Companies fund large trials when a win can be protected and sold. For generics and unpatentable compounds the expected return is low or absent, and most repurposing research is left to academics (Verbaanderd 2020). That explains why metformin for ageing, DMSO and low-dose naltrexone lack decisive trials. It does not mean they work. Public trials of cheap drugs have found big wins, such as dexamethasone in Covid-19, and clear failures, such as LDN in Crohn's disease.
Summary drafted from this entry’s sources; editorial review pending.
01Key questions
Why don't drug companies test cheap generic drugs for new uses?
A 2020 policy review found that approving a new indication is costly while the return for industry is expected to be low or absent once a medicine is out of patent and regulatory protection. Most repurposing research is done by academics.1
Does a missing trial mean the compound works but is being suppressed?
No. It means the question is unanswered. When public funders have run trials of cheap drugs, some worked and some did not; a Dutch placebo-controlled trial of low-dose naltrexone in Crohn's disease was stopped early for futility.9
Can cheap drugs ever get large trials?
Yes, usually with public money. The RECOVERY trial, funded by the UK Medical Research Council and NIHR, showed dexamethasone cut 28-day deaths in hospitalised Covid-19 patients. Colchicine trials funded mainly by public and charitable money, with generic-maker support in one, established low-dose colchicine in heart disease.567
What happened to the TAME metformin trial?
It was proposed in 2016 as the first trial to target ageing itself with metformin. As of late 2026 no results have been published.4
Large randomised trials are expensive and slow. Companies pay for that when a win can be sold under patent or regulatory exclusivity. A cheap generic, a solvent or a molecule anyone can make offers no such return, so the decisive trial often never happens. That is a real gap, and this page documents it. It is also not evidence that the compound works: when public funders do run the trials, cheap compounds sometimes win big and sometimes fail.
02Why the trials are missing
- The return is low or absent. A 2020 policy review of repurposing cancer drugs found that getting a new indication approved carries a high administrative burden and significant costs, while the return on investment for industry is expected to be low or absent for medicines out of patent and regulatory protection. Most repurposing research is done by independent or academic researchers who lack the resources to take a drug through regulators (Verbaanderd 2020, PMID 32076405).
- The science is not the bottleneck. A 2019 review in Nature Reviews Drug Discovery describes old drugs as de-risked compounds with potentially lower development costs and shorter timelines, but lists major technological and regulatory challenges for repurposing (Pushpakom 2019, PMID 30310233).
- Some compounds cannot be owned at all. A 2021 review called DMSO "nonpatentable" and "underexplored and ignored by pharmaceutical developers" (Hoang 2021, PMID 34314611). The authors are advocates of the compound, so read the claim as a description of the incentive, not proof of efficacy.
03Cases on this site
- Metformin for ageing. The TAME trial was proposed in 2016 to test metformin against a composite of age-related diseases (Barzilai 2016, PMID 27304507). Ten years later no results have been published. See metformin and rapamycin.
- Pyridoxamine. A form of vitamin B6 that a drug developer had pulled from US supplement shelves. The drug programme then stopped for lack of money, not because a trial failed. See the drug-exclusion rule.
- DMSO, low-dose naltrexone and low-dose lithium. All are cheap and off-patent, with small trials and large claims. See DMSO, low-dose naltrexone and low-dose lithium.
04When public money runs the trial
The gap is not fixed. Public and charity funders can run trials of cheap drugs, and the results go both ways.
- Dexamethasone. The UK RECOVERY trial, funded by the Medical Research Council and the National Institute for Health Research, randomised 6,425 hospitalised Covid-19 patients. A decades-old generic steroid cut 28-day deaths (22.9% versus 25.7%; rate ratio 0.83) (Horby 2021, PMID 32678530).
- Colchicine. COLCOT, funded by the Government of Quebec and others, found fewer cardiovascular events after a heart attack (5.5% versus 7.1%) (Tardif 2019, PMID 31733140). LoDoCo2, supported by Australian and Dutch public and charitable funders plus a consortium of Dutch generic makers (Teva, Disphar and Tiofarma), found fewer events in chronic coronary disease (6.8% versus 9.6%) (Nidorf 2020, PMID 32865380). Once that evidence existed, a branded low-dose colchicine tablet won FDA approval in 2023, which shows the other route: a company can still make money on an old molecule after someone else has paid for the proof. Then CLEAR SYNERGY, the largest trial after a heart attack, found no benefit (PMID 39555823). See low-dose colchicine.
- Low-dose naltrexone. A Dutch multicentre placebo-controlled trial in active Crohn's disease was stopped early for futility: endoscopic remission was 5.6% with LDN versus 18.8% with placebo, with less fatigue as the only signal (van de Pol 2026, PMID 42701992). A missing sponsor explains why LDN trials are small; it does not explain away a null one.
05How to read a cheap compound's evidence
- "No big trial" means unknown, not proven and not disproven.
- Check the registries for publicly funded trials before assuming nobody has tested it.
- Treat advocates' reviews the way you would treat a sponsor's review: the incentive is reputation or a clinic, not a patent. See industry funding and trial results.
- When a well-run public trial is null, weigh it fully. Cheapness does not make a compound more likely to work.
This page explains how evidence gets made; it is not medical advice.
06Who paid, and how it got here
Who funded the key studies on this page, the favourable and the unfavourable alike, and how its legal status came about. From each paper’s funding and conflict-of-interest statements, trial registries and official documents; checked 1 Nov 2026. Why we show this
Who paid for the key studies
- RECOVERY trial, dexamethasone in Covid-19, n=6,425A cheap generic steroid cut 28-day deaths.Funding and interests: UK Medical Research Council and NIHR (public funding). Paper's funding statement
- COLCOT, colchicine after heart attack, n=4,745Fewer cardiovascular events with colchicine.Funding and interests: Government of Quebec and others (public funding). Paper's funding statement
- LoDoCo2, colchicine in chronic coronary disease, n=5,522Fewer cardiovascular events with colchicine.Funding and interests: Australian and Dutch public/charitable support, plus Teva, Disphar and Tiofarma. Paper's funding statement
07Connections
08Sources
- Verbaanderd C, Rooman I, Meheus L, Huys I. On-label or off-label? Overcoming regulatory and financial barriers to bring repurposed medicines to cancer patients. Front Pharmacol. 2020;10:1664. PMID 32076405PubMed 32076405
- Pushpakom S, Iorio F, Eyers PA et al. Drug repurposing: progress, challenges and recommendations. Nat Rev Drug Discov. 2019;18(1):41-58. PMID 30310233PubMed 30310233
- Hoang C, Nguyen AK, Nguyen TQ et al. Application of dimethyl sulfoxide as a therapeutic agent and drug vehicle for eye diseases. J Ocul Pharmacol Ther. 2021;37(8):441-451. PMID 34314611PubMed 34314611
- Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a tool to target aging. Cell Metab. 2016;23(6):1060-1065. PMID 27304507PubMed 27304507
- RECOVERY Collaborative Group; Horby P et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704. PMID 32678530PubMed 32678530
- Tardif JC et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019. PMID 31733140PubMed 31733140
- Nidorf SM et al. Colchicine in patients with chronic coronary disease. N Engl J Med. 2020. PMID 32865380PubMed 32865380
- Jolly SS et al. Colchicine in acute myocardial infarction. N Engl J Med. 2025. PMID 39555823PubMed 39555823
- van de Pol N, Paulides E, Wolfhagen FHJ et al. Low-dose naltrexone in Crohn's disease: a prematurely terminated randomized trial. Dig Dis Sci. 2026. PMID 42701992PubMed 42701992
09Entry history
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Heretic informs and never prescribes. Where amounts appear, they describe what published studies used. Talk to a qualified clinician before acting on anything here.