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

[Peter T]

Yeah they do. POTS is a more common one. Absolutely, the goal is to try identify treatments of ME/CFS which would be a lot simpler if we knew what the mechanism was.

Doesn't mean clinicians can't help now by trying to manage symptoms while identifying and treating comorbidities. At least some direction away from GET or whatever else gets advised. I think there is a spectrum of advice from good to bad, not simply black or white because people try always look to try something.

This gets dangerously near the BPS arguments that if we have examples of something sometimes helping, eg some people improving at the same times as exercising, then we should be doing exercise and that it is not acceptable to leave people without any treatment (even if we do not have good evidence for any treatment).

 

[Jonathan Edwards]

Yeah they do. POTS is a more common one.

I disagree. This is just the sort of confusion the 'ME experts' peddle. POTS is a hypothetical 'syndrome' supposed to be mediated by events in which tachycardia is crucial. There are two problems with this. Firstly, it is very unclear what role the tachycardia plays if any in these people's symptoms. Secondly the 'syndrome' that is supposed to go along with POT (without the S) is pretty much ME/CFS. So ME/CFS is associated with ME/CFS? ME/CFS includes orthostatic intolerance as a common feature, but as ME/CFS Science Blog has pointed out, the role of POT is very unclear.

I think we need to do better than this sort of muddle.

 

[Trish]

The question of what to refer to as a comorbidity and what is part of ME/CFS is confused, I think, because not everybody with ME/CFS experiences orthostatic intolerance, not all experience pain, not all experience gut problems. But many of us have these symptoms as part of our ME/CFS.

So do we say POTS, fibromyalgia, IBS, headaches, are comorbidities? If they arrived as part of the package of symptoms when ME/CFS with PEM started, and fluctuate as part of the person's ME/CFS, then I think they are symptoms of that person's ME/CFS, not comorbidities, and treatment of them, if available, is part of symptomatic treatment of ME/CFS.

I take co-morbidities to mean if someone, for example, also has asthma, or diabetes that also needs treatment. So 'co-morbidities' is a shorthand way of saying this person has multiple chronic conditions with different onset, causes and treatment.

Having written all that, I looked up the definition:

plural noun: co-morbidities
the simultaneous presence of two or more diseases or medical conditions in a patient.

 

[Jonathan Edwards]

the simultaneous presence of two or more diseases or medical conditions in a patient.

Yes, strictly speaking co-morbidity is just the coincidence of two diseases. In that sense it is irrelevant to the management of ME/CFS itself unless there are potential implications of treating one on the other.

People in the ME/CFS advocacy world have come to use the term co-morbidity to mean other conditions with an increased chance of co-occurrence with ME/CFS and, as we have both noted, there seems little evidence for there being any, over and above features that are recognised as part of ME/CFS anyway.

 

[MelbME]

This gets dangerously near the BPS arguments that if we have examples of something sometimes helping, eg some people improving at the same times as exercising, then we should be doing exercise and that it is not acceptable to leave people without any treatment (even if we do not have good evidence for any treatment).

I'm not sure I understand what you mean here.

What is close to that argument?

 

[MelbME]

I disagree. This is just the sort of confusion the 'ME experts' peddle. POTS is a hypothetical 'syndrome' supposed to be mediated by events in which tachycardia is crucial. There are two problems with this. Firstly, it is very unclear what role the tachycardia plays if any in these people's symptoms. Secondly the 'syndrome' that is supposed to go along with POT (without the S) is pretty much ME/CFS. So ME/CFS is associated with ME/CFS? ME/CFS includes orthostatic intolerance as a common feature, but as ME/CFS Science Blog has pointed out, the role of POT is very unclear.

I think we need to do better than this sort of muddle.

Then why does treatments to improve the postural tachycardia improve the POTS itself to a point of being managed?

 

[Utsikt]

Then why does treatments to improve the postural tachycardia improve the POTS itself to a point of being managed?

There is no evidence of sufficient quality that e.g. betablockers, compression garments or increased salt intake improves the OI part of POTS.

Or have I missed some studies?

 

[Jonathan Edwards]

Then why does treatments to improve the postural tachycardia improve the POTS itself to a point of being managed?

Is there any reliable evidence to that effect? Slowing down tachycardia will presumably remove the symptom of a racing heart (and maybe associated anxiety) but what evidence do we have for that impacting on some other 'syndrome'? I didn't think there were any decent trials for 'POTS' much.

 

[MelbME]

Is there any reliable evidence to that effect? Slowing down tachycardia will presumably remove the symptom of a racing heart (and maybe associated anxiety) but what evidence do we have for that impacting on some other 'syndrome'? I didn't think there were any decent trials for 'POTS' much.

The research field is even smaller than ME/CFS but yes specialists say that most people gave milder cases where treating POTS with salt/water/compression is enough for most to resume life quickly. Often the severe POTS patient are those that have comorbid ME/CFS or long COVID. Those are also the ones more likely to be invested on the disease itself.

Salt/water/compression is considered baseline therapy. Beyond that there haven't been completed drug trials (some are ongoing) but all the specialist clinicians use a similar combination of therapies in different orders.

Prof Satish Raj does a good talk on the topic:

 

[Peter T]

I'm not sure I understand what you mean here.

What is close to that argument?

Sorry I probably shouLd not be posting today, I am struggling with my cognitive posting.

Once I had posted I realised that quoting your post didn’t make sense but I was struggling with how to clarify what I meant. Discussions on more that one thread have been veering towards the suggestion that there are some medications that work for some people and not for others, even though we do not have good trial data to support this. Further at times some seem to be suggesting that because we have not evidenced treatments it is some how more justifiable to try medications that some think might work.

 

[Jonathan Edwards]

The research field is even smaller than ME/CFS but yes specialists say that most people gave milder cases where treating POTS with salt/water/compression is enough for most to resume life quickly. Often the severe POTS patient are those that have comorbid ME/CFS or long COVID. Those are also the ones more likely to be invested on the disease itself.

What 'specialists' say is largely salestalk as far as I can see in this area. The body's homeostatic system keeps volume and sodium levels constant for all of us despite wide variations in input. The likelihood that altering salt and water intake can shift things for people with tachycardia for more than an hour or two seems to me slim and I have not seen any decent studies to the contrary. Without careful trials I don't see that we can assume anything much about the physiology.

Raj gives us a pretty rag-bag mixture of data on all sorts of things including a 3 months exercise programme!!

 

[MelbME]

Sorry I probably shouLd not be posting today, I am struggling with my cognitive posting.

Once I had posted I realised that quoting your post didn’t make sense but I was struggling with how to clarify what I meant. Discussions on more that one thread have been veering towards the suggestion that there are some medications that work for some people and not for others, even though we do not have good trial data to support this. Further at times some seem to be suggesting that because we have not evidenced treatments it is some how more justifiable to try medications that some think might work

No problem at all Peter.

We don't have good trial data and yet some medications already get recommended like LDN or advice is given like pacing or avoid PEM. Clinicians try many things on patients over the years but these stand out as getting ongoing positive feedback in ME/CFS and have even become mainstays in Long COVID treatment.

In the absence of a treatment approved for ME/CFS there is still advice directed to patients by their GP and other people. Often the default has been to exercise more, try vitamins, try drug X, etc. Not saying this advice is justified, just saying that it is given regardless.

The question of what to refer to as a comorbidity and what is part of ME/CFS is confused, I think, because not everybody with ME/CFS experiences orthostatic intolerance, not all experience pain, not all experience gut problems. But many of us have these symptoms as part of our ME/CFS.

So do we say POTS, fibromyalgia, IBS, headaches, are comorbidities? If they arrived as part of the package of symptoms when ME/CFS with PEM started, and fluctuate as part of the person's ME/CFS, then I think they are symptoms of that person's ME/CFS, not comorbidities, and treatment of them, if available, is part of symptomatic treatment of ME/CFS.

I take co-morbidities to mean if someone, for example, also has asthma, or diabetes that also needs treatment. So 'co-morbidities' is a shorthand way of saying this person has multiple chronic conditions with different onset, causes and treatment.

Having written all that, I looked up the definition:

plural noun: co-morbidities
the simultaneous presence of two or more diseases or medical conditions in a patient.

Agreed not everyone has the same set of comorbidities. The plan to treat them is individual and each combination creates some complexity on how to manage them.

The defining of the comorbidities is dependent on the clinician you see, what they pick out first and what they miss. You might get diagnosed as ME/CFS but how long did you have it before diagnosis? Did you have since trigger or did it only become ME/CFS after a few weeks or 6 months?

The questions you ask are interesting and complicated to answer. If anything the answer may be that diagnosis may be leading us astray. But based on current way medicine works, the diagnosis of conditions seems to be the label needed to try a package of treatments that clinicians have had positive feedback on. Even in the absence of trial data.

OMF is currently trialling LDN and mestinon, what are your thoughts on that?

 

[Utsikt]

We don't have good trial data and yet some medications already get recommended like LDN or advice is given like pacing or avoid PEM. Clinicians try many things on patients over the years but these stand out as getting ongoing positive feedback in ME/CFS and have even become mainstays in Long COVID treatment.

In the absence of a treatment approved for ME/CFS there is still advice directed to patients by their GP and other people. Often the default has been to exercise more, try vitamins, try drug X, etc. Not saying this advice is justified, just saying that it is given regardless.

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

The BPS folks also manage to get some patients to report improvement and that they are happy with the treatments. I don’t see how that is any different from this.

OMF is currently trialling LDN and mestinon, what are your thoughts on that?

Someone should have done that ages ago if they believed it was viable. It’s better late than never, though, if the study design is robust?

 

[Trish]

OMF is currently trialling LDN and mestinon, what are your thoughts on that?

My thoughts on that are very straightforward. If they are doing excellently run double blind controlled clinical trials for a decently long time and sample sizes, with clearly diagnosed patients, and with relevant outcome meaures, and report it accurately, I'm all for it. Three cheers for them.

Until they report the results, and the results show clear and lasting benefit, doctors shouldn't be prescibing them in most cases If they do, they should give the patient clear caveats that there is as yet no clinical trial evidence that they work. They shouldn't be telling the patients, how about trying this, some of my patients find it helpful.

 

[MelbME]

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

The BPS folks also manage to get some patients to report improvement and that they are happy with the treatments. I don’t see how that is any different from this.

Someone should have done that ages ago if they believed it was viable. It’s better late than never, though, if the study design is robust?

So you don't think management strategies like pacing should be trialled? I mean without the PACE trial we'd probably have many more patients on GET. What if pacing is doing more harm than good longterm? We don't know and yet some advice you feel comfortable providing, why do you think that is?

Yes trialling is good but it's expensive and it hasn't been common for ME research to attract that type of funding.

 

[MelbME]

My thoughts on that are very straightforward. If they are doing excellently run double blind controlled clinical trials for a decently long time and sample sizes, with clearly diagnosed patients, and with relevant outcome meaures, and report it accurately, I'm all for it. Three cheers for them.

Until they report the results, and the results show clear and lasting benefit, doctors shouldn't be prescibing them in most cases If they do, they should give the patient clear caveats that there is as yet no clinical trial evidence that they work. They shouldn't be telling the patients, how about trying this, some of my patients find it helpful.

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?

 

[Holinger]

My thoughts on that are very straightforward. If they are doing excellently run double blind controlled clinical trials for a decently long time and sample sizes, with clearly diagnosed patients, and with relevant outcome meaures, and report it accurately, I'm all for it. Three cheers for them.

Until they report the results, and the results show clear and lasting benefit, doctors shouldn't be prescibing them in most cases If they do, they should give the patient clear caveats that there is as yet no clinical trial evidence that they work. They shouldn't be telling the patients, how about trying this, some of my patients find it helpful.

Funnily enough I was told exactly this a month ago. The doctor brought LDN up, said it was a bit of a desperate move but they have a rheumatologist that can trial it with me if I wish because it is pretty safe. It and others should definitely be on the table if the safety profile is ok.

 

[Utsikt]

So you don't think management strategies like pacing should be trialled?

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..

I mean without the PACE trial we'd probably have many more patients on GET.

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!

Yes trialling is good but it's expensive and it hasn't been common for ME research to attract that type of funding.

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.

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?

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.

 

[Utsikt]

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.

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

Again, how is that any different?

 

[Kitty]

So you don't think management strategies like pacing should be trialled?

No, because it's not a treatment and doesn't pretend to be. It's just resting the ankle you sprained yesterday.