Is stopping metformin therapy linked with dementia risk?

By Melanie Hinze

New research suggests that stopping metformin therapy might be linked with dementia incidence, largely independent of changes in glucose control or insulin use.

Published in JAMA Network Open, the cohort study looked at metformin users born before 1955 and who had no history of kidney disease at metformin initiation from a large integrated healthcare delivery system in Northern California. Dementia follow up took place from 1996 through to 2020, with data analysis from 2021 to 2023.

Overall, 12,220 early terminators of metformin (46.2% female; mean age at first metformin prescription 59.4 years) were matched with 29,126 routine metformin users of the same age and gender who had diabetes for the same duration. Early terminators were defined as individuals who stopped metformin with normal estimated glomerular filtration rate (eGFR). Routine users had not yet terminated metformin or had terminated metformin after their first abnormal eGFR measurement.

The researchers found that early terminators were 21% more likely to be diagnosed with dementia during follow up than routine users of metformin (hazard ratio, 1.21 95% confi­dence interval 1.12–1.30). This association was largely independent of changes in HbA_1c level and insulin usage.

Associate Professor Ryu Takechi, Director of the Curtin Health Innovation Research Institute (CHIRI) and Domain Lead for Neurodegeneration and Chronic Pain Research in Perth, told Medicine Today this was an interesting study that was unique in that it looked at individuals who stopped taking metformin in the context of dementia risk, rather than comparing metformin users versus nonusers.

‘This study per se supports the notion that metformin may be beneficial in preventing dementia in patients with diabetes,’ he said, but added that in the context of other research, it was still inconclusive and emphasised the need for further research.

‘In my opinion, it is prema­ture to say that metformin use will significantly decrease the dementia risk,’ he said.

Associate Professor Takechi added that this research was a good reminder that diabetes increases the risk of cognitive decline and dementia, and that it was important to start implementing some preventative strategies as early as possible.

‘A body of literature does report that cognitive decline develops even in patients with well­controlled diabetes,’ he added.

JAMA Network Open 2023; 6: e2339723; doi:10.1001/jamanetworkopen.2023.39723.