Metformin inhibits mTOR signalling pathway which helps with its anti-cancer properties. Blocking mTOR also seems to reduce tolerance. Tolerance can be seen in tissue lines by elevated nitrite levels. Metformin prevent nitrite elevation with both methadone and morphine.
I don’t know why actually studies in diabetics on metformin re opioids have not been done but implications from basic science suggests it might be helpful in preventing tolerance,
J Cell Physiol. 2018 Aug 26. doi: 10.1002/jcp.27125. [Epub ahead of print]
In vitro evaluation of effects of metformin on morphine and methadone tolerance
through mammalian target of rapamycin signaling pathway.
Shirooie S et al
It is mind numbing to go over all the tables but what I got out ot it included:
- signs of tolerance at much less with methadone
- metformin pre-treatment prevented tissue nitrite elevations that are signs of opioid tolerance