The CEO of Diabetes In Control read about this and found it fascinating as have a lot of people. We reached out to members of our advisory board and asked:
Your patients may have asked about it or, if not yet, they most likely will. What is your comment on whether you recommend metformin for people who do not have diabetes? If you do not, how do you respond to patients who ask about it? If you do, what do you tell your patients? And what do you say to your patients when their other health care providers tell them this is a diabetes drug and they should only be taking it if they have diabetes?
Here’s the comments we have received thus far:
Just like with most medications, there are good and bad side effects in using metformin. I have patients who complain of bad news and those who hear positive news. Recently, the news on metformin has been more positive. From anticancer to effects on telomere length, there are great reasons to consider dedicated clinical trials using metformin in answering specific questions. A year ago, it was a different story. Who knows where we will be five years from now.
As far as recommendations for metformin use in non-diabetic people, there is too much unknown about long-term outcomes to be broadly using metformin as an anticancer or longevity enhancing drug. There is more health promoting effects of healthy eating and an active lifestyle.
Sorry, there is no shortcut! (Yet)!!!
The situations where I recommend metformin in people without diabetes are the following:
In young women with polycystic ovarian disease and obesity, metformin is a fairly standard routine of care by obstetricians, physicians, and endocrinologists in India who believe it helps in reducing the symptoms of PCOS. It helps to normalize the menstrual cycles and also helps to some extent in weight reduction.
The other situation where I recommend metformin is in people with prediabetes who also have a family history of diabetes and therefore are at great risk of converting to diabetes. Undoubtedly, lifestyle modification, diet and exercise, and weight reduction are much more powerful, but in some individuals, particularly in those with impaired glucose tolerance, metformin works well. Apart from these two situations, I do not use metformin purely as a weight reduction tool in those who have normal glucose tolerance.
Unlike western countries, people in India are not so much aware about metformin and there is a general tendency for people to try to avoid taking drugs wherever possible and to try lifestyle modification. So, we do not face this problem quite often. However, among the people of higher socio-economic strata who are also literate, occasionally we may get these questions. In such situations, we discuss the pros and cons with the patient. As I said earlier, if they have either impaired glucose tolerance or PCOS, then we generally settle for using for metformin. Otherwise we discourage them from using the same.
Regarding prescribing anti-cancer or anti-aging, I would not use it. We will have to wait until we have more data, particularly long-term data. We all know that metformin is not entirely without side effects. It can have gastrointestinal side effects like bloating and diarrhea in quite a few people apart from the very small risk of lactic acidosis.
Our current logic for the pathophysiology of diabetes, its complications, and other conditions with overlapping genes and pathophysiologies (see slides) implies that many agents for diabetes may, and can be, repurposed to treat the related conditions; this logic presumably can apply whether the patient has diabetes or not.
For example, data is available on the effectiveness of using metformin or pioglitazone to treat NASH; similarly, reports suggest efficacy of the use of pioglitazone to treat psoriasis, whether having diabetes or not.
Similarly, there are data that suggest dementia is reduced in patients with diabetes who happen to be on metformin, and studies in vitro and in rodents suggest possible mechanisms for why it might have that beneficial effect. No evidence is available in non-diabetic patients, but our construct logic suggests it is possible.
Also, biochemical mechanisms are described for the logic of using metformin for prevention/treatment of cancer. (See attached pictures, though data is sparse.)
Thus, in an evidence-based PRACTICE mode of clinical care, I occasionally use metformin in the treatment of NASH, whether they have diabetes or not.
In a patient without diabetes who asks regarding treatment with metformin to obviate cancer or dementia, I would not be adverse to trying it, especially if I could clinically discern that they have evidence of pathophysiologic mechanisms existing in each individual patient for any of the genes or other pathophysiologic mechanisms that could be addressed by metformin — inflammation, insulin resistance, environmental risks, fuel excess (obesity), and family history of diabetes and cancer or diabetes and dementia. Obviously, one would alert the patient to its ‘off-label ‘ use, and not use it if the patient had renal insufficiency per current guidelines.
Certainly this approach will be easier when we have accepted markers (genomic and epigenomic chips, metabolomic and proteomic chips) that would suggest metformin (and other meds for diabetes) would benefit. Clearly, our model, at a minimum, suggests where future research might be aimed.
To you, our members, how do you respond to these questions? Please send your responses to: firstname.lastname@example.org