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Geroprotective effects of diet and exercise plus metformin in frail older veterans with obesity: The DEMFOS
Nina Klonis1, Maria Liza Nava Duremdes1, Marlene Aguilar1
1Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center, Houston, TX, USA; Division of Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, Houston, TX, USA.
Background:
Frailty and obesity frequently coexist in older adults, particularly among Veterans, contributing to loss of independence, physical disability, and increased healthcare utilization. Lifestyle interventions improve mobility and function but often lead to loss of lean mass and bone density. Metformin, a widely used antidiabetic agent with geroprotective properties, may mitigate these adverse effects by targeting cellular mechanisms of aging.
Objective:
To determine whether adding metformin to lifestyle therapy (diet-induced weight loss and supervised multicomponent exercise) improves physical function and musculoskeletal health, compared with lifestyle therapy alone and with a healthy-lifestyle program combined with metformin.
Design:
Six-month, randomized, double-blind, placebo-controlled, three-arm clinical trial.
Setting And Participants:
Conducted at the Michael E. DeBakey VA Medical Center (Houston, TX) in 114 older Veterans (aged 65-85 years) with obesity (BMI ≥30 kg/m2) and mild-to-moderate frailty (Physical Performance Test [PPT] 18-31).
Interventions:
Participants are randomized to (1) Lifestyle Therapy + Metformin, (2) Lifestyle Therapy + Placebo, or (3) Healthy Lifestyle + Metformin. The lifestyle intervention includes dietary counseling targeting a 500-750 kcal/day deficit and supervised aerobic and resistance exercise three times per week. Metformin or placebo is titrated to 1500 mg daily and dispensed under blinded conditions.
Primary Outcome:
Change in PPT score from baseline to 6 months.
Conclusion:
The Diet and Exercise plus Metformin to Treat Frailty in Obese Seniors (DEMFOS) study evaluates whether combining lifestyle therapy with a pharmacologic aging modulator can improve function and musculoskeletal integrity beyond either intervention alone, addressing a critical need in geriatric obesity care.
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