple Sclerosis to Evaluate Brain Remyelination And Neurodegeneration"; n 120; "Change in walking speed"; 2027-02-28
NCT07770711
"Inositol and Metformin Administration in Mediterranean Diet and Low-Carbohydrate Diets in Women With PCOS"; n 90; "Change in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) from Baseline to 2 Months"; 2027-06
NCT07293325
"Semaglutide and Tirzepatide for Genetic Aging Delay in Adults With Obesity"; n 66; "Change in DNA methylation-based biological age measured by iWatchAge"; 2027-06-02
NCT04758000
"Metformin as Maintenance Therapy in Patients With Bone Sarcoma and High Risk of Relapse"; n 67; "Event Free Survival"; 2027-07
NCT05445791
"Metformin Plus Tyrosine Kinase Inhibitors for Treatment of Patients With Non-small Cell Lung Cancer With EGFR Mutations"; n 312; "Progression-free survival"; 2027-07-14
NCT04945148
"Oxidative Phosphorylation Targeting In Malignant Glioma Using Metformin Plus Radiotherapy Temozolomide"; n 640; "Assessement of Progression Free Survival (PFS) of patients with newly-diagnosed IDH wild-type OXPHOS + GBM (either with or without FGFR3-TACC3 gene fusion) treated with RT plus TMZ combined with metformin"; 2028-05
NCT06537843
"Safety and Efficacy of Venetoclax, Cytarabine and Metformin (VenCM) for Relapsed-Refractory and Induction-Ineligible Acute Myeloid Leukemia"; n 100; "Overall Survival (OS)"; 2028-07-01
NCT03925714
"Impact of P53 and SIRT1 in Type 2 Diabetes"; n 90; "Number of patients with improved insulin resistance"; 2028-12
NCT04530058
"The Effects of Metformin on Morbidity and Mortality in Elderly Patients"; n 250; "Record mortality"; 2029-03
NCT06829238
"Assessment of Metformin for Restoration of Immune Homeostasis in HIV+ and HIV- Individuals With a History of Injection Drug Use"; n 100; "Change in Serum C-reactive Protein (CRP)"; 2029-11-30
NCT06975111
"Focusing on the Menopausal Transition to Improve Mid-Life Women's Health"; n 200; "Epigenetic aging measurements of "PhenoAge""; 2030-10-01
NCT00268476
"Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy"; n 11992; "Overall survival"; 2030-12
Q12
Which 559 trials of Metformin posted no result?
Posted no result
559 of 559 completed trials
Registrations
NCT00004992, NCT01511198, NCT02526615, NCT00864669, NCT00865839 and NCT00358124, and 553 more
Completion dates
oldest 2001-04; newest 2024-07-31
Show the evidence
Trial
NCT00004992
2001-04
NCT01511198
2001-10
NCT02526615
2001-12
NCT00864669
2002-03
NCT00865839
2002-03
NCT00358124
2002-06
14 further recorded trials
NCT00648492
2002-11
NCT00650312
2002-11
NCT00864734
2002-11
NCT00865241
2002-11
NCT01511172
2002-12
NCT02280057
2002-12
NCT01720290
2003-02-25
NCT00118950
2003-03
NCT03259919
2003-03
NCT00413179
2003-04
NCT00865072
2003-08
NCT00865852
2003-08
NCT00035542
2003-10
NCT00568984
2003-11-10
Q13
At the median, Metformin's trials enrolled 72.5 people — anything larger?
Median enrolment
72.5
Largest enrolment
1499650
Registered trials counted
1682
Q14
What do 28218 spontaneous reports say about Metformin — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Metformin appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 28218 reaction mentions were counted: lactic acidosis 7697; acute kidney injury 5387; hypoglycaemia 2567; diarrhoea 2429. open-targets-adr · CHEMBL1431 · 2026-06-24
Show the evidence
lactic acidosis
7697
acute kidney injury
5387
hypoglycaemia
2567
diarrhoea
2429
metabolic acidosis
2428
vomiting
1964
4 more recorded rows
toxicity to various agents
1927
hypotension
1394
hyperkalaemia
1327
renal failure
1098
recorded 2026-06-24 · last checked 2026-09-04
Q15
Was Metformin studied with fasting and exercise?
fasting and exercise are named in Metformin's label sentences: "Increased metabolic insulin sensitivity related to reductions in fasting glucose (r = -0.41, p = 0.025), VO<sub>2</sub>max (r = 0.55, p = 0.002), fasting leptin (r = -0.54, p = 0.01), and weight loss (r = -0.60, p < 0.001) after exercise and placebo, but not exercise and metformin." openfda-label+europepmc · 2026-08-26
2 recorded statements; fasting, exercise
Show the evidence
fasting
Increased metabolic insulin sensitivity related to reductions in fasting glucose (r = -0.41, p = 0.025), VO<sub>2</sub>max (r = 0.55, p = 0.002), fasting leptin (r = -0.54, p = 0.01), and weight loss (r = -0.60, p < 0.001) after exercise and placebo, but not exercise and metformin.
exercise
In a double-blind, placebo controlled trial, participants were randomized to low intensity exercise plus placebo (∼55% VO<sub>2</sub>max 5 days/week, LoEx+PL, n = 22) or metformin (2000 mg/day, LoEx+Met, n = 21) and high intensity exercise plus placebo (∼85% VO<sub>2</sub>max 5 days/week, HiEx+PL, n = 24) or metformin (HiEx+Met, n = 24) for 16 weeks.
recorded 2026-08-26 · last checked 2026-09-04
Q16
What is recorded about Metformin and sirtuin?
"Blocking SIRT1 with EX527 or SIRT1 siRNA weakened UPRmt activation and largely reversed the mitochondrial, cellular, and matrix effects of metformin." — where Metformin and sirtuin appear together. Europe PMC · pathway abstract search · 2026-09-02
"Blocking SIRT1 with EX527 or SIRT1 siRNA weakened UPRmt activation and largely reversed the mitochondrial, cellular, and matrix effects of metformin."
mTORPMID 42163729
"Additionally, adenosine 5'-monophosphate-activated protein kinase (AMPK) expression was altered to evaluate the involvement of AMPK/ mammalian target of rapamycin (mTOR)/ phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) signaling in the effects of metformin."
AMPK
PMID 42163729
"Additionally, adenosine 5'-monophosphate-activated protein kinase (AMPK) expression was altered to evaluate the involvement of AMPK/ mammalian target of rapamycin (mTOR)/ phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) signaling in the effects of metformin."
PMID 42163729
"Our results revealed that metformin promoted osteogenic differentiation, enhanced autophagy, and activated the AMPK pathway."
autophagyPMID 42163729
"Our results revealed that metformin promoted osteogenic differentiation, enhanced autophagy, and activated the AMPK pathway."
mTORPMID 42163729
"Treatment with 3-MA inhibited the effects of metformin on osteogenic differentiation, autophagy, and AMPK/mTOR/p70S6K signaling in osteoblasts."
AMPKPMID 42163729
"Treatment with 3-MA inhibited the effects of metformin on osteogenic differentiation, autophagy, and AMPK/mTOR/p70S6K signaling in osteoblasts."
autophagyPMID 42163729
"Treatment with 3-MA inhibited the effects of metformin on osteogenic differentiation, autophagy, and AMPK/mTOR/p70S6K signaling in osteoblasts."
mTORPMID 42163729
"Our findings revealed that AMPK/mTOR/p70S6K signaling is involved in metformin- regulated osteogenic differentiation through the induction of autophagy."
autophagyPMID 42163729
"Our findings revealed that AMPK/mTOR/p70S6K signaling is involved in metformin- regulated osteogenic differentiation through the induction of autophagy."
1 more recorded row
senolyticPMID 42534639
"Comparative consideration is also given to established aging-relevant candidates, including metformin, rapamycin, resveratrol, GLP-1 receptor agonists, NAD<sup>+</sup> modulators, and senolytic strategies, in order to contextualize the potential relevance and limitations of metabolic-vascular pathway modulation in aging research."
NAD+
PMID 42534639
"Comparative consideration is also given to established aging-relevant candidates, including metformin, rapamycin, resveratrol, GLP-1 receptor agonists, NAD<sup>+</sup> modulators, and senolytic strategies, in order to contextualize the potential relevance and limitations of metabolic-vascular pathway modulation in aging research."
PMID 42414524
"Metformin, as mitochondrial complex I inhibitor, increased the cellular NADH/NAD+ ratio."
sirtuin
"Mechanistically, metformin activated AMPK/SIRT1 to upregulate PGC-1α; AMPK or SIRT1 inhibition blocked this cascade and reversed protection."
"Metformin restrains AAA by restoring VSMC mitochondrial homeostasis via the AMPK/SIRT1→PGC-1α axis, positioning PGC-1α as a non-redundant, cell-autonomous guardian against vascular degeneration."
NAD+PMID 42228790
"Metformin enhances antioxidant defenses by activating Nrf2 through Kelch-like ECH-associated protein 1 degradation and increasing cytoprotective mediators such as heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1."
senolyticPMID 41751214
"Compounds such as metformin, rapamycin, anti-inflammatories, GLP-1 agonists, senolytics, spermidine, SGLT2 inhibitors, and sirtuin activators have shown lifespan extension in animal models."
recorded 2026-09-02 · last checked 2026-09-04
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