Introduction
Recently in Vienna (Austria) an international conference has been taking place on Alzheimer's and Parkinson's Disease.
As I am unable to attend the conference in person I have been following the reports on Medscape (a news site for doctors and health professionals).
One particular report [1] relating to a poster presented by a Taiwanese team caught my attention.
They presented a poster which suggested that Metformin, one of the commonest drugs used to treat Type II diabetes mellitus (T2DM), may increase the risk of dementias.
This is frequently the kind of news that the media likes to cherry pick and create sensationalist headlines with.
As a result of that I wanted to briefly discuss these "findings" and caution against people reading too much into them.
It is very preliminary research and in view of that it needs to be taken in the appropriate context.
The Study
The study was presented in the form of a poster.
This is exactly what it sounds like - it is a large sheet (often made of card) which contains a summary of research.
Posters are often presented at conferences - they have a variety of uses but one of these is presenting early or preliminary research findings for discussion and commentary prior to being ready for publication.
For this reason the amount of information on view is limited compared to a formal paper.
According to the Medscape report which you can find here (but I'm not sure if it is accessible to non-clinicians) the group carried out a cohort study on 9300 patients with Type II diabetes (T2DM).
This means that people with T2DM were selected and followed up for a period of time to see if they developed a particular disease.
In this case they were followed up for up to 12 years to see if they developed Alzheimer's Disease (AD) or Parkinson's Disease (PD).
Of particular note from the figures reported are that the adjusted hazard ratio (HR) for all cause dementia was 1.66 in those taking metformin.
This means that those taking metformin were about 66% more likely to develop dementia than those not taking it.
The HR figures for specific causes were 2.27 for PD, 2.13 for AD and 2.30 vascular dementia.
The HR figures were also broken down against duration of treatment and seemed to show an increased risk the longer people were on metformin.
These figures seem to go against previous (also preliminary) research [2] which has suggested a neuroprotective effect from taking metformin.
Also if we look at conditions other than dementia, the current body of research on metformin has shown a whole host of benefits [3] including anti-ageing effects [4].
It is one of the most commonly prescribed drugs for Type II diabetes so it is likely that this will get a lot of publicity within the next few days (if it has not had it already).
Why We Should Not Read Too Much Into This
As I stated earlier this is preliminary research in the form of a poster.
We don't have enough information to ascertain exactly how the study was done.
The most important thing to look at in a study like this is methodology.
There are all sorts of confounding factors that need to be taken into account and may be skewing the data here.
How was account taken of these? Were they all taken into consideration? Without having the full data and methodology in a finished paper we cannot know.
Diabetes in itself is one of the major risk factors for dementias (particularly AD) - and if diabetes control/severity were not properly taken account of they could skew the results.
Further there may be other factors such as other diseases, medications, population characteristics (e.g. racial/genetic factors) and even geographic/environmental factors that may be skewing the results.
One of the most prominent confounding factors when it comes to metformin is that of nutritional status.
Due to the nature of T2DM it is commonly associated with sub-optimal diets. This makes sense given the strong association with problems such as obesity, blood lipid (fat) abnormalities etc. which comprise the so called "metabolic syndrome".
In addition to this, it has been known for several decades that metformin itself may have direct effects on nutrition that need to be controlled for and monitored.
For example it is known that metformin can cause a deficiency of Vitamin B12 in some patients [5,6]. For this reason it is wise to regularly monitor and if necessary supplement B12 levels in patients who are taking it - although this often does not occur due to a lack of awareness of this issue.
Could nutritional deficiencies such as this account for these results? Without seeing the complete study with the full data it is impossible to make such an assessment.
Even then it would need confirmation via repetition.
Conclusion
The important thing here is that these findings are preliminary information presented in the form of a poster.
They should be taken in this context and unless or until we get further information, they should not be reason for anxiety or changing medication/prescribing practices.
Right now we do know that uncontrolled T2DM poses a significant risk to health and that metformin is an effective means of treating and hence reducing those risks.
Until we have more definitive information it would be unwise to change current practices.
Thank you for reading
References
Kazemi, Khalil, Edward Unger, Diane Gartland, Crystal Hoecherl, Ruby Kevala, Ronald Johnstone, Mahadevane Saminadin, et al. 2017. “Metformin Linked to Dementia, Parkinson’s in Patients With T2DM.” Medscape. April 1. http://www.medscape.com/viewarticle/877965.
Gray, John, Ramanat Neelakantan, Keith Raymond, V. P. Gopinathan, Terry Lynch, H Robert Silverstein, Zsuzsanna Suba, et al. 2016. “Metformin Linked to Lower Neurodegenerative Disease Risk.” Medscape. June 15. http://www.medscape.com/viewarticle/864681.
Fujita, Yoshihito, and Nobuya Inagaki. 2017. “Metformin: New Preparations and Nonglycemic Benefits.” Current Diabetes Reports 17 (1): 5.
Anisimov, Vladimir N. 2013. “Metformin: Do We Finally Have an Anti-Aging Drug?” Cell Cycle 12 (22): 3483–89.
Kancherla, Vijaya, John L. Elliott Jr, Birju B. Patel, N. Wilson Holland, Theodore M. Johnson 2nd, Anjali Khakharia, Lawrence S. Phillips, Godfrey P. Oakley Jr, and Camille P. Vaughan. 2017. “Long-Term Metformin Therapy and Monitoring for Vitamin B12 Deficiency Among Older Veterans.” Journal of the American Geriatrics Society, February. doi:10.1111/jgs.14761.
Damião, Charbel Pereira, Amannda Oliveira Rodrigues, Maria Fernanda Miguens Castellar Pinheiro, Rubens Antunes da Cruz Filho, Gilberto Peres Cardoso, Giselle Fernandes Taboada, and Giovanna Aparecida Balarini Lima. 2016. “Prevalence of Vitamin B12 Deficiency in Type 2 Diabetic Patients Using Metformin: A Cross-Sectional Study.” Sao Paulo Medical Journal = Revista Paulista de Medicina 134 (6): 473–79.
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