Metformin added to lifestyle intervention for physical function in older adults with obesity (DEMFOS trial): a randomised controlled trial.
In older adults with obesity, adding metformin to an intensive lifestyle intervention does not significantly improve physical function compared to placebo.
Where it sits
this study against the rest of the cjc-1295 corpusSummary and findings
This study evaluated the effect of metformin added to an intensive lifestyle intervention on physical function in older adults with obesity. The trial included 114 participants aged 65-85 years. No significant improvement in physical function was observed with metformin compared to placebo.
Abstract
<h4>Background</h4>Obesity in older adults is associated with functional decline and increased risk of disability. Lifestyle interventions improve physical function, but the role of metformin as an adjunct to lifestyle intervention in this population remains unclear. In this randomised clinical trial, we evaluated whether metformin enhances the effects of an intensive lifestyle intervention on physical function in older adults with obesity.<h4>Methods</h4>The Diet and Exercise plus Metformin to Treat Frailty in Obese Seniors (DEMFOS) trial (ClinicalTrials.gov: NCT04221750 [completed]) was a randomised, placebo-controlled trial conducted at the Michael E DeBakey Veterans Affairs Medical Center and Baylor College of Medicine (Houston, TX, USA). Older adults (aged 65-85 years) with obesity (BMI ≥30 kg/m<sup>2</sup>) were randomly assigned to intensive lifestyle intervention (weight-management and exercise training) plus placebo, intensive lifestyle intervention plus metformin, or healthy lifestyle (diet education) plus metformin groups. The primary outcome was change in the modified physical performance test score at 6 months. The primary analysis was by intention-to-treat.<h4>Findings</h4>Of 221 participants assessed for eligibility between March 30, 2021, and Dec 12, 2024, 114 were included in this study (mean age 72·8 years [SD 5·2]; 101 [89%] men and 13 [11%] women). 64 (56%) participants were White, 50 (44%) were Black, and 15 (13%) were Hispanic or Latino. Changes in physical performance test differed between groups (group-by-time interaction p<0·0001). At 6 months, physical performance test improvement was greater in the intensive lifestyle plus metformin group than in the healthy lifestyle plus metformin group (mean difference 2·5 points, 95% CI 1·2-3·8; p=0·0002), whereas there was no difference between the intensive lifestyle plus metformin and intensive lifestyle plus placebo groups (0·1 points, -1·2 to 1·4; p=0·92). Serious adverse events were infrequent and not attributed to the study interventions.<h4>Interpretation</h4>Our findings suggest that in older adults with obesity undergoing intensive lifestyle intervention, metformin does not provide additional improvement in physical function. These results support prioritising lifestyle-based strategies to improve functional outcomes in this population.<h4>Funding</h4>US Department of Veterans Affairs.
Background
This paper addresses the impact of metformin as an adjunct to lifestyle interventions on physical function in older adults with obesity. Previous research has indicated that lifestyle interventions can improve physical function, but the specific role of metformin remains unclear. Understanding whether metformin enhances these interventions is crucial for developing effective strategies for this population.
Methods
The DEMFOS trial was a randomised, placebo-controlled trial involving older adults aged 65-85 years with obesity (BMI ≥30 kg/m²). Participants were randomly assigned to one of three groups: intensive lifestyle intervention plus placebo, intensive lifestyle intervention plus metformin, or healthy lifestyle plus metformin. The primary outcome was the change in the modified physical performance test score at 6 months, with an intention-to-treat analysis.
Results
At 6 months, the primary endpoint showed that the physical performance test improvement was greater in the intensive lifestyle plus metformin group compared to the healthy lifestyle plus metformin group, with a mean difference of 2·5 points (95% CI 1·2-3·8; p=0·0002). However, there was no significant difference between the intensive lifestyle plus metformin and intensive lifestyle plus placebo groups (0·1 points, -1·2 to 1·4; p=0·92).
Interpretation
The findings suggest that while metformin may enhance the effects of lifestyle interventions compared to a healthy lifestyle alone, it does not provide additional benefits over placebo when combined with intensive lifestyle interventions. The effect size observed in the comparison between metformin and placebo was negligible, indicating limited clinical significance. The study's limitations, including a small sample size and short follow-up duration, may affect the generalizability of the results.
Key findings
- At 6 months, physical performance test improvement was greater in the intensive lifestyle plus metformin group than in the healthy lifestyle plus metformin group (mean difference 2·5 points, 95% CI 1·2-3·8; p=0·0002)
- There was no difference between the intensive lifestyle plus metformin and intensive lifestyle plus placebo groups (0·1 points, -1·2 to 1·4; p=0·92)
- Of 221 participants assessed for eligibility, 114 were included in this study (mean age 72·8 years [SD 5·2]; 101 [89%] men and 13 [11%] women)
- 64 (56%) participants were White, 50 (44%) were Black, and 15 (13%) were Hispanic or Latino
- Serious adverse events were infrequent and not attributed to the study interventions
Limitations
- small sample size (n=114)
- only 6-month follow-up
- specific population may limit generalizability
- no significant clinical improvement observed