Review A Perspective on the Role of Metformin in Treating [...] (ME/CFS) and Long COVID (2025) Fineberg et al

[Jonathan Edwards]

Sounds like your position might be that without trailed treatments the clinicians should offer no advice or recommendations. The patient goes through the expense of diagnosis process and at the end are told that there is nothing they can try. Is that right?

I find it quite hard to believe that you are questioning this approach @MelbME. It is called being honest with people. Anything else is pretty much a con. You don't so much say there is nothing to try as that you do not know of anything that you have good reason to think will work. You provide support. I had to do that for people with RA for twenty five years before we had medicines that actually worked. It was considered normal and the patients were grateful simply for having someone to advise and answer concerns.

Maybe you are not aware that medical care of ME/CFS is largely quackery - much more so than most other things? These things don't work. We can be pretty sure because if domething really does work it filters through to someone who is motivated to prove it. The reasons why no trials are done is that the clinicians know at heart that they will be negative. I have worked in a field where things didn't work and then things did. ME/CFS is quite clearly in the first category still. Individualised treatment is a myth if nothing works.

 

[OrganicChilli]

There is a massive difference between giving advice on management strategies (pacing) and continuously prescribing unevidenced treatments without ever bother doing a proper trial.

I don’t think we know enough about ME/CFS to justify a blanket ban. If some meds help some patients, they should be available off-label. Everyone has a different risk appetite, and that choice should be the patient’s, not imposed on them.

Some people report improvements of certain symptoms from prescription antihistamines. Afaik, they’ve never been trialled specifically for ME/CFS. In your view, would I not be allowed to request them from my doctor just because I don’t have hay fever? I'm not sensitive to medication and if I don't see an effect, I'll just stop taking them.

 

[Utsikt]

I don’t think we know enough about ME/CFS to justify a blanket ban. If some meds help some patients, they should be available off-label. Everyone has a different risk appetite, and that choice should be the patient’s, not imposed on them.

We have no way of knowing if the meds actually help, that is the whole issue!

And the patient’s risk assessments will almost always be influenced by their doctors, and the doctors don’t seem to be doing a very good job at it. Risk assessments are one of the things I worked with in a non-medical field. You can spot bad ones from a mile away.

Lots of people report improvements from prescription antihistamines. Afaik, they’ve never been trialled specifically for ME/CFS. In your view, would I not be allowed to request them from my doctor just because I don’t have hay fever? I'm not sensitive to medication and if I don't see an effect, I'll just stop taking them.

If you have symptoms that it’s actually reasonable to think might be due to histamines, I don’t see any issue with trying antihistamines in general. But that’s very different from pushing X to everyone for whatever reason.

 

[MelbME]

In an ideal world, everything should be trialled. But pacing is just common sense, it just means to avoid doing things that is usually followed by you feeling a lot worse for a long period of time.

We could probably trial not hitting yourself with a hammer as well, but at some point common sense has to be good enough..

GET isn’t a management strategy, it’s a treatment. I don’t understand what you mean here.

And without any of the BPS trails, I would still say the same: you shouldn’t routinely use treatments before they have been properly tested!

The people that have made their careers as «specialists» have earned more than enough money to do pilots of the treatments they are making money off.

Regardless, the lack of funding isn’t an excuse for using unevidenced treatments for what’s essentially forever.

For what it’s worth, that’s exactly my position wrt treatments. Are you for a different opinion?

Although the HCP could still help with getting aids, getting proper help at home or elsewhere, ensuring the patients get the benefits they have the rights to, helping educate carers and close family, monitoring other health issues, performing regular reassessments of the diagnoses, etc.

Unfortunately pacing isn't common sense. Get outside more, exercise, socialize, improve diet, get psychological therapy. These are usually what default advice looks like.

Specialists in some fields make a lot of money, specialists in fields like ME/CFS don't. They actually make less than staying a standard GP.

I don't see treatment and management as separate things. I'd say treatments are a part of management. So I don't think we define these words the same way.

No one is trying to make an excuse. I'm pointing out the reality of what occurs already in the real world and has been for decades.

 

[Jonathan Edwards]

Get outside more, exercise, socialize, improve diet, get psychological therapy. These are usually what default advice looks like.

And since when was that common sense if you feel awful when you do things? These are just the rhetoric of therapist professionals who want your money repeated by the self-satisfied well.

Specialists in some fields make a lot of money, specialists in fields like ME/CFS don't. They actually make less than staying a standard GP.

Which rather suggests they went into it because they weren't that good at coping with the demands of GP?

Pacing is the default for anyone not persuaded to do exercises, so what do you test it against? Nobody is claiming it produces improvement.

 

[MelbME]

Humors were all the rage for centuries. And BPS folks have also been prescribing their treatment for decades.

Again, how is that any different?

It's not any different. That's my point. People already suggest things without trialling them.

So you're equating any non-trialled advice or recommendation as equal. Giving something with a high risk of harm and few reports of helping patients is equal in your opinion to trying something with low risk of harm and many reports of helping people. Is that right?

 

[Utsikt]

Unfortunately pacing isn't common sense. Get outside more, exercise, socialize, improve diet, get psychological therapy. These are usually what default advice looks like.

There might be a language barrier here from my side. What I intended to say is that if you look at what happens to pwME/CFS when they get PEM, the only remotely reasonable conclusion can be that they should avoid PEM.

I agree that the default advice for sick people is usually something else.

Specialists in some fields make a lot of money, specialists in fields like ME/CFS don't. They actually make less than staying a standard GP.

I don’t know if that holds in every country, but it’s not central to the argument so we can leave it at that.

I don't see treatment and management as separate things. I'd say treatments are a part of management. So I don't think we define these words the same way.

I think you’re confusing two different concepts here.

When someone says that pacing is a «management strategy», they mean that it’s a way for the patient to adapt in their everyday life to the limitations and disability caused by their illness.

When a practitioner talks about how to best «manage a patient», that will include everything from the aforementioned management strategy, to medications, aids, help, benefits, etc.

Regardless, whatever you want to call it, continuously prescribing medications based on virtually no evidence isn’t ethical.

 

[OrganicChilli]

If you have symptoms that it’s actually reasonable to think might be due to histamines, I don’t see any issue with trying antihistamines in general. But that’s very different from pushing X to everyone for whatever reason.

If I take one drug at a time and have a stable baseline or a specific symptom that bothers me, I can usually tell whether it’s making a difference. I’m happy to trial (low-risk) drugs if there’s a chance I could regain some functionality. For someone mild/moderate, the potential benefits outweigh the risks. Most likely, nothing will happen anyway.

I’d hate for a doctor to refuse to consider antihistamines just because I have ME/CFS and can’t explain why it might help. My only reason is an internet anecdote suggesting it helped someone with noise sensitivity (which makes no sense to me btw, but I'm not interested enough in biology to research every detail). Could be coincidence, could be real and I want to find out of it works for me without having to wait for a trial that will never happen.

 

[MelbME]

And since when was that common sense if you feel awful when you do things? These are just the rhetoric of therapist professionals who want your money repeated by the self-satisfied well.


Which rather suggests they went into it because they weren't that good at coping with the demands of GP?

Pacing is the default for anyone not persuaded to do exercises, so what do you test it against? Nobody is claiming it produces improvement.

That's not just the rhetoric of therapist professionals, that's the advice of standard GPs who don't know enough about the condition.

No they go in to specializing ME/CFS because they usually know someone with the condition and want to help the many without help. It's far easier to be a standard GP.

Pacing is not the default recommendation for ME/CFS by GPs, it's the default of GPs that are ME/CFs literate (which is rarer).

 

[MelbME]

There might be a language barrier here from my side. What I intended to say is that if you look at what happens to pwME/CFS when they get PEM, the only remotely reasonable conclusion can be that they should avoid PEM.

I agree that the default advice for sick people is usually something else.

I don’t know if that holds in every country, but it’s not central to the argument so we can leave it at that.

I think you’re confusing two different concepts here.

When someone says that pacing is a «management strategy», they mean that it’s a way for the patient to adapt in their everyday life to the limitations and disability caused by their illness.

When a practitioner talks about how to best «manage a patient», that will include everything from the aforementioned management strategy, to medications, aids, help, benefits, etc.

Regardless, whatever you want to call it, continuously prescribing medications based on virtually no evidence isn’t ethical.

Pacing isn't simply rest, that might be common sense. It usually requires some intervening information on how to do it. Most patients without advice on how to really do pacing will simply rest and then when feeling better they will be active again. Just listening to their body gets them in to trouble. Pacing is different. At least how I define it.

Maybe after resting and being active and getting PEM in ongoing cycles eventually teaches the patient, point of pacing as an intervention is to get the patient to the point of understanding to rest when they feel well and looking for warning signs far earlier than they would land naturally by self-learning.

 

[Utsikt]

It's not any different. That's my point. People already suggest things without trialling them.

How does that justify continuing doing it? You’re essentially saying that just because it’s the standard thing to do, we should keep doing it. That obviously don’t hold up under scrutiny.

So you're equating any non-trialled advice or recommendation as equal.

We’ve already been through the «common sense» thing, so no.

Giving something with a high risk of harm and few reports of helping patients is equal in your opinion to trying something with low risk of harm and many reports of helping people. Is that right?

That’s not at all what I’ve been saying. The question isn’t if they are equal, but if any of them reach the threshold of being 1) reasonably expected to help based on a sound rationale, 2) sufficiently safe, 3) at a reasonable cost compared to the expected benefit.

All medications carry some risk, so they all start at net negative. All medications have a financial cost, so they all start at a net negative. Then it’s up to the practitioner to argue for why 1 (expected benefit) outweighs 2 (risk) and 3 (cost).

That’s not accounting for the time that might be wasted, the harm done by false hope, the harm done by pressure from everyone around you to try literally anything, the stress and discomfort from trialing treatments and constantly taking risks, etc.

I get the feeling that you don’t really understand the potential downsides from the patient’s point of view.

 

[Utsikt]

If I take one drug at a time and have a stable baseline or a specific symptom that bothers me, I can usually tell whether it’s making a difference.

There’s a reason we need placebo controlled trials..

I’m happy to trial (low-risk) drugs if there’s a chance I could regain some functionality. For someone mild/moderate, the potential benefits outweigh the risks. Most likely, nothing will happen anyway.

Due to the world we live in, that’s up to you to decide because you’ll find someone that’s willing to let you try it if you want.

 

[MelbME]

I find it quite hard to believe that you are questioning this approach @MelbME. It is called being honest with people. Anything else is pretty much a con. You don't so much say there is nothing to try as that you do not know of anything that you have good reason to think will work. You provide support. I had to do that for people with RA for twenty five years before we had medicines that actually worked. It was considered normal and the patients were grateful simply for having someone to advise and answer concerns.

Maybe you are not aware that medical care of ME/CFS is largely quackery - much more so than most other things? These things don't work. We can be pretty sure because if domething really does work it filters through to someone who is motivated to prove it. The reasons why no trials are done is that the clinicians know at heart that they will be negative. I have worked in a field where things didn't work and then things did. ME/CFS is quite clearly in the first category still. Individualised treatment is a myth if nothing works.

What do you mean provide support and advise? What does that look like?

No management with medications that haven't been trialled in that disease? No pain meds? Nothing that hasn't gone through clinical trials for that disease?

I am aware that it's largely quackery, I think what you're saying is that it's all quackery. I'm thinking amongst the quackery there is better forms of advice than others. I don't think it's black and white.

 

[Utsikt]

Pacing isn't simply rest, that might be common sense. It usually requires some intervening information on how to do it. Most patients without advice on how to really do pacing will simply rest and then when feeling better they will be active again. Just listening to their body gets them in to trouble. Pacing is different. At least how I define it.

Maybe after resting and being active and getting PEM in ongoing cycles eventually teaches the patient, point of pacing as an intervention is to get the patient to the point of understanding to rest when they feel well and looking for warning signs far earlier than they would land naturally by self-learning.

Pacing = avoiding PEM while maximising functional capacity and/or quality of life.

That can include looking for consistent warning signs and resting until you feel well, but PEM can happen without any warning signs.

And it doesn’t matter if it’s intuitive or not. We’re talking about what’s very obviously logical based on the observed patterns of symptoms worsening following exertion, i.e. PEM.

 

[MelbME]

Pacing = avoiding PEM while maximising functional capacity and/or quality of life.

That can include looking for consistent warning signs and resting until you feel well, but PEM can happen without any warning signs.

And it doesn’t matter if it’s intuitive or not. We’re talking about what’s very obviously logical based on the observed patterns of symptoms worsening following exertion, i.e. PEM.

But the pattern of symptoms don't always worsen after all exertion. If it was easy and logical then PEM would rarely occur. Which might be true for some but not all.

 

[Trish]

But clinicians have been prescribing it, for decades. Treatments get trialled on patients already if they have minor side effects. Only the treatments that are seen as risky or very expensive have rapidly gone in to treatment trials for ME.

Sounds like your position might be that without trailed treatments the clinicians should offer no advice or recommendations. The patient goes through the expense of diagnosis process and at the end are told that there is nothing they can try. Is that right?

No, I don't think that. I think clinicians should provide general advice about pacing if the pwME is inexperienced and unaware of the possiblity of long term deterioration from keeping on pushing themselves into PEM. And they should offer symptomatic treatment if the pwME asks for it for pain, nausea and sleep problems, and things like referral to dieticians if there are feeding problems, referral to OT for equipment and adaptations, reports for employers and benefits agencies, regular checkups for other conditions - all the stuff any good doctor should provide as needed.

Just because there isn't a cure for ME/CFS yet, doesn't mean there is no supportive care and symptomatic treatment a doctor can and should provide. I had a friend with motor neuron disease, for which there was no curative treatment and from which she died. She had good medical care and support at all stages of her disease even though there was no treatment for the disease itself.

 

[Utsikt]

But the pattern of symptoms don't always worsen after all exertion.

Have I said it does?

If it was easy and logical then PEM would rarely occur. Which might be true for some but not all.

In general, there are three main causes of PEM when pacing:

1. Being forced to do more than you know you can due to circumstances outside your control.
2. Natural fluctuations that makes an average day sometimes result in PEM because you’re trying to maximise FC/QoL
3. Doing more than you know you probably should because you want to do something

It’s obviously not just about «doing», external stimuli etc. also plays a role.

Besides, logical does not mean that it has to be easy to implement. I’ve never claimed pacing is easy, and most would probably say it’s very difficult.

That doesn’t make it any less logical.

 

[MelbME]

How does that justify continuing doing it? You’re essentially saying that just because it’s the standard thing to do, we should keep doing it. That obviously don’t hold up under scrutiny.

We’ve already been through the «common sense» thing, so no.

That’s not at all what I’ve been saying. The question isn’t if they are equal, but if any of them reach the threshold of being 1) reasonably expected to help based on a sound rationale, 2) sufficiently safe, 3) at a reasonable cost compared to the expected benefit.

All medications carry some risk, so they all start at net negative. All medications have a financial cost, so they all start at a net negative. Then it’s up to the practitioner to argue for why 1 (expected benefit) outweighs 2 (risk) and 3 (cost).

That’s not accounting for the time that might be wasted, the harm done by false hope, the harm done by pressure from everyone around you to try literally anything, the stress and discomfort from trialing treatments and constantly taking risks, etc.

I get the feeling that you don’t really understand the potential downsides from the patient’s point of view.

I just said "no one is making an excuse for it" and then you ask "how does that justify it?". I don't know if you're reading all of what I'm saying. I get the feeling that you're misunderstanding me and skipping past things I'm writing that would help you understand me.
And I feel like I'm misunderstanding you too.

 

[MelbME]

Have I said it does?

In general, there are three main causes of PEM when pacing:

1. Being forced to do more than you know you can due to circumstances outside your control.
2. Natural fluctuations that makes an average day sometimes result in PEM because you’re trying to maximise FC/QoL
3. Doing more than you know you probably should because you want to do something

It’s obviously not just about «doing», external stimuli etc. also plays a role.

Besides, logical does not mean that it has to be easy to implement. I’ve never claimed pacing is easy, and most would probably say it’s very difficult.

That doesn’t make it any less logical.

I felt you implied it in your statement about how very obvious and logical it is to not over exert but it's not all that logical if over exerting isn't obvious or consistent.

But ok, I understand what you mean here.

 

[Utsikt]

I just said "no one is making an excuse for it" and then you ask "how does that justify it?". I don't know if you're reading all of what I'm saying. I get the feeling that you're misunderstanding me and skipping past things I'm writing that would help you understand me.
And I feel like I'm misunderstanding you too.

I’m sorry for missing that. But I don’t understand what «the reality of what people are doing» has to do with if it should be that way, which is what I’ve assumed we’re talking about?

Is there anything else you feel I’ve missed out on?

It’s getting late so I’ll come back to this sometime tomorrow.