Conference Coverage

DPPOS: Metformin showed no effect on cognition




SAN FRANCISCO – There appear to be no effects on cognition from participating in the lifestyle and metformin arms of the Diabetes Prevention Program Outcomes Study, results from a large long-term analysis showed.

Diabetes was not related to cognition, but a worse hemoglobin A1c level was associated with a worse cognitive performance, Dr. José A. Luchsinger said at the annual scientific sessions of the American Diabetes Association. "Importantly, metformin is safe from a cognitive standpoint, contrary to some recent reports."

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New data show that link between diabetes and cognition may not be very strong at all.

The Diabetes Prevention Program Outcomes Study (DPPOS) is a follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial that compared intensive lifestyle and metformin with placebo for the prevention of diabetes. On behalf of the DPP Research Group, Dr. Luchsinger presented findings from a study that set out to determine if the delay in or prevention of diabetes translated into cognitive benefits 12 years after randomization into the DPP.

"Diabetes in middle age and old age is related to cognitive impairment, both in amnestic and nonamnestic domains, and also in a range of severity from mild cognitive impairment to dementia," said Dr. Luchsinger of the department of medicine at Columbia University Medical Center, New York. "This association extends to the continuum of dysglycemia."

He and his associates hypothesized that diabetes prevention with metformin and lifestyle changes would be associated with better cognitive performance in the DPPOS. Their secondary hypotheses were that diabetes and dysglycemia are associated with worse cognitive function, and that metformin exposure is not associated with cognitive impairment. The researchers conducted cognitive assessments 12 and 14 years after DPP randomization. Global cognition was assessed with the six-item screener of the Mini-Mental State Exam, memory with the Spanish English Verbal Learning Test (SEVLT), and frontal executive function with an animal fluency (AF) and a letter fluency (LF) test and the Digit Symbol Substitution Test (DSST). They also calculated a composite of the SEVLT, AF, LF, and DSST results.

In all, 2,331 participated in the cognitive assessments. Their mean age was 64 years and 68% were women. There were no significant baseline differences in demographic and clinical characteristics by randomization group, but HbA1c level, diabetes prevalence, and diabetes duration were lower in the lifestyle and metformin groups.

Dr. Luchsinger reported that cognition was similar across all DPP treatment arms in year 8, while SEVLT improved from year 8 to year 10 in all arms (P = .0001). Changes in cognition were similar across DPP arms, but a worse HbA1c level was associated with a worse cognition composite score in models adjusted for age at randomization and assessment year (P = .0002). Exposure to metformin was not related to worse cognition.

"It’s important to consider that all DPP participants had impaired glucose tolerance at baseline," Dr. Luchsinger noted. "We had no people with normal glucose tolerance to compare them to; all had a high risk for developing diabetes. Also, the cohort is just entering the age of susceptibility of cognitive impairment. It may be that following them in older ages may show differences that we’re not seeing right now. A legacy effect is possible. By that I mean that there may be a long lag time from the intervention to cognitive effects."

The researchers plan to conduct a longer follow-up of the cohort with an assessment of brain structure function and amyloid load.

The study was supported by the National Institutes of Health, the Centers for Disease Control and Prevention, the Department of Veterans Affairs, the Indian Health Service, Bristol-Myers Squibb, Parke Davis, Lipha, and Lifescan. Dr. Luchsinger said he had no relevant financial conflicts.

On Twitter @dougbrunk

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