NCT04221750

Diet and Exercise Plus Metformin to Treat Frailty in Obese Seniors

Lifestyle Intervention Plus Metformin to Treat Frailty in Older Veterans With Obesity

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 114 (actual)
• Sponsor: VA Office of Research and Development · Federal
• Sex: All
• Age: 65 Years – 85 Years
• Healthy volunteers: Accepted

Summary

The continuing increase in prevalence of obesity in older adults including many older Veterans has become a major health concern. The clinical trial will test the central hypothesis that a multicomponent intervention consisting of lifestyle therapy (diet-induced weight loss and exercise training) plus metformin will be the most effective strategy for reversing sarcopenic obesity and frailty in older Veterans with obesity.

Detailed description

The growing prevalence of obesity in older adults including many older Veterans, has become a major concern in the US already strained health care system in general and in the VA in particular. In older adults, obesity exacerbates the age-related decline in physical function resulting in frailty, decrease in quality of life, loss of independence, and increase in nursing home admissions. The investigators' group demonstrated that weight loss from lifestyle therapy improves physical function and ameliorates frailty but the improvement was modest at best and most obese older adults remained frail. More importantly, there are concerns that the weight-loss induced loss of muscle and bone mass could worsen underlying age-related sarcopenia and osteopenia in the subset of frail obese elderly. Metformin, a biguanide, is a widely available drug used as first line treatment of type 2 diabetes. Animal studies suggest that metformin improves health span and increases lifespan, hence may represent a novel intervention for frailty. Because metformin reduces cellular senescence and senescence-associated phenotype (SASP), it is believed to retard accelerated aging most especially in older adults with obesity. The objective is to conduct a head-head comparative efficacy, placebo controlled, randomized controlled trial to test the hypothesis that lifestyle therapy + metformin for six months will be more effective than lifestyle therapy alone or metformin alone in improving physical function and preventing the weight loss-induced reduction in muscle and bone mass in obese (BMI \> 30 kg/m2) older (age 65 - 85 years) Veterans with physical frailty.

Conditions

• Frailty
• Sarcopenic Obesity
• Aging

Interventions

Type	Name	Description
BEHAVIORAL	Lifestyle therapy	Weight management program, in which participants are prescribed a balanced diet that provides and energy deficit of 500 to 750 kcal per day to induced \~10% weight loss plus Supervised combined aerobic and resistance exercise training three times weekly
DRUG	Metformin Hydrochloride	Given orally starting at 500 mg (one tablet) taken orally once a day with meals. After a week, the dose of metformin will be increased to 1000 mg (two tablets) daily. After another week, the dose of metformin will be increased to 1500 mg (three tablets) daily.
DRUG	Placebo	Given orally starting at 500 mg (one tablet) taken orally once a day with meals. After a week, the dose of placebo will be increased to 1000 mg (two tablets) daily. After another week, the dose of placebo will be increased to 1500 mg (three tablets) daily.
BEHAVIORAL	Healthy Lifestyle	Group educational sessions that focus on healthy diet, exercise, and social support once a month

Timeline

• Start date: 2021-05-14
• Primary completion: 2025-07-31
• Completion: 2025-07-31
• First posted: 2020-01-09
• Last updated: 2026-01-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study