African American patients with type 2 diabetes taking metformin showed a substantial reduction in risk for dementia compared with similar patients started on a sulfonylurea; this effect was particularly evident among those in the 50 to mid-60s age bracket.
And the effect was far less marked in white patients, according to a new, large retrospective study of Veterans Health Administration data.
Middle-aged African American patients (50-64 years) taking metformin showed a 40% risk reduction, while those aged 65-74 years showed a 29% lower risk of dementia compared with similar patients taking a sulfonylurea. White patients, meanwhile, only showed around a 4% risk reduction on metformin compared with sulfonylureas.
"Based on our evidence, this reduced risk is not a result of glycemic control but could be due to metformin's potential to reduce risk of vascular events as well as vascular dementia," lead author Jeffrey Scherrer, PhD, from Saint Louis University School of Medicine, Missouri, told Medscape Medical News.
Scherrer, who is also with the Harry S. Truman Veterans Administration Medical Center, Columbia, Missouri, speculates that metformin might reduce systemic inflammation; the latter is a consequence of diabetes that occurs more commonly in African American patients, he said.
He noted the large treatment effect observed in black patients, which he said is "unusual" given the large sample size. Calling the findings "remarkable," he said they may point to a novel approach with a cheap drug for reducing the risk of dementia in African Americans with type 2 diabetes.
"If there's a concern about dementia, metformin is a safe drug that could potentially be started earlier, however, replication of these results is needed," he stressed to Medscape Medical News. The study was published in the July/August issue of Annals of Family Medicine.
African Americans Have Higher Rates of Type 2 Diabetes and Dementia
Prior evidence from observational studies has suggested metformin, compared with sulfonylureas, is associated with an 8% to 10% decrease in dementia risk, say the researchers.
Scherrer, who is an epidemiologist, said he and his colleagues wanted to evaluate race differences associated with the effect of metformin on dementia, because of the higher prevalence of dementia in African Americans and the consequences of type 2 diabetes on dementia risk, which are greater in blacks than whites.
They studied 73,761 African American and white patients aged 50 years or older from the Veterans Health Administration database. At study start, patients were free of dementia and were naive to diabetes medications, other than starting on metformin or a sulfonylurea monotherapy.
Incidence of dementia was determined by diagnostic code; mild cognitive impairment was not included.
Metformin's Protective Effect Appears Independent of Glycemic Control
Over a mean follow-up of around 6.5 years, regardless of age, the African American participants showed a greater than 25% lower risk of dementia if they took metformin compared with a sulfonylurea (hazard ratio [HR], 0.73; 95% CI, 0.6 - 0.89).
In contrast, white patients had just a 4% to 8% lower risk (HR, 0.96; 95% CI, 0.9 - 1.03), he noted in an interview with Medscape Medical News.
"Importantly, in addition to the baseline balancing of variables, we controlled for the duration of time spent in a hypoglycemic state after medication start. We still arrived at the same result, so the findings are independent of glycemic control."
The team also adjusted for a wide range of confounding variables, including ischemic heart disease, stroke, hypertension, diabetes complications, and HbA1c, as well as psychiatric disorders, alcohol dependence, illicit drug abuse, and nicotine dependence/smoking.
When stratified further by age group, in African Americans aged 50-64 years, dementia risk was reduced (HR, 0.60; 95% CI, 0.45 - 0.81). This effect was not seen among white patients in the same age group (HR, 0.94; 95% CI, 0.81 - 1.09).
In the 65-74 years age bracket of white patients, there appeared to be a 10% lower risk of dementia on metformin compared with a sulfonylurea (HR, 0.90; 95% CI, 0.82 - 0.99), a result that confirmed findings of a prior study, said Scherrer.
In African Americans of the same age, dementia risk was reduced by around 29% (HR, 0.71; 95% CI, 0.53 - 0.94).
Notable Protective Effects of Metformin in African Americans
"What I think is remarkable...is the over 40% reduced risk in African Americans [50-64 years of age] on metformin, and around a 29% lower risk in the 65-74 years age group," emphasized Scherrer.
"It's not a surprise that the oldest patients [75 years plus] have reduced benefit because there are so many other risk factors for dementia at this age and less opportunity for metformin's protective relationship with dementia to take effect."
"What is strange is why is metformin causing a protective effect in African Americans? Given we know they have worse glycemic control and more diabetes-related adverse events, what else does metformin do that might be relevant here?"
Reflecting on the potential mechanisms, Scherrer said that the drug could be working by reducing systemic inflammation.
"This finding is a large effect, which is unusual to find in such a large sample. This is atypical," he observed.
He and his colleagues concluded: "There are no existing medications to prevent dementia." The current findings "suggest that someday this inexpensive, widely available treatment could be broadly prescribed to substantially reduce the risk of dementia in younger African American patients with type 2 diabetes."
Scherrer has reported no relevant financial relationships.
Ann Fam Med. 2019;17:352-362. Full text
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Cite this: Could Cheap Drug Metformin Prevent Dementia in Black Patients? - Medscape - Jul 19, 2019.