This page shows what was measured, who it was measured in, and what that does not settle.
What Metformin Hydrochloride, Sitagliptin does in the body
RNAWiki has not recorded what this substance changes in the body.
What happened in people
RNAWiki has not yet published a reviewed conclusion for this use.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
No reviewed claim names a result for any goal on this record.
No source is stored against this line.
The limit that matters most
Not recorded.
Where it acts
Not recorded.
Kind of result
No result is published, so no kind of result applies yet
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
The label declares 2 active ingredients: sitagliptin and metformin hydrochloride.
Recorded product composition
Where each sentence above came from
No plain explanation of what this changes is stored.
No recorded use is stored in reader language.
No statement of the main limit is recorded.
The four opening statements run to 26 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.
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.
Receptor
A receptor is a part of a cell that a signal fits into.
A picture of it, and where the picture fails
A receptor is like a lock waiting for one key.
Where that stops being true. A lock either opens or does not. A receptor can be half-triggered, or worn out.
What people get wrong. Fitting a receptor is read as causing a benefit. It causes a step, and nothing more.
A protein that binds a specific ligand and converts that binding into a cellular response.
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 20 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 moved3 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.
Body weight
∅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 moved2 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
hba1c; hba1c level; fasting insulin
Body weight
body weight and fructosamine levels during ramadan fasting; body weight
Fertility and sexual health
total 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
3 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.
Time to First Occurrence of MACE (Composite Endpoint of Major Adverse Cardiovascular Events [Cardiovascular Death, Non-fatal Myocardial Infarction or Non-fatal Stroke]) (On-Treatment + 365-day Approach) (Overall Cardiovascular Study)
✗ The study did not show it
Who was studied
NCT01986881
How many people
8246
Study design
Phase 3
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
Result not recorded on this page
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. 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.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
Europe PMC · a recorded source, not a stored snapshot
Time to HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication
✗ The study did not show it
Who was studied
NCT01794143
How many people
7850
Study design
Phase 3
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Result not recorded on this page
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. 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.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
Europe PMC · a recorded source, not a stored snapshot
Change From Phase 2 Baseline to Week 44 in Hemoglobin A1c (HbA1c) Levels (Phase 2)
✗ The study did not show it
Who was studied
NCT01709305
How many people
5570
Study design
Phase 4
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Result not recorded on this page
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. 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.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
Europe PMC · a recorded source, not a stored snapshot
Changes From Baseline in Glycosylated Haemoglobin (HbA1c) (%) After 52 Weeks of Treatment
✗ The study did not show it
Who was studied
NCT01289990
How many people
2705
Study design
Phase 3
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Result not recorded on this page
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. 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.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
Europe PMC · a recorded source, not a stored snapshot
To evaluate the efficacy of vildagliptin as add-on therapy to metformin in patients with T2DM by assessing changes in HbA1c with vildagliptin added to metformin to that of placebo added to metformin after 24 weeks of treatment
✗ The study did not show it
Who was studied
NCT00860288
How many people
1988
Study design
Phase 2/Phase 3
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Result not recorded on this page
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. 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.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
Europe PMC · a recorded source, not a stored snapshot
Change From Baseline in Hemoglobin A1C (A1C) at Week 24
✗ The study did not show it
Who was studied
NCT00722371
How many people
1615
Study design
Phase 3
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Result not recorded on this page
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. 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.
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
openFDA Drugs@FDA · a recorded source, not a stored snapshot
openFDA NDC Directory · a recorded source, not a stored snapshot
Europe PMC · 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 eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.0 registered measures of this kind. 1 written-up study 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.7 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 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.
hemoglobin a1c at week 18
hba1c
body weight and fructosamine levels during ramadan fasting
hba1c level
body weight
fasting insulin
hemoglobin a1c
Meaningful
Things that change how a life goes, not only a number.
No registered study measured anything of this kind.
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 (13)
a1c at week 32
any adverse experience
medical resource utilization
beta cell function
an adverse event
concomitant conditions
nerve conduction velocity in vep
total testosterone
follicle stimulating hormone
ratios of geometrical mean
mace
modified mace
hs crp
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
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
No description of who was studied is recorded.
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.
Where the result stopped carrying
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 2 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
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No form or route is recorded.
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
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
Nothing is recorded about product quality.
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∅Nothing found in the sources checked
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.
∅Nothing found in the sources checked
No harm is recorded against this substance in the sources RNAWiki checked. Finding nothing is not the same as showing there is nothing.
The sources listed were searched and held nothing. That is not the same as nothing existing.
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 Hydrochloride, Sitagliptin 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
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
The exact form studied is not recorded.
No source is stored against this line.
What is sold
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
Nothing further is recorded about which forms are sold.
No source is stored against this line.
What is recorded as being sold
Sitagliptin and Metformin Hydrochloride is oral at 3 DOSAGE FORMS AND STRENGTHS Tablets: Sitagliptin 100 mg and metformin hydrochloride 1,000 mg extended-release tablets are reddish brown to brown colored, oval shaped, film-coated tablets debossed with "1806" on one sid…, recorded as fda label in effect 2024-08-31 in the United States.
US prescribing information · d3a728a0-decb-4340-8ee4-c5e27c13eb19 · read 2026-08-30
Recorded price in US: 1.75986–1.92131 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 8 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.
This order is fixed in code and does not count clicks or time on the page.
What is not here
6 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.
The path through the body — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
Claims that go past the evidence — 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.
Recorded evidence blocks (12)
Q2
What did Metformin Hydrochloride, Sitagliptin's largest trial (781430 people) and its longest (7.8 years) measure?
781430 people in Metformin Hydrochloride, Sitagliptin's largest registered study, 7.8 years in its longest registered window, measuring The area under the plasma concentration-time curve (AUC) after administration of sitagliptin/metformin (50/500; 50/850; 50/1000 mg/mg) FDC tablet and co-administration of corresponding doses of… ClinicalTrials.gov · 2026-09-01
7 phase4, 6 na, 6 phase3, 5 na or unstated, 5 phase1, 3 phase2; NCT05480007; 2018-12-01; no ageing endpoint recorded. Last human test completed 2025, NCT07763964.
Interpretation These counts include studies where Metformin Hydrochloride, Sitagliptin 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
phase4
7
na
6
phase3
6
na or unstated
5
phase1
5
phase2
3
1 more recorded row
Last recorded human testNCT07763964
2025-12-19
recorded 2026-09-01 · last checked 2026-09-04
Q3
From yeast to human: where has Metformin Hydrochloride, Sitagliptin shown lifespan?
C. elegans: lifespan, Drosophila: lifespan, NHP: mechanism-only, yeast: lifespan, mouse: lifespan, rat: lifespan, dog: lifespan and human: biomarker (30): the rungs where Metformin Hydrochloride, Sitagliptin has a recorded finding. Europe PMC and ClinicalTrials.gov · organism ladder · 2026-09-01
The area under the plasma concentration-time curve (AUC) after administration of sitagliptin/metformin (50/500; 50/850; 50/1000 mg/mg) FDC tablet and… — 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
humanNCT00961480
biomarker; The area under the plasma concentration-time curve (AUC) after administration of sitagliptin/metformin (50/500; 50/850; 50/1000 mg/mg) FDC tablet and co-administration of corresponding doses of sitagliptin and metformin as individual…; 30
recorded 2026-09-01 · last checked 2026-09-04
Q4
Why did Metformin Hydrochloride, Sitagliptin's trial NCT01357148 stop?
"Completion of MK-0431A-235 was rendered unnecessary, as the local oversight authority accepted in its stead the results of another study \[MK-0431-234\]."; 1 of 30 registered studies
Show the evidence
TrialNCT01357148
terminated; "Completion of MK-0431A-235 was rendered unnecessary, as the local oversight authority accepted in its stead the results of another study \[MK-0431-234\]."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Metformin Hydrochloride, Sitagliptin used sitagliptin/metformin 50 mg/500 mg tablet — over how long?
Did Metformin Hydrochloride, Sitagliptin 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
Q7
Which of a1c at week 32, an adverse event and any adverse experience did Metformin Hydrochloride, Sitagliptin's trials measure?
a1c at week 32, an adverse event and any adverse experience lead 20 outcome terms across Metformin Hydrochloride, Sitagliptin's trials. ClinicalTrials.gov · 2026-09-01
Interpretation any adverse experience, medical resource utilization, beta cell function, an adverse event, concomitant conditions and body weight and fructosamine levels during ramadan fasting follow.
Show the evidence
hemoglobin a1c at week 18
1
a1c at week 32
1
hba1c
1
any adverse experience
1
medical resource utilization
1
beta cell function
1
14 more recorded rows
an adverse event
1
concomitant conditions
1
body weight and fructosamine levels during ramadan fasting
1
nerve conduction velocity in vep
1
hba1c level
1
body weight
1
fasting insulin
1
total testosterone
1
follicle stimulating hormone
1
ratios of geometrical mean
1
mace
1
modified mace
1
hs crp
1
hemoglobin a1c
1
recorded 2026-09-01 · last checked 2026-09-04
Q8
What will the one ongoing trial of Metformin Hydrochloride, Sitagliptin report, and when?
1 registered trial of Metformin Hydrochloride, Sitagliptin is open; earliest completion 2027-09-30. ClinicalTrials.gov · 2026-09-01
Interpretation MACE
Show the evidence
TrialNCT05220917
"Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study"; n 781430; "MACE"; 2027-09-30
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which 12 trials of Metformin Hydrochloride, Sitagliptin posted no result?
Posted no result
12 of 12 completed trials
Registrations
NCT00961857, NCT00961480, NCT01332370, NCT00969566, NCT01624116 and NCT01718093, and 6 more
Completion dates
oldest 2006-01-01; newest 2023-02-01
Show the evidence
Trial
NCT00961857
2006-01-01
NCT00961480
2007-11
NCT01332370
2010-12
NCT00969566
2011-07
NCT01624116
2011-09
NCT01718093
2015-12
6 further recorded trials
NCT02941445
2016-08
NCT04877106
2018-07-31
NCT01336322
2018-12
NCT05480007
2018-12-01
NCT05167513
2022-04-28
NCT05822674
2023-02-01
Q10
At the median, Metformin Hydrochloride, Sitagliptin's trials enrolled 63 people — anything larger?
Median enrolment
63
Largest enrolment
781430
Registered trials counted
30
Q11
What do 28218 spontaneous reports say about Metformin Hydrochloride, Sitagliptin — 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 Hydrochloride, Sitagliptin 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
Q12
Was Metformin Hydrochloride, Sitagliptin studied with fasting and exercise?
fasting and exercise are named in Metformin Hydrochloride, Sitagliptin'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 · 2026-03-01
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 2026-03-01 · last checked 2026-09-04
Q13
What is recorded about Metformin Hydrochloride, Sitagliptin 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 Hydrochloride, Sitagliptin 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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