Megan Brooks

July 16, 2013

BOSTON, Massachusetts — Type 2 diabetes doubles the risk for dementia, and a large new observational study suggests that treatment with metformin may significantly lower that risk. In contrast, other diabetes treatments, including insulin, were associated with increased dementia risk.

"These results provide preliminary evidence that the benefits of insulin sensitizers may extend beyond glycemic control to neurocognitive health," said Rachel Whitmer, PhD, senior scientist at the Kaiser Permanente Northern California Division of Research, Oakland.

The results build on a "nice line of evidence" from animal models and cell culture studies showing that metformin might be neuroprotective by promoting neurogenesis and ameliorating neuronal insulin resistance.

Dr. Whitmer presented her group's findings here at the Alzheimer's Association International Conference (AAIC) 2013.

New Users

For this report, researchers studied a cohort of 14,891 patients with type 2 diabetes age 55 years and older who began diabetes therapy between October 1999 and November 2001. In this "new user" cohort, only patients who started a single drug (metformin, sulfonylureas [SU], thiazolidinediones [TZDs], or insulin) were included.

During 5 years of follow-up, dementia was diagnosed in 1487 (9.9%) patients.

Compared with patients starting SU, those starting metformin had about a 20% reduced risk for dementia (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.65 - 0.95), Dr. Whitmer reported.

Compared with patients starting TZD, those starting metformin had a 23% lower risk for dementia during follow-up (HR, 0.77; 95% CI, 0.66 - 0.90).

In contrast, starting SU (compared with metformin) was associated with a 24% increased risk for dementia (HR, 1.24, 95% CI, 1.1 - 1.4); TZD, an 18% increased risk (HR, 1.18; 95% CI, 1.1 - 1.4); and insulin, a 28% increased risk (HR, 1.28; 95% CI, 1.1 - 1.6).

The results were the same after the researchers took into account diabetes duration, age, and glycemic control and when they considered dementia subtypes. The findings provide "preliminary evidence that metformin may have benefits on brain health," Dr. Whitmer said.

Diabetes and Dementia

David S. Knopman, MD, from the Mayo Clinic, Rochester, Minnesota, who moderated a press briefing on this topic, noted that the relationship between diabetes and the development of dementia has generated "great interest" in the scientific community.

This type of epidemiologic study, he noted, is intended to "generate hypotheses that can be tested in proper therapeutic trials." The findings from Dr. Whitmer's group suggest a rationale for doing such a trial. Indeed, trials are underway to evaluate metformin as a potential therapeutic agent for mild cognitive impairment and dementia.

The study was funded by Kaiser Community Benefits and the National Institute of Diabetes and Digestive and Kidney Diseases. The authors have disclosed no relevant financial relationships.

Alzheimer's Association International Conference (AAIC) 2013. Oral Presentation: O1-05-05. Presented July 15, 2013.

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