Whatever happened to metformin for PD?

[drumhead]

It seemed as though researchers had identified metformin as a potential disease modifying drug for PD a few years back but I haven't heard anything about it recently. Anyone know what happened? Did further research not support its use? Is it too cheap so big pharma doesn't want to research further?

pmc.ncbi.nlm.nih.gov/articl...

[Boscoejean]

"Long-term use of metformin reduces BDNF transcription and inhibits nuclear factor E2-related factor 2 (Nrf2), which may increase the vulnerability of the central nervous system. Some studies have also suggested that metformin increases the risk of PD or even aggravates neuronal damage."

journals.lww.com/jbioxresea....

link.springer.com/article/1....

"Metformin may have a beneficial effect on PD neuropathology. The neuroprotective effect of metformin is mainly mediated by activating adenosine monophosphate protein kinase (AMPK), which reduces mitochondrial dysfunction, oxidative stress, and α-synuclein aggregation. As well, metformin mitigates brain IR a hallmark of PD and other neurodegenerative diseases. However, metformin may harm PD neuropathology by inducing hyperhomocysteinemia and deficiency of folate and B12. Therefore, this review aimed to find the potential role of metformin regarding its protective and detrimental effects on the pathogenesis of PD. "

[JayPwP in reply to Boscoejean]

😀😀😀😀

So research supporting both sides?

[MarionP in reply to JayPwP]

That's actually what you want to see in science, evidence-based result without regard into anything but their actual results. It seems almost entirely unheard of these days to see results that do not support the prospects of a company's product, primarily because it is very much in the opposite direction of their hopes and investments and business plans. It's a hidden but well-known scandal among scientists and researchers, if you want to have a career you have to post "positive" direction results or you stop being employed and published. If you work for a company producing a product, releasing any negative results that you obtained is a fast track to the unemployment line and everybody from investors to marketers to potential customers and business clients become as extinct as the dodo bird and carrier pigeon. You do not pass Go. You become Wally Pipp.

[AkunaMatata]

Metformin use is associated with a higher risk of PD in most longitudinal studies.

[BlockRuys in reply to AkunaMatata]

Such as?

[AkunaMatata in reply to BlockRuys]

alzres.biomedcentral.com/ar...

“A systematic review and meta-analysis of observational studies testing the association between metformin and neurodegenerative diseases analysing a total of 19 studies with 285,966 participants found no association between metformin exposure and incidence of all subtypes of neurodegenerative diseases, and found that metformin monotherapy was associated with an increased incidence of PD compared to non-metformin or glitazone users”

drc.bmj.com/content/8/1/e00...

“Meta-analysis found there was no significant effect on incidence of all the subtypes of NDs with metformin exposure (OR 1.04, 95% CI 0.92 to 1.17). However, **metformin monotherapy was associated with a significantly increased risk of PD incidence** compared with non-metformin users or glitazone users (OR 1.66, 95% CI 1.14 to 2.42).”

“Subgroup analysis showed metformin exposure increased the risk of Parkinson disease (PD) by 66% (OR 1.66, 95% CI 1.14 to 2.42).”

The issue might be high dose and/or long-term treatment:

pmc.ncbi.nlm.nih.gov/articl...

“Metformin was associated with PD odds in T2DM in a dose–response association manner. Patients who received low dosage and intensity of metformin use were associated with lower odds of PD, while higher dosage and intensity of metformin use had no neuroprotective effect.”

nature.com/articles/s41398-... ("Reconsidering repurposing: long-term metformin treatment impairs cognition in Alzheimer’s model mice")

pmc.ncbi.nlm.nih.gov/articl...

“controversial results obtained both in experimental models and in clinical studies”

“Therefore, it is necessary to understand the precise metformin dosage necessary to alter the AMP/ATP ratio and activate AMPK, without the induction of detrimental effects.”

“At the same time, the prolonged consumption of metformin at a relatively high dosage might induce serious side effects that could worsen the risk of developing PD over time.”

medscape.com/viewarticle/87...

----------

That's just a few. In people with diabetes, SGLT2 inhibitors users have a way lower rate of PD vs metformin users. Not sure if it's causal though.