October 24, 2023Psychosomatic Medicine6 citationsOpen Access

Depression, Inflammation, and the Moderating Role of Metformin: Results From the Midlife in the United States Study and Sacramento Area Latino Study on Aging

SSSumaiyah SyedSouthern Methodist University JCJared Isaac CortezThe University of Texas at Dallas SWStephanie J. WilsonUniversity of Alabama at Birmingham

Structured PICO

Does metformin use buffer the association between depressive symptoms and inflammatory markers in middle-aged and older adults?

Population

3,041 middle-aged and older adults, comprising 1,255 primarily White adults from the Midlife in the United States Study and 1,786 older Latino adults from the Sacramento Area Latino Study on Aging

Intervention

Metformin use

Comparator

Metformin nonusers

Outcome

Association between depressive symptoms and inflammatory markers (interleukin 6 [IL-6], tumor necrosis factor α, and C-reactive protein [CRP])surrogate

Metformin use may attenuate the association between depressive symptoms and systemic inflammation in primarily White adults, though this potential anti-aging benefit was not observed in older Mexican Americans.

Abstract

OBJECTIVE: Depression can promote inflammation and accelerate aging. Metformin, a widely prescribed antidiabetic, has shown promising preclinical evidence of aging-related health benefits, including decreased inflammation. The current study examined whether metformin usage buffers the association between depressive symptoms and inflammatory markers in two large samples of middle-aged and older, primarily White adults, and older Latino adults. METHODS: Data from the Midlife in the United States Study ( N = 1255) and the Sacramento Area Latino Study on Aging ( N = 1786) included information on medication use, depressive symptoms, and inflammatory markers, namely, interleukin 6 (IL-6), tumor necrosis factor α, and C-reactive protein (CRP). These data were merged into a harmonized sample, and the sample group variable was included in a three-way interaction for analysis. RESULTS: Specifically, in the Midlife in the United States Study sample, metformin buffered the association between depressive symptoms and CRP ( b = -0.029, standard error SE = 0.013, p = .007) and IL-6 ( b = 0.21, SE = 0.010, p = .046), whereas no significant association was found with tumor necrosis factor α. Metformin nonusers displayed higher depressive symptoms associated with elevated CRP ( b = 0.01, SE = 0.003, p .068). Conversely, in the Sacramento Area Latino Study on Aging sample, metformin use did not show a significant protective link. CONCLUSIONS: Results from mostly White, highly educated adults supported a mitigating role of metformin in ties between depression, a well-known behavioral risk factor, and inflammation, a key source of biological aging. However, the benefits did not extend to a large sample of older Mexican Americans. The findings reveal a hidden potential benefit of this therapeutic agent and raise important questions around its health equity. TRIAL REGISTRATION: The study was preregistered on OSF ( https://osf.io/c92vw/ ).

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