Metformin linked with lower delirium risk in older patients with type 2 diabetes

Metformin use is associated with a lower risk of delirium in older adults with type 2 diabetes, with higher doses of the drug offering greater protection, a matched cohort study in Taiwan found.

Researchers used a national health insurance database to identify individuals who were at least 65 years of age and had type 2 diabetes between January 2008 and December 2019. Patients were divided into metformin users and an active comparator group (66,568 in each arm; mean age, 77.7 years) and followed until December 2021. Those in the metformin group consistently used the drug as their primary antidiabetic therapy throughout the study period. The researchers defined diabetes-related delirium as delirium that developed in type 2 diabetes patients, was diagnosed after diabetes onset, and required hospitalization. Any patient with prior dementia or major cranial events was excluded from the study. Findings were published by Diabetes Care on Oct. 3.

Incidence of delirium and all-cause mortality was significantly lower in the metformin group than in the comparator group (2.2% vs. 3.6% and 7.2% vs. 11.3%, respectively; P<0.0001 for both comparisons). Adjusted analyses showed metformin was linked to a significantly lower risk of delirium, with adjusted hazard ratios (HRs) ranging from 0.77 to 0.81 (P<0.0001). In a competing risk analysis that accounted for potential bias from competing risks of death, adjusted HRs ranged from 0.81 to 0.84 (P<0.0001) . Risk of all-cause mortality was also significantly lower in the metformin group (adjusted HRs, 0.59 to 0.62; P<0.0001). A dose-response relationship was observed, with higher cumulative and daily doses of metformin associated with greater reductions in delirium risk. For the highest quartile of cumulative defined daily doses, the adjusted HR for delirium was 0.53 (95% CI, 0.46 to 0.61; P<0.0001) compared with 0.96 (95% CI, 0.87 to 1.07; P=0.4585) in the lowest quartile.

Limitations to the study include its observational design and reliance on administrative data. The researchers cautioned that the findings alone do not support routine use of metformin as a preventive measure against cognitive decline and recommended additional prospective controlled studies to investigate this association.

“Our study results suggest that metformin not only provides metabolic benefits but also offers significant protective effects against cognitive decline, underscoring its potential to improve long-term outcomes and quality of life for older adults with [type 2 diabetes],” they concluded.