Conference Coverage

Long-term metformin use protective against neurodegenerative disease




NEW ORLEANS – The use of metformin for at least 2 years had a protective effect on the incidence of neurodegenerative disease among elderly veterans, according to results from a large analysis of Veterans Affairs data.

At the annual scientific sessions of the American Diabetes Association, lead study author Qian Shi said that according to the current medical literature, diabetes increases one’s risk of Alzheimer’s disease (by 1.46- to 1.56-fold), all types of dementia (by 1.51- to 1.73-fold), vascular dementia (by 2.27- to 2.48-fold), and mild cognitive impairment (by 1.21-fold). “Metformin can cross the blood-brain barrier having specific effects on the central nervous system. But the exact mechanism and sites of its action remain unknown, and there are conflicting results,” said Ms. Shi, a PhD candidate in the department of global health policy and management at Tulane University School of Public Health and Tropical Medicine, New Orleans.

Qian Shi

Qian Shi

In an effort to examine the impact of receiving metformin treatment on the incidence of neurodegenerative disease and the association between length of metformin exposure and the risk of neurodegenerative diseases, the researchers used the Veterans Affairs database from 2004 to 2010 to study 6,046 patients who were at least 50 years of age with type 2 diabetes mellitus and were receiving long-term insulin treatment.

The length of metformin exposure was categorized by exposure years over the study period from baseline to the time of the first diagnosis of neurodegenerative disease, which included Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, dementia, and cognitive impairment. The five categories of metformin exposure time were no metformin treatment, less than 1 year, 1-2 years, 2-4 years, and 4 years or more. The mean age of patients was 63 years, 98% were male, and they were followed for a median of 5.3 years.

Of the 6,046 patients, 433 developed neurodegenerative disease during the study period, primarily dementia (334 cases). Other diagnoses included Parkinson’s disease (100 cases), Alzheimer’s disease (71 cases), and cognitive impairment (19 cases).

Ms. Shi reported that the adjusted incidence rates of neurodegenerative disease by cohort were 2.08 cases per 100 person-years for those who received no metformin treatment, 2.47 per 100 person-years for those treated with metformin for less than 1 year, 1.61 per 100 person-years for those treated 1-2 years, 1.30 per 100 person-years for those treated 2-4 years, and 0.49 person-years for those treated 4 years or more. The longer patients took metformin, the less likely they were to develop neurodegenerative disease, she said.

When comparing patients who received metformin treatment with those who did not on Cox regression analysis, the hazard ratio was 0.686 for neurodegenerative disease, 0.644 for dementia, and 0.611 for Parkinson’s disease. The risk reduction was not as robust for those with Alzheimer’s disease and cognitive impairment, most likely because of the limited number of cases, Ms. Shi said. Renal disease had no significant association with the risk of neurodegenerative disease, and it was balanced across metformin exposure groups.

She acknowledged certain limitations of the study, including its retrospective design, the high proportion of males, and the fact that data on diabetes duration and serum vitamin B level were not available.

The researchers reported having no relevant financial disclosures.

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