Does metformin have long term side effects?

What the evidence says

Metformin is the medicine doctors usually try first for type 2 diabetes, and it has a long track record of being safe. Diabetes Canada notes that metformin has a relatively mild side effect profile and a strong long-term safety record compared to other diabetes drugs.

The most common side effects, like nausea, diarrhea, and stomach discomfort, happen early and usually fade within one to two weeks as the body adjusts, and taking the pill with food or starting at a low dose helps.

The main long-term concern is vitamin B12. Studies, including a 13-year follow-up of a large clinical trial, found that people who took metformin for many years were more likely to develop low B12 levels and mild anemia than those who did not. Low B12 can, in rare cases, cause nerve damage or worsen memory problems if it goes unnoticed for a long time, so some doctors check B12 levels periodically in people on metformin for years, especially if they eat little meat or dairy.

A much rarer but more serious long-term risk is a condition called lactic acidosis, a buildup of acid in the blood. This mainly affects people with significant kidney disease, liver disease, heavy alcohol use, or heart failure, which is why kidney function is usually checked regularly while on metformin.

On the other side, some long-term studies suggest metformin may help with weight and possibly support brain health over time, though this evidence is less certain and comes mostly from observational research rather than large trials designed to test that question directly.