This page shows what was measured, who it was measured in, and what that does not settle.
What Diclofenac does in the body
Diclofenac blocks the two enzymes that build prostaglandins, the messengers that make an inflamed joint hurt and swell.
What separates it from ibuprofen is which of the two enzymes it prefers: diclofenac leans heavily toward COX-2, the form that appears during inflammation, in about the same ratio as the drugs that were designed and marketed as selective COX-2 inhibitors. That bias buys the best pain relief of any NSAID in arthritis. It also tips the balance in blood vessels — the same shift that made the coxibs raise heart attack risk — and the measured cardiovascular numbers for diclofenac sit alongside theirs rather than alongside ibuprofen’s.
Why people take it. Arthritis pain and inflammation
What happened in people
Osteoarthritis pain effect size -0.57 at 150 mg/day, the largest of any maximally approved NSAID dose across 76 trials and 58,451 patients
✎ 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.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
Approved in the United States in 1988 under NDA 019201; the topical gel switched to over-the-counter status under NDA 022122, while the tablet did not
Where it acts
The cyclooxygenase channel, preferentially COX-2 in inflamed synovium and vascular endothelium; the topical formulation acts in the joint tissue under the skin it is applied to
Kind of result
Symptoms and quality of life
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 supplement label database classes it as other, under the name Diclofenac.
Its recorded molecular formula is C14H10Cl2NNaO2, weighing 318.14.
US prescribing information · 0379c918-1717-40ab-81cc-268116950fd5 · read 2026-08-30
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 133 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.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
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.
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
Pain
∅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.
…Waiting for a reviewer10 registered symptom measure.
∅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
Pain
pain; rated visual analogue scale pain intensity assessment; global pain intensity as assessed by visual analog scale; assessment of pain visual analogue scale; s assessment of ankle pain vas; pain on movement; pain intensity; pain vas
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.
… Waiting for a reviewer
10 registered symptom measure.
— Not recorded
Harms were not a registered measure for this goal.
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.
Major vascular events — non-fatal myocardial infarction, non-fatal stroke or vascular death — with major coronary events, stroke, mortality, heart failure and upper gastrointestinal complications as further outcomes
✗ The study did not show it
Who was studied
CNT Collaboration pooled randomised trials (Lancet 2013;382:769-779)
How many people
124513
Study design
Individual-participant meta-analysis of 280 placebo-controlled and 474 active-comparator randomised trials
Compared against
A dummy treatment
Kind of result
Living longer, or avoiding a major event
What was found
Diclofenac major vascular events rate ratio 1.41 (95% CI 1.12 to 1.78), p=0.0036; major coronary events 1.70 (1.19 to 2.41), p=0.0032; vascular death 1.65 (0.95 to 2.85), p=0.0187; upper gastrointestinal complications 1.89 (1.16 to 3.09), p=0.0106
Repeated elsewhere
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. Heart failure risk was roughly doubled by all NSAID regimens in the analysis. The proportional effects on major vascular events were independent of baseline characteristics including vascular risk, which means a low-risk patient gets the same proportional increase on a smaller base.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral delayed-release tablets (diclofenac sodium) and immediate-release tablets (diclofenac potassium), extended-release tablets, capsules, topical gel and solution, transdermal patch, ophthalmic solution and injection
Interval reported. 95% CI 1
Written into the record, not signed off as a reviewed claim.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
Intention-to-treat incidence rate ratio of major adverse cardiovascular events within 30 days of initiation
✗ The study did not show it
Who was studied
Danish nationwide emulated trial series (BMJ 2018;362:k3426)
How many people
1370832
Study design
Series of 252 nationwide cohort studies with emulated-trial design, 1996-2016
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
1.5 (95% CI 1.4 to 1.7) against non-initiators, 1.2 (1.1 to 1.3) against paracetamol and against ibuprofen initiators, 1.3 (1.1 to 1.5) against naproxen initiators; myocardial infarction 1.9 (1.6 to 2.2), cardiac death 1.7 (1.4 to 2.1)
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. This is observational and cannot exclude confounding by indication despite propensity matching and the deliberate restriction to a low-baseline-risk population. It exists because a randomised cardiovascular outcome trial of diclofenac is now regarded as unethical to run.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral delayed-release tablets (diclofenac sodium) and immediate-release tablets (diclofenac potassium), extended-release tablets, capsules, topical gel and solution, transdermal patch, ophthalmic solution and injection
Interval reported. 95% CI 1
Written into the record, not signed off as a reviewed claim.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
Osteoarthritis pain, with physical function as secondary outcome
✓ The study showed what it set out to show
Who was studied
Network meta-analysis of NSAIDs in knee and hip osteoarthritis (Lancet 2017;390:e21-e33)
How many people
58451
Study design
Bayesian network meta-analysis of 76 randomised trials with at least 100 patients per group
Compared against
Not recorded for this study
Kind of result
What a body can do day to day
What was found
Diclofenac 150 mg/day effect size -0.57 (95% credible interval -0.69 to -0.45) against placebo, 100% probability of exceeding the prespecified minimum clinically important difference of -0.37 and the highest probability of being the best maximally approved dose
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. The comparison is of efficacy only. The authors explicitly direct that the result be considered together with all known safety information, and the same analysis includes rofecoxib — withdrawn worldwide — among the preparations exceeding the clinical relevance threshold.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral delayed-release tablets (diclofenac sodium) and immediate-release tablets (diclofenac potassium), extended-release tablets, capsules, topical gel and solution, transdermal patch, ophthalmic solution and injection
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
RNAWiki holds 3 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 lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.11 registered measures of this kind.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.2 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 Mouse. 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.
Start
Diclofenac
What a person takes: Oral delayed-release tablets (diclofenac sodium) and immediate-release tablets (diclofenac potassium), extended-release tablets, capsules, topical gel and solution, transdermal patch, ophthalmic solution and injection.
The measurement behind this step
The sodium salt is enterically coated so that release occurs beyond the stomach, which delays onset; the potassium salt is used where faster absorption is wanted, as in acute pain and dysmenorrhoea. Plasma protein binding exceeds 99% and metabolism is hepatic, principally by CYP2C9 with subsequent glucuronidation. The topical route achieves therapeutic tissue concentrations in superficial joints at plasma concentrations far below those from oral dosing, which is the pharmacological basis for its separate regulatory treatment.
Getting in
Two chlorines twist the molecule, and the twist picks the enzyme
Diclofenac carries two chlorine atoms that force its two rings out of alignment. That shape fits the roomier inflammation enzyme better than the tighter housekeeping one — which is the whole of its character.
──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
2-(2,6-dichloroanilino)phenylacetic acid. The ortho-dichloro substitution enforces a dihedral twist that favours the larger COX-2 active site. In whole-blood assays the resulting COX-2 selectivity ratio falls in the same range as drugs designed and marketed as selective COX-2 inhibitors. Plasma protein binding exceeds 99%.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
In the joint, that preference is exactly what you want
The enzyme that appears during inflammation is the one doing the damage in an arthritic joint. Blocking it preferentially is why diclofenac outperformed every other anti-inflammatory in the largest comparison of arthritis pain.
──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
COX-2 is induced in inflamed synovium and is the dominant source of prostaglandin E2 there. Network meta-analysis of 76 trials and 58,451 patients: diclofenac 150 mg/day effect size -0.57 (95% credible interval -0.69 to -0.45), the largest of any maximally approved NSAID dose, with 100% probability of exceeding the minimum clinically important difference.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
And it spares the stomach more than ibuprofen or naproxen
The housekeeping enzyme that protects the stomach lining is left relatively alone, so serious gastric complications are lower than with the non-selective drugs.
╌╌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
Upper gastrointestinal complications against placebo: diclofenac 1.89 (95% CI 1.16 to 3.09), against ibuprofen 3.97 (2.22 to 7.10) and naproxen 4.22 (2.71 to 6.56). The same selectivity that produces the arthritis efficacy produces the gastric advantage.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
In blood vessels the same preference is the problem
The vessel wall makes a substance that keeps platelets calm using the inflammation enzyme; platelets make the opposing clotting signal using the housekeeping one. Blocking one and not the other tips the balance toward clotting.
╌╌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
Endothelial prostacyclin is largely COX-2-derived; platelet thromboxane A2 is COX-1-derived. Preferential COX-2 inhibition without matching platelet COX-1 inhibition shifts the prostacyclin-thromboxane balance — the mechanism proposed for the coxib cardiovascular signal, and the one diclofenac shares. Major vascular events rate ratio 1.41 (1.12 to 1.78) against placebo.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
The signal appears within a month, and at low doses
This is not a slow accumulation over years. In 1.37 million people starting diclofenac, the excess in heart attacks, strokes, heart failure and cardiac deaths was measurable in the first thirty days, including in those on small doses.
╌╌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
Danish emulated-trial series: incidence rate ratio at 30 days 1.5 (1.4 to 1.7) against non-initiators, with myocardial infarction 1.9 (1.6 to 2.2), heart failure 1.7 (1.4 to 2.0), ischaemic stroke 1.6 (1.3 to 2.0) and cardiac death 1.7 (1.4 to 2.1), and the increase present for low doses as well.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
What was measured, and what nobody will now measure
Measured: the best arthritis pain relief of the class, and a cardiovascular risk profile alongside a drug that was withdrawn from every market. Not measured, and now unlikely ever to be: a randomised cardiovascular outcome trial of diclofenac.
──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
Celecoxib has PRECISION, 24,081 patients. Diclofenac has no equivalent. The European Society of Cardiology working group position, cited by the Danish investigators as their reason for an emulated-trial design, is that current concerns about diclofenac’s cardiovascular risks now make such a trial unethical to conduct.
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · 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 6 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.
global pain intensity as assessed by visual analog scale
assessment of pain visual analogue scale
s assessment of ankle pain vas
pain on movement
swiss spinal stenosis questionnaire
pain intensity
pain vas
spontaneous pharyngeal pain
and 1 more.
Measured
Things only a test, a scale or a device shows.
area under the concentration time curve
auc of dabigatran in plasma
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 (27)
physical function
incidence of treatment emergent adverse events
post ercp pancreatitis
acute pseudophakic cystoid macular edema
bioequivalence based on auc and cmax
intraocular pressure change
probe substrate pk parameters auctlast
probe substrate pk parameters aucinf
probe substrate pk parameters tmax
probe substrate pk parameters hl
probe substrate pk parameters cl/f
probe substrate pk parameters vz/f
1st peak rms knee index
incidence of post ercp pancreatitis
respiratory insufficiency
auc ss on day 4
cmax ss
cmax
auc0 infinity
auer ss
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
People similar to this profile were included.
People with osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, and enormous numbers of people worldwide buying it over the counter. It is contraindicated in the setting of coronary artery bypass graft surgery and, in several jurisdictions, in established ischaemic heart disease, cerebrovascular disease, peripheral arterial disease and moderate-to-severe heart failure.
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 in pediatric patients have not been established.”
US prescribing information · 0379c918-1717-40ab-81cc-268116950fd5 · read 2026-08-30
On older people, the label states: “Elderly patients, compared to younger patients, are a greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions.”
US prescribing information · 0379c918-1717-40ab-81cc-268116950fd5 · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary Use of NSAIDs, including diclofenac sodium, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.”
US prescribing information · 0379c918-1717-40ab-81cc-268116950fd5 · read 2026-08-30
On people who are breastfeeding, the label states: “Risk Summary Based on available data, diclofenac may be present in human milk.”
US prescribing information · 0379c918-1717-40ab-81cc-268116950fd5 · read 2026-08-30
Where the result stopped carrying
No randomised cardiovascular outcome trial of diclofenac exists, and the European Society of Cardiology position is that one would now be unethical to conduct
The published recommendation that diclofenac be removed from essential medicines lists has largely not been acted on; it was on 74 national lists as of 2013
Veterinary use was banned across South Asian countries only after three vulture species had been driven to critically endangered status
Every component of the cardiovascular composite moved against diclofenac in the 30-day analysis, including atrial fibrillation and heart failure, not only infarction
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 change is too small to feel
A real change can still sit below what a person notices.
On this record: Approved in the United States in 1988 under NDA 019201; the topical gel switched to over-the-counter status under NDA 022122, while the tablet did not
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 (8)
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.
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 delayed-release tablets (diclofenac sodium) and immediate-release tablets (diclofenac potassium), extended-release tablets, capsules, topical gel and solution, transdermal patch, ophthalmic solution and injection
✎ 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: S3, S6.
No source is stored against this line.
What is in the pack
The sodium salt is enterically coated so that release occurs beyond the stomach, which delays onset; the potassium salt is used where faster absorption is wanted, as in acute pain and dysmenorrhoea.
✎ 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. The rest of the recorded wording: Plasma protein binding exceeds 99% and metabolism is hepatic, principally by CYP2C9 with subsequent glucuronidation. The topical route achieves therapeutic tissue concentrations in superficial joints at plasma concentrations far below those from oral dosing, which is the pharmacological basis for its separate regulatory treatment.
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
Boxed warning for cardiovascular thrombotic events including fatal myocardial infarction and stroke, and for gastrointestinal bleeding, ulceration and perforation. Contraindicated in the setting of coronary artery bypass graft surgery, and in several European jurisdictions additionally in established ischaemic heart disease, cerebrovascular disease, peripheral arterial disease and moderate-to-severe heart failure. Diclofenac carries a higher rate of transaminase elevation than most NSAIDs and labels direct liver monitoring. Renal effects follow the class pattern and are amplified by volume depletion, diuretics, ACE inhibitors and angiotensin receptor blockers.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Where this came from
Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analys… · a recorded source, not a stored snapshot
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.
Diclofenac appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 18452 reaction mentions were counted. One report can name several reactions.
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 delayed-release tablets (diclofenac sodium) and immediate-release tablets (diclofenac potassium), extended-release tablets, capsules, topical gel and solution, transdermal patch, ophthalmic solution and injection
✎ 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
Plasma protein binding exceeds 99% and metabolism is hepatic, principally by CYP2C9 with subsequent glucuronidation. The topical route achieves therapeutic tissue concentrations in superficial joints at plasma concentrations far below those from oral dosing, which is the pharmacological basis for its separate regulatory treatment.
✎ 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
501 products list this as an active ingredient in the United States drug directory. 470 of them contain it and nothing else.
FDA National Drug Code directory · 71610-068 · read 2026-08-29
They are sold as capsule, capsule, liquid filled, gel, ointment, patch and powder, taken cutaneous, ophthalmic, oral and topical.
FDA National Drug Code directory · 71610-068 · read 2026-08-29
The regulator's established pharmacologic class for it is anti-inflammatory agents, cyclooxygenase inhibitors [moa] and decreased prostaglandin production [pe].
FDA National Drug Code directory · 71610-068 · read 2026-08-29
420 published labels name it as an active ingredient. 398 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 84978746-4ab5-456d-af63-5c86ab0a05f5 · read 2026-08-29
Those labels are classed as human otc drug and human prescription drug.
US prescribing information · 84978746-4ab5-456d-af63-5c86ab0a05f5 · read 2026-08-29
14 marketed supplement labels list this ingredient, classed as botanical, non-nutrient/non-botanical, other combinations and other.
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.
Diclofenac Sodium is topical gel, 1% at 1% (diclofenac sodium topical gel), recorded as over-the-counter topical product; fda label in effect 2024-07-29 in the United States.
US prescribing information · 005299ac-b6de-511f-e063-6294a90a29e0 · read 2026-08-27
Recorded price in US: 0.08287–0.39066 USD per one gram, across 24 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: 0.13522–1.799 USD per one millilitre, across 11 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: 2.69509 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, across 6 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.
Evidence on this page does not automatically apply to this one.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Diclofenac studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That "traditional NSAID" describes diclofenac’s pharmacology — its whole-blood COX-2 selectivity sits with the drugs marketed as selective
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the risk is confined to high doses or long courses, when the 30-day analysis found it at low doses within a month
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That over-the-counter availability in much of the world reflects a favourable risk assessment rather than historical inertia
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That efficacy rankings settle the question of which NSAID to use, when the most effective preparation list in the network analysis includes a drug withdrawn worldwide
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Diclofenac are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
In randomised trials it behaves like a coxib, because chemically it is one
In plain words
Diclofenac is filed as a traditional anti-inflammatory, alongside ibuprofen and naproxen. In the pooled randomised evidence its heart numbers sit with the selective COX-2 drugs, not with the traditional ones — and its enzyme preference explains why.
What was measured
Rate ratios for major vascular events, major coronary events, vascular death and upper gastrointestinal complications against placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
In the CNT individual-participant meta-analysis of 280 placebo-controlled trials, major vascular events rose by about a third with a coxib (rate ratio 1.37, 95% CI 1.14 to 1.66, p=0.0009) and by a very similar amount with diclofenac (1.41, 1.12 to 1.78, p=0.0036). Major coronary events rose 1.76-fold (1.31 to 2.37) with coxibs and 1.70-fold (1.19 to 2.41, p=0.0032) with diclofenac. Vascular death rose significantly with coxibs (1.58, 99% CI 1.00 to 2.49) and with diclofenac (1.65, 0.95 to 2.85, p=0.0187). The collaboration’s own interpretation opens: the vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs. On the other side of the ledger diclofenac was among the gentler drugs on the stomach — upper gastrointestinal complications 1.89 (1.16 to 3.09) against ibuprofen’s 3.97 and naproxen’s 4.22 — which is the same COX-2 preference showing up as a benefit. The classification "traditional NSAID" is a regulatory and historical category, not a pharmacological one.
Written into the record, not signed off as a reviewed claim
A 1.37-million-person emulated trial: risk within 30 days, and at low doses
In plain words
Danish registry data were used to reconstruct 252 trial-like comparisons among 1.37 million people starting diclofenac. Major cardiovascular events were 50% more common within thirty days than in people starting nothing — and 20% more common than in people starting ibuprofen or paracetamol.
What was measured
Incidence rate ratio for major adverse cardiovascular events and upper gastrointestinal bleeding within 30 days of initiation, against non-initiation and against three active comparators
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The study included 1,370,832 diclofenac initiators, 3,878,454 ibuprofen initiators, 291,490 naproxen initiators, 764,781 propensity-matched paracetamol initiators and 1,303,209 propensity-matched non-initiators, all adults without malignancy, schizophrenia, dementia, or cardiovascular, kidney, liver or ulcer disease — that is, a deliberately low-risk population. Major adverse cardiovascular events within 30 days of initiation gave an incidence rate ratio of 1.5 (95% CI 1.4 to 1.7) against non-initiators, 1.2 (1.1 to 1.3) against both paracetamol and ibuprofen initiators, and 1.3 (1.1 to 1.5) against naproxen initiators. Every component moved in the same direction: atrial fibrillation or flutter 1.2 (1.1 to 1.4), ischaemic stroke 1.6 (1.3 to 2.0), heart failure 1.7 (1.4 to 2.0), myocardial infarction 1.9 (1.6 to 2.2), cardiac death 1.7 (1.4 to 2.1). The increase was present for low doses of diclofenac as well. Upper gastrointestinal bleeding at 30 days rose approximately 4.5-fold against no initiation and 2.5-fold against ibuprofen or paracetamol. The relative risk was highest in people at low or moderate baseline risk; the absolute risk was highest in those with previous myocardial infarction or heart failure. This is observational, and its design deliberately mimics a randomised trial that, as the European Society of Cardiology has stated, current concerns now make unethical to run.
Written into the record, not signed off as a reviewed claim
Its risk is comparable to the drug that was withdrawn worldwide — and it is the world’s best-selling NSAID
In plain words
Rofecoxib was pulled from every market on earth in 2004 for cardiovascular toxicity. A published comparison of the same evidence base ranks diclofenac alongside it, and the same paper found diclofenac on 74 national essential medicines lists with a market share close to the next three NSAIDs combined.
What was measured
Relative cardiovascular risk ranking by molecule, national essential medicines list entries, and NSAID market share across 15 countries
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The analysis compared relative risks of cardiovascular events for individual NSAIDs, derived from meta-analyses of randomised trials and controlled observational studies, against national essential medicines list entries and against sales or prescription data from 15 low-, middle- and high-income countries. Three drugs ranked consistently highest for cardiovascular risk against non-use: rofecoxib, diclofenac and etoricoxib. Naproxen was associated with a low risk. Diclofenac was listed on 74 national essential medicines lists and naproxen on 27. Diclofenac and etoricoxib together accounted for a third of all NSAID use across the 15 countries (median 33.2%, range 14.7% to 58.7%), and that proportion did not vary between low- and high-income countries; diclofenac alone had a market share close to that of the next three most popular drugs combined, while naproxen averaged under 10%. The authors’ conclusion is unambiguous: diclofenac has a risk very similar to rofecoxib, which was withdrawn from worldwide markets owing to cardiovascular toxicity, and diclofenac should be removed from essential medicines lists. It is not on the WHO Model List. The conclusion shift here is one the market has not yet made.
Written into the record, not signed off as a reviewed claim
It is also, by a clear margin, the most effective NSAID for arthritis pain
In plain words
The case against diclofenac would be easy if it were no better than the alternatives. It is better. In the largest network comparison, diclofenac 150 mg a day produced the biggest pain reduction of any anti-inflammatory at a maximally approved dose.
What was measured
Effect size for osteoarthritis pain against placebo, by preparation and daily dose, with probability of exceeding a minimum clinically important difference of -0.37
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The network meta-analysis pooled 76 randomised trials with 58,451 patients across 23 treatment nodes covering seven NSAIDs and paracetamol at specified daily doses, with a prespecified minimum clinically important effect size for pain of -0.37. Six preparations cleared that threshold with at least 95% probability: diclofenac 150 mg/day, etoricoxib at 30, 60 and 90 mg/day, and rofecoxib at 25 and 50 mg/day. Among maximally approved daily doses, diclofenac 150 mg/day (effect size -0.57, 95% credible interval -0.69 to -0.45) and etoricoxib 60 mg/day (-0.58, -0.74 to -0.43) had the highest probability of being the best intervention, both with 100% probability of reaching the minimum clinically important difference. Treatment effects increased with dose, though the test for a linear dose effect reached significance only for naproxen. The authors state plainly that diclofenac 150 mg/day is the most effective NSAID available — and immediately add that in view of the safety profile of these drugs, physicians need to consider the result together with all known safety information. Both halves of that sentence belong on this page.
Written into the record, not signed off as a reviewed claim
The topical form works, modestly, and is the one that went over the counter
In plain words
Rubbing diclofenac on a knee is not a placebo. In pooled trials about 60% of patients had much reduced pain, giving a number needed to treat of about 10 — a smaller effect than the tablet, at a fraction of the exposure that drives the heart numbers.
What was measured
Number needed to treat for clinical success with topical diclofenac over 6 to 12 weeks in osteoarthritis
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Cochrane review of topical NSAIDs for chronic musculoskeletal pain included 39 studies and 10,631 participants, all in osteoarthritis, with 33 studies comparing a topical NSAID against carrier. In studies lasting 6 to 12 weeks, topical diclofenac and topical ketoprofen were significantly more effective than carrier, with about 60% of participants achieving much reduced pain. For topical diclofenac the number needed to treat for clinical success — at least a 50% reduction in pain or an equivalent global assessment — was 9.8 (95% CI 7.1 to 16) across six trials and 2,343 participants, rated moderate quality evidence. The regulatory consequence is that in the United States the formulation switched to over-the-counter status is the gel, under NDA 022122, not the tablet. That is an unusually rational allocation: the route with the least systemic exposure is the one available without a consultation.
Written into the record, not signed off as a reviewed claim
Diclofenac residues collapsed the vulture populations of South Asia
In plain words
Three species of Gyps vulture declined by more than 95% across the Indian subcontinent from the 1990s. The cause was traced to veterinary diclofenac in livestock carcasses, which caused renal failure in birds that fed on them, and reproduced experimentally.
What was measured
Vulture colony mortality and population decline correlated with tissue diclofenac residues, with experimental reproduction of renal failure
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Oriental white-backed vulture (Gyps bengalensis) was once one of the most common raptors in the Indian subcontinent. A population decline exceeding 95% beginning in the 1990s, also involving Gyps indicus and Gyps tenuirostris, left all three listed as critically endangered. Study sites at 16 colonies in Pakistan measuring mortality at over 2,400 active nest sites recorded annual adult and subadult mortality of 5% to 86% and population declines of 34% to 95% between 2000 and 2003, associated with renal failure and visceral gout. The authors directly correlated diclofenac residues with renal failure, and reproduced both the residues and the renal disease experimentally by direct oral exposure and by feeding vultures diclofenac-treated livestock. Veterinary diclofenac was subsequently banned across several South Asian countries. This is on a human drug page for a reason: it is the clearest demonstration that the renal prostaglandin dependence which makes NSAIDs hazardous to a dehydrated human kidney is not a small-print effect, and it is a rare case where a drug’s toxicity was established by a controlled experiment in the affected population.
Written into the record, not signed off as a reviewed claim
The gel is assumed to be free of the systemic risk. Nothing has measured that.
In plain words
Topical diclofenac is sold over the counter in the United States on the reasoning that very little of it reaches the bloodstream. That reasoning is sound and it has never been tested against a cardiovascular or gastrointestinal outcome — every trial of the gel measured pain over six to twelve weeks.
What was measured
That topical diclofenac carries no meaningful systemic cardiovascular or gastrointestinal risk — a widely accepted premise supported by pharmacokinetics, never tested against a clinical outcome, and not adopted by the product label
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Cochrane review of topical NSAIDs opens by stating the premise directly: use of topical non-steroidal anti-inflammatory drugs to treat chronic musculoskeletal conditions has become widely accepted because they can provide pain relief without associated systemic adverse events. What the review then contains is 39 studies in 10,631 participants, all in osteoarthritis, with pooled analyses over 6 to 12 weeks and some studies judged at risk of bias from short duration and small size. No trial of that design in that population could detect a myocardial infarction signal, and none set out to. The pharmacokinetic argument is real — topical application produces a small fraction of the plasma concentration of an oral dose — but a small fraction of a risk that rises 41% for major vascular events and appears within 30 days of starting the oral drug is a quantity nobody has put a number on. The regulator has not adopted the inference either: the topical products retain the NSAID cardiovascular thrombotic and gastrointestinal warnings on their labels rather than dropping them. This audit is not an argument against topical diclofenac, which has a measured benefit at a number needed to treat of 9.8. It is a statement that "topical, therefore systemically safe" is an inference from a pharmacokinetic property, not a finding.
This order is fixed in code and does not count clicks or time on the page.
What is not here
4 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.
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.
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.
The most effective NSAID for osteoarthritis pain in a network meta-analysis of 58,451 patients (effect size -0.57, 100% probability of clinical relevance) and the one whose cardiovascular risk profile is closest to the withdrawn rofecoxib — major vascular events up 41% in randomised trials, major adverse cardiovascular events up 50% within 30 days of starting it in 1.37 million Danish initiators, including at low doses.
Recorded evidence blocks (13)
Q2
What did Diclofenac's largest trial (7297 people) and its longest (14 years) measure?
7297 people in Diclofenac's largest registered study, 14 years in its longest registered window, measuring physical function. ClinicalTrials.gov · 2026-09-01
76 phase4, 63 phase3, 59 na, 36 phase2, 28 phase1, 8 na or unstated, 5 early phase1; NCT05829707; 2023-04-05. Last human test completed 2026, NCT07565012.
Interpretation These counts include studies where Diclofenac 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
76
phase3
63
na
59
phase2
36
phase1
28
na or unstated
8
2 more recorded rows
early phase1
5
Last recorded human testNCT07565012
2026-03-25
recorded 2026-09-01 · last checked 2026-09-04
Q3
From mouse to human: where has Diclofenac shown healthspan?
futility/efficacy (3), accrual/recruitment (5), funding/business (2), sponsor decision unspecified (1) and other (11): Diclofenac's stop wording, clustered. ClinicalTrials.gov · 2026-09-01
"See Detailed Description"; 22 of 260 registered studies
Show the evidence
Trial
NCT00139646
terminated; "See Detailed Description"
NCT00276419
terminated; "Lack of funds; FDA approved a topical form of diclofenac during study, no need to continue study of pharmacy-compounded drug."
NCT00428025
terminated; "slow recruitment"
NCT00640705
terminated; "Sponsor decision"
NCT00864097
terminated; "See termination reason in detailed description."
NCT00894790
terminated; "See termination reason in detailed description."
14 further recorded trials
NCT00954785
withdrawn; "The study was terminated by Merck USA. The company did not supply drugs for the study."
NCT01019980
terminated; "Placebo - Active Drug Not Available. No patients received drug. There are no study results to disclose."
NCT01039545
terminated; "New power calculation (reduction of necessary patient number)"
NCT01190722
withdrawn; "The study site was closed down"
NCT01413854
withdrawn; "Not enough recources."
NCT01481610
terminated; "Interim analysis shows harma to one of the study arms."
NCT01590342
terminated; "Low recruitment rate"
NCT02094807
withdrawn; "Slow inclusion rate. Awaiting results from NCT02132416."
NCT02556970
withdrawn; "Study never started and was abandoned."
NCT02689024
terminated; "recruitment too slow; intervention was standard care in patients who were not included; acute care pathways changed due to policy regarding hip fracture patients"
NCT03473665
terminated; "Slow recruitment"
NCT03796403
terminated; "Diclofenac is no longer recommend for intramuscular administration by the Medical Council of Thailand"
NCT03949673
terminated; "Lack of enrollment"
NCT04067492
terminated; "In view of the continuing insufficient patient recruitment in the study due to the difficult epidemiological situation and the need for rational allocation of company resources, as well as based on the results of the interim analysis."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Diclofenac used Diclofenac Topical Sodium Gel 1% — over how long?
More Diclofenac was worse in human: at what point?
Hormetic in human: "In this study, a hormesis phenomenon was observed and analysed during toxicity tests of wastewater from constructed wetlands containing two pharmaceutical substances, diclofenac (DCF) and sulfamethoxazole (SMX), against the marine bacteria Aliivibrio fischeri." Europe PMC · dose-response search · 2026-07-27
5 recorded sentences naming Diclofenac; hormesis, biphasic, dose-response
Show the evidence
hormesisPMID 32041071
"In this study, a hormesis phenomenon was observed and analysed during toxicity tests of wastewater from constructed wetlands containing two pharmaceutical substances, diclofenac (DCF) and sulfamethoxazole (SMX), against the marine bacteria Aliivibrio fischeri."
biphasicPMID 42516168
"This biphasic translational study describes the pharmaceutical development and preliminary clinical evaluation of a novel gelatin-carboxymethylcellulose hybrid diclofenac potassium-medicated lollipop, produced in three weight-adjusted paediatric dose strengths (15 mg, 20 mg, and 30 mg)."
dose-responsePMID 41562034
"Four NADs with different mechanisms of action were included at a high (mg/L) and low (μg/L) dose to establish dose-response relationships: chlorpromazine (antipsychotic), diclofenac (anti-inflammatory), diphenhydramine (antihistamine), and fluoxetine (antidepressant)."
biphasic
PMID 38543261
"Sodium diclofenac release was found to be higher when combined with camphor, which revealed the advantages of the biphasic formulation."
PMID 34071381
"Novel calcium phosphate-based starter pellets were used to develop a biphasic-release multiple-unit pellet system (MUPS) with diclofenac sodium as a model drug in the form of hard gelatin capsules."
recorded 2026-07-27 · last checked 2026-09-04
Q7
Which of 1st peak rms knee index, acute pseudophakic cystoid macular edema and area under the concentration time curve did Diclofenac's trials measure?
1st peak rms knee index, acute pseudophakic cystoid macular edema and area under the concentration time curve lead 40 outcome terms across Diclofenac's trials. ClinicalTrials.gov · 2026-09-01
Interpretation post ercp pancreatitis, acute pseudophakic cystoid macular edema, rated visual analogue scale pain intensity assessment, global pain intensity as assessed by visual analog scale, assessment of pain visual analogue scale and s assessment of ankle pain vas follow.
Post-ERCP pancreatitis; Measure of pain during the WHAT test; latest 2028-12-31
Show the evidence
Trial
NCT03595150
"Diclofenac for Prevention of Post-ERC Pancreatitis"; n 1000; "Post-ERCP pancreatitis"; 2028-12-31
NCT06012097
"Impact of Gel Aromatherapy on Pain for Patients With De Quervain Disease"; n 70; "Measure of pain during the WHAT test"; 2026-04-01
NCT06029296
"Diclofenac as a KMO Inhibitor"; n 12; "Kynurenic Acid"; 2026-08
NCT06053411
"Contribution of UGT2B17 to the Pharmacokinetics of Diclofenac"; n 30; "Diclofenac area under the concentration vs. time curve (AUC) in UGT2B17 extensive metabolizers (EMs)"; 2026-12-18
NCT06158620
"Intra-nasal Ketorolac for Acute Ureteral Stent-associated Pain Following Ureteroscopy for Stone Disease"; n 80; "Change in pain scores as measured by USSQ Pain Survey"; 2027-12-01
NCT06207253
"The Antimicrobial Potential of Diclofenac Sodium as an Intracanal Medicament"; n 48; "Bacterial count"; 2025-12
14 further recorded trials
NCT06373978
"NonNarcotic Pain Control in Percutaneous Needle Tenotomy of Elbow"; n 92; "Number of pills taken"; 2027-06-30
NCT06623929
"Topical Treatments for Ankle Sprains"; n 100; "Drugs and Pain"; 2024-11-01
NCT06636227
"Diclofenac Dose Response Study"; n 24; "Change in blood kynurenic acid (KYNA) levels"; 2026-08-31
NCT06731270
"Diclofenac for the Treatment of Patients With Metastatic Non-small Cell Lung Cancer on Single Agent Immunotherapy"; n 20; "Clinical benefit rate (CBR)"; 2028-01-01
NCT06905561
"Topical Diclofenac for Prevention of Radiation-induced Dermatitis"; n 156; "Incidence of development of grade ≥ 2 RID"; 2026-08-31
NCT06918340
"Evaluation of Analgesic Efficacy of Lidocaine and Diclofenac Spray in Radial Artery Blood Gas Sampling by Visual Analogue Scale and Perfusion Index"; n 150; "Change in pain scores associated with radial artery blood gas sampling"; 2025-06-30
NCT06937853
"Effect of Genetic Polymorphisms on Response to Preoperative NSAIDs in Endodontic Postoperative Pain Management"; n 200; "Postoperative pain intensity"; 2025-08-03
NCT06967363
"Multimodal Imaging and Biospecimen Collection for Low Back Pain (LBPB)"; n 360; "Pain Intensity (Brief Pain Inventory - Short Form)"; 2028-12-31
NCT07071441
"Indomethacin vs Diclofenac for Preventing PEP"; n 4050; "Rate of post-ERCP Pancreatitis"; 2026-12-31
NCT07101016
"Effect of Local Use of Non-steroidal Anti-inflammatory Agent (Diclofenac Sodium) With and Without Hyaluronidase on Post-surgical Pain and Swelling"; n 44; "Postoperative pain intensity"; 2025-08-08
NCT07203651
"Comparison Between Diclofenac and Sterile Water Injection for Relief of Labour Associated Bachache"; n 100; "Pain relief"; 2026-07-01
NCT07237620
"The Effect of Different Intracanal Medicaments on Periapical Lesion Healing"; n 60; "Periapical Lesion Healing"; 2027-04-01
NCT07493226
"Efficacy of Chemically Distinct Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Pain Phenotypes in Adhesive Capsulitis"; n 120; "VAS pain (0-10) (night and movement)"; 2027-03-30
NCT07743372
"Effect of Preoperative Diclofenac Potassium Dose on Endodontic Pain"; n 90; "Anesthetic success of articaine buccal infiltration"; 2028-02
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which 120 trials of Diclofenac posted no result?
Posted no result
120 of 120 completed trials
Registrations
NCT00913224, NCT02088411, NCT00649610, NCT00671320, NCT00371696 and NCT00650598, and 114 more
Completion dates
oldest 1993-04; newest 2024-07-26
Show the evidence
Trial
NCT00913224
1993-04
NCT02088411
2001-11
NCT00649610
2003-05
NCT00671320
2003-10
NCT00371696
2003-12
NCT00650598
2004-08
14 further recorded trials
NCT00640432
2004-10
NCT02658799
2004-12
NCT00648141
2005-01
NCT00174317
2005-02
NCT00171626
2005-06
NCT00221052
2005-07
NCT00171678
2005-08
NCT00108992
2005-09
NCT00171652
2005-10
NCT00171665
2005-12
NCT00171691
2006-06
NCT00377806
2006-09
NCT00474136
2007-05
NCT00426621
2007-06
Q10
At the median, Diclofenac's trials enrolled 90.5 people — anything larger?
Median enrolment
90.5
Largest enrolment
7297
Registered trials counted
256
Q11
What do 18452 spontaneous reports say about Diclofenac — 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.
Diclofenac appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 18452 reaction mentions were counted: pain 2298; rheumatoid arthritis 2108; rash 2065; fatigue 2044. open-targets-adr · CHEMBL1034 · 2026-06-24
Show the evidence
pain
2298
rheumatoid arthritis
2108
rash
2065
fatigue
2044
abdominal discomfort
1860
alopecia
1655
4 more recorded rows
pemphigus
1629
systemic lupus erythematosus
1622
glossodynia
1605
swelling
1566
recorded 2026-06-24 · last checked 2026-09-04
Q12
Diclofenac and CYP3A4: shared by which compounds?
CYP3A4 appear in Diclofenac's recorded interaction sentences, 1 in all. openfda-label+europepmc · 2026-08-30
Interpretation pharmacokinetics
Show the evidence
CYP3A4pharmacokinetics
CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy and 3'-hydroxy-diclofenac.
recorded 2026-08-30 · last checked 2026-09-04
Q13
Was Diclofenac studied with fasting and exercise?
fasting and exercise are named in Diclofenac's label sentences: "Subjects received, in randomized order, SoluMatrix diclofenac 18- or 35-mg capsules in the fasting condition, SoluMatrix diclofenac 35-mg capsules under fed conditions, and diclofenac potassium IR 50-mg tablets under fasting and fed conditions." openfda-label+europepmc · 2026-08-30
2 recorded statements; fasting, exercise
Show the evidence
fasting
Subjects received, in randomized order, SoluMatrix diclofenac 18- or 35-mg capsules in the fasting condition, SoluMatrix diclofenac 35-mg capsules under fed conditions, and diclofenac potassium IR 50-mg tablets under fasting and fed conditions.
exercise
After exercise, subjects reporting DOMS received topical diclofenac sodium gel 1% (DSG 1%) applied to one leg and placebo to the other every 6 hours for 48 hours.
recorded 2026-08-30 · last checked 2026-09-04
Q14
What is recorded about Diclofenac and sirtuin?
"This study evaluated the dose-dependent protective effects of the ROCK inhibitor, fasudil, against diclofenac-induced damage and investigated the underlying ROCK2/TLR4/SIRT1 axis." — where Diclofenac and sirtuin appear together. Europe PMC · pathway abstract search · 2026-08-02
"This study evaluated the dose-dependent protective effects of the ROCK inhibitor, fasudil, against diclofenac-induced damage and investigated the underlying ROCK2/TLR4/SIRT1 axis."
autophagy
PMID 38758516
"In the co-culture experiment involving exosomes and intestinal epithelial cell-6 (IEC-6) cells, the results of qRT-PCR, western blotting, and immunofluorescence assays demonstrated that the elevated expression of lncRNA H19 in the small intestine, conveyed via exosomes derived from the diclofenac group, suppressed the expression levels of autophagy-associated protein 5 (Atg 5) and light chain 3…"
PMID 38758516
"These findings significantly elucidated that BBR promoted the restoration of autophagy in IECs by inhibiting exosomal lncRNA H19, thereby mitigating the impairment of the intestinal mucosal mechanical barrier function in diclofenac enteropathy."
PMID 35624874
"We observed that diclofenac inhibits both phagophore movement, an early step of autophagy, and the fusion of autophagosomes and lysosomes, a late step of autophagy."
sirtuinPMID 39579210
"In our research, we evaluated the preventive and therapeutic effects of ART in Diclofenac (DIC) induced kidney injury through its effect on mitochondria and regulation of sirtuin 3 (SIRT3)."
AMPK
PMID 27792760
"To explore whether AMPK activation could potentially prevent or reverse the effects of drug-induced mitochondrial and hepatocellular damage, we added an AMPK activator to collagen sandwich cultures of rat and human hepatocytes exposed to the hepatotoxic drugs, acetaminophen or diclofenac."
PMID 26049010
"Our results showed that the non-selective acidic NSAIDs ibuprofen and diclofenac induced AMPK activation similar to aspirin while the COX-2 selective drug etoricoxib and the non-opioid analgesic paracetamol, both drugs have no acidic structure, failed to activate AMPK."
PMID 26049010
"In conclusion, our results revealed that AMPK can be activated by specific non-steroidal anti-inflammatory drugs such as salicylic acid, ibuprofen or diclofenac possibly depending on the acidic structure of the drugs."
mTORPMID 31246934
"The evaluated treatments were cancer-specific interventions (acitretin, imiquimod, photodynamic therapy, nicotinamide, topical diclofenac, and selenium) and immunosuppression regimes (azathioprine, mycophenolate mofetil, calcineurin inhibitors, mammalian target of rapamycin [mTOR] inhibitors, belatacept, induction agents, and withdrawal of calcineurin inhibitors or corticosteroids)."
NAD+
PMID 16890207
"Inhibition of the malate-aspartate shuttle by diclofenac with a resultant decrease in the ability of mitochondria to generate NAD(P)H was demonstrated."
PMID 16890207
"In conclusion, decreased NAD(P)H production due to an inhibition of the entry of malate and glutamate via the malate-aspartate shuttle explained the more pronounced decreased rate of ATP biosynthesis from glutamate and malate by diclofenac."
recorded 2026-08-02 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 5 required field(s) not terminal: Why people use it, Best-supported result, Most important common problem, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 11 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.