SubEx

Pain reliever

Diclofenac

The most effective oral anti-inflammatory for arthritis pain, and the one with the highest heart signal. The gel reaches a similar effect without it.

Findings
6
Best evidence
★★★
Open questions
0

At a glance

Myth check

Diclofenac is just a stronger ibuprofen. Same kind of drug, a bit more punch.

It is more effective for osteoarthritis pain: 150 mg per day was one of only five oral preparations out of 90 tested that cleared the minimal clinically important pain reduction (da Costa et al., 2021). It also carries the highest cardiovascular signal of the widely used non-selective drugs. Pooled randomised data put major vascular events up about a third on high-dose diclofenac (rate ratio 1.41), comparable to the coxibs (Coxib and traditional NSAID Trialists' Collaboration, 2013), and community observational data put it at 1.40 against 1.18 for ibuprofen and 1.09 for naproxen, elevated even at the doses sold without a prescription (McGettigan and Henry, 2011). The topical form is the interesting part: it reaches a similar pain effect for knee osteoarthritis with far lower systemic exposure, and in the same network meta-analysis no topical preparation showed an increased risk of any adverse event.

Diclofenac is not ibuprofen with the volume turned up; it sits at a different point on the trade between pain relief and cardiovascular risk, and switching to the topical form moves that point substantially.

The findingsStrongest first
1↑
Physical & bodyThe heart risk is still there at the dose you can buy yourself

Two independent syntheses landed on 1.40 and 1.41 for major cardiovascular events. The community review found the excess still present at over-the-counter doses, at 1.22.

★★★Well replicated — this finding’s sources average out to meta-analyses, systematic reviews or high-powered trials.The community data are observational, so doctors steering higher-risk patients towards particular drugs cannot be ruled out. A relative risk says nothing about a given reader's own starting point. In the randomised trials the absolute excess came to about three extra major vascular events per 1,000 people treated for a year, one of them fatal. Those trial doses were high and sustained.Click to keep this openSupport heart and blood flow
2∿
PainFive pills out of everything tested clear what patients can notice

Across 192 trials in knee and hip osteoarthritis, five oral preparations had at least a 99% chance of beating the smallest pain drop patients notice. No opioid got past 53%.

★★★Well replicated — this finding’s sources average out to meta-analyses, systematic reviews or high-powered trials.Diclofenac at 150 mg a day, the most effective oral option in the network, also carried a raised risk of people dropping out because of side effects, so the ranking rewards a preparation more people stopped taking. Only English-language trials with at least 100 patients per group were eligible, which leaves the smaller ones out. This covers knee and hip osteoarthritis, not pain in general. Several authors declare consulting relationships with industry.Click to keep this openRelieve pain
3↓
PainFor half or more of people, one tablet never halves the pain

In pooled trials after surgery, 2.5 people had to take 400 mg of ibuprofen for one more to get half their pain gone over four to six hours. Diclofenac and naproxen sat at 2.7.

★★★Well replicated — this finding’s sources average out to meta-analyses, systematic reviews or high-powered trials.Most of the underlying data come from wisdom-tooth extraction in otherwise healthy adults, a standardised research model rather than everyday pain. These are single doses measured over four to six hours and say nothing about taking something repeatedly. The overview ran no statistical test between the drugs, so these numbers sit side by side and were never compared. Some drug and dose combinations were judged unreliable because of susceptibility to publication bias.Click to keep this openRelieve pain
4↓
PainOne diclofenac gel needed 1.8 people treated; other gels needed over 4

Against a dummy gel, diclofenac in one emulsion needed 1.8 people treated for one more to halve their sprain pain, and ketoprofen gel 2.5. The same actives elsewhere needed over 4.

★★★Well replicated — this finding’s sources average out to meta-analyses, systematic reviews or high-powered trials.The best diclofenac figure rests on two studies, and some of the ketoprofen data come from 1980s trials with loosely defined outcomes. Around 5,900 participants' worth of registered but never fully reported efficacy data was identified and could not be obtained, which is the direction publication bias usually runs. Only 220 people across all 61 trials were given a tablet for comparison, so the comparison with swallowing one is thin.Click to keep this openRelieve pain
5↓
PainThe gel came close to the best pills, and raised no side-effect risk

In a network of 192 trials, topical diclofenac at 70 to 81 mg a day had at least a 92% chance of clearing the smallest pain drop patients notice, with no raised adverse-event risk.

★★★Well replicated — this finding’s sources average out to meta-analyses, systematic reviews or high-powered trials.About half the people using the carrier gel alone also counted as a success, roughly twice the usual response to a dummy pill, so part of what people feel comes from the vehicle and the act of rubbing rather than from the drug. Every trial in the topical review was in osteoarthritis, almost all of it knee osteoarthritis. Up to 6,000 participants' worth of completed but unpublished data was unavailable to the reviewers. Trials with fewer than 100 patients per group were excluded from the network.Click to keep this openRelieve pain
6↑
Physical & bodyIbuprofen sat at 1.84 and piroxicam at 7.43 for serious gut trouble

Against taking nothing, the relative risk of a serious upper-gut complication ran 1.84 on ibuprofen, 3.34 on diclofenac, 4.10 on naproxen and 7.43 on piroxicam.

★★☆Single study — solid evidence, such as one good trial or a large observational dataset, but not replicated at the top tier.These come from observational studies whose definitions of a serious complication and methods of recording who took what varied, which the authors flag themselves. The intervals are wide for the less-studied drugs, running from 1.07 to 17.81 for diflunisal. No absolute risk is supplied, and it turns heavily on age and ulcer history. Several of the drugs ranked are not in common use in most markets.Click to keep this openRelieve pain
Sources7 behind this page