Diet and Exercise Plus Metformin to Treat Frailty in Obese Seniors

NCT ID: NCT04221750

Last Updated: 2026-01-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-14
• Study Completion Date: 2025-07-31

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Lifestyle Therapy plus Metformin

Diet-induced weight loss and Exercise Training plus Metformin 1500 mg daily

Group Type: EXPERIMENTAL

Lifestyle therapy

Intervention Type: BEHAVIORAL

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

Metformin Hydrochloride

Intervention Type: DRUG

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.

Lifestyle Therapy plus Placebo

Diet-induced weight loss and Exercise Training plus Placebo

Group Type: PLACEBO_COMPARATOR

Lifestyle therapy

Intervention Type: BEHAVIORAL

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

Placebo

Intervention Type: DRUG

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.

Healthy lifestyle plus Metformin

Healthy lifestyle and Metformin 1500 mg daily

Group Type: ACTIVE_COMPARATOR

Metformin Hydrochloride

Intervention Type: DRUG

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.

Healthy Lifestyle

Intervention Type: BEHAVIORAL

Group educational sessions that focus on healthy diet, exercise, and social support once a month

Interventions

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

Intervention Type: BEHAVIORAL

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.

Intervention Type: 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.

Intervention Type: DRUG

Healthy Lifestyle

Group educational sessions that focus on healthy diet, exercise, and social support once a month

Intervention Type: BEHAVIORAL

Other Intervention Names

Diet-induced weight loss and exercise training

Eligibility Criteria

Inclusion Criteria

• Age 65 - 85 years
• BMI = or > 30 kg/m2
• Mild to moderate frailty (score of 18 to 31 in the modified Physical Performance Test)
• Stable body weight (plus/minus 2 kg) during the past 6 months
• Sedentary (regular exercise <1 h/wk or <2 x/wk for the last 6 months)
• Willing to provide informed consent

Exclusion Criteria

• Any major chronic diseases, or any condition that would interfere with exercise or dietary restriction, or use of metformin, in which exercise, dietary restrictions, or metformin are contraindicated, or that would interfere with interpretation of results
• Cardiopulmonary disease (e.g. recent MI, unstable angina, stroke) or unstable disease (e.g., NYHA Class III or IV congestive heart failure, severe pulmonary disease requiring steroid pills or the use of supplemental oxygen) that would contraindicate exercise or dietary restriction
• Severe orthopedic (e.g. awaiting joint replacement) and/or neuromuscular (e.g. multiple sclerosis, active rheumatoid arthritis) disease or impairments that would contraindicate participation in exercise
• Renal impairment as defined by an estimated glomerular filtration rate (eGFR of less than 30 mL/min/1.73 m2) in which metformin is contraindicated
• Other significant co-morbid disease that would impair ability to participate in the exercise intervention (e.g. severe psychiatric disorder [e.g. bipolar, schizophrenia], excess alcohol use [>14 drinks per week])
• Severe visual or hearing impairments that would interfere with following directions
• Significant cognitive impairment, defined as a known diagnosis of dementia or positive screening test for dementia using the Mini-Mental State Exam (i.e. MMSE score <24)69
• Uncontrolled hypertension (BP>160/90 mm Hg)
• History of malignancy during the past 5 years (except non-melanoma skin cancers)
• Current use of bone acting drugs (e.g. use of estrogen, or androgen containing compound,raloxifene, calcitonin, parathyroid hormone during the past year or bisphosphonates during the last two years)
• Osteoporosis (T-score -2.5 and below on hip or spine scan) or history of fragility fractures
• Known history of diabetes mellitus or any of the following:
• Fasting blood glucose of 126 mg/dl, or HbA1c of 6.5% or >
• Terminal illness with life expectancy less than 12 months, as determined by a physician
• Use of any drugs or natural products designed to induce weight loss within past three months
• History of excessive alcohol consumption (e.g. 8 or more drinks a week for women and 15 or more drinks a week for men)
• Positive exercise stress test for ischemia or any indication for early termination of exercise stress testing
• Taking metformin or any other glucose lowering drug
• Lives outside of the study site or is planning to move out of the area in the next 2 years

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Michael E. DeBakey VA Medical Center

FED

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: collaborator

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dennis T Villareal, MD

Role: PRINCIPAL_INVESTIGATOR

Michael E. DeBakey VA Medical Center, Houston, TX

Locations

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

H-46970

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ENDA-007-19F

Identifier Type: -

Identifier Source: org_study_id