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Placebo response needs to be ruled out with RCT

Posted by sspaulding on 15 May 2019 at 17:47 GMT

I hope that metformin and other anti-IR drugs are effective in Fibromyalgia. However, I doubt the pain scales results.
I suspect that if you did a RCT, you would see less miraculous reductions in pain.

Another problem is the pathogenesis of fibromyalgia (hypothesized to be due to IR) is one thing, development of higher BMI due to the inability to exercise without increasing pain, is another.

How many of the 16 patients (out of 23 total) who consented to take metformin, had lab confirmed small vessel neuropathy?

How long had the fibromyalgia patients had fibromyalgia, and how long had they had elevated (or elevated per age controls) HbA1C ? Is the potential for pain reduction higher in patients with long-standing IR ?

No competing interests declared.
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RE: Placebo response needs to be ruled out with RCT

MikePappolla replied to sspaulding on 16 May 2019 at 19:35 GMT

These are all interesting questions. Please read the discussion section of our paper, as some of these are already addressed in this section. The marked degree of analgesia observed in our population may reflect the synergistic effect between metformin and other drugs used as “standard treatment”, as indicated in the paper (rather than the effect of metformin alone). The degree of therapeutic response to metformin monotherapy is probably of lesser magnitude will have to be determined in future trials.

We do not have information on the incidence of small fiber neuropathy in the patients included in the study. Most of the patients included in this study were unaware of having an abnormal HbA1c value prior to the first encounter and laboratory work up performed at the clinic; therefore, it is not possible to determine the length of time they were affected by such abnormal values. It is important to recognize that the HbA1c values in a substantive number of the patients studied were either considered normal by the current American Diabetes Association criteria or were only minimally elevated. However, these values were distinct from those occurring in two normal control populations as determined by statistical means after age adjustments were performed. Pertaining to the duration of the symptoms, they all exceeded a minimum of three months (we would have to re-review the records to provide you with a more accurate answer).

Regarding the magnitude of the therapeutic response, we anticipate that the best outcomes are likely to be observed with early treatment of insulin resistance. This is speculative at this time and inferred from what occurs in (large fiber) diabetic neuropathies (unrelated to fibromyalgia) where the progression of the pathology can be arrested only if patients are treated sufficiently early during the pre-diabetes stage (up to 40% of large fiber peripheral neuropathies developed during pre-diabetes).

Often, more questions than answers are usually engendered by a new discovery and hope that further research will be pursued as a result of these very preliminary findings.

We appreciate for your interest in our study.

M. A. Pappolla (www.smpsclinic.com)

Competing interests declared: M. A. Pappolla filed a provisional patent application with the USPTO (number 62798828). Title: “Formulations and Methods for Treatment of Fibromyalgia and Related Myofascial Pain Disorders”. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors have nothing to declare.
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