Combination therapy shows promise in reversing frailty in older veterans

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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