Can metformin prevent worsening of muscle weakness and frailty in older people who are showing early signs of frailty?

Conditions

Frailty and sarcopenia in older people Signs and Symptoms

Shaun Hiu, Nina Wilson, Kevin Wilson, Nan Lin, Miles D. Witham et al. (7 authors)

Trials2026-04-09

Metformin and physical performance in older people with probable sarcopenia and physical prefrailty or frailty in England (MET-PREVENT): a double-blind, randomised, placebo-controlled trial.

Witham MD, McDonald C, Wilson N, Rennie KJ, Bardgett M, Bradley P, Clegg AP, Connolly S, Hancock H, Hiu S, Nicholson K, Robertson L, Simms L, Steel AJ, Steves CJ, Storey B, Wason J, von Zglinicki T, Sayer AA.

2025-03-247 citations

10.1016/j.lanhl.2025.100695

MET-PREVENT: metformin to improve physical performance in older people with sarcopenia and physical prefrailty/frailty – protocol for a double-blind, randomised controlled proof-of-concept trial

Katherine Rennie, Miles D. Witham, Penny Bradley, Andrew Clegg, Stephen Connolly et al. (18 authors)

BMJ Open2022-07-0115 citations

10.1136/bmjopen-2022-061823

Interventions

Participants will be randomised 1:1 into the metformin or placebo arms using a web-based randomisation system. They will receive metformin hydrochloride 500 mg or matching placebo three times a day fo

Eligibility

Sex/Gender

All

Age

65 Years to 100 Years

Inclusion criteria

Inclusion criteria: 1. Aged 65 years or over 2. Low maximum handgrip strength (<16 kg for women, <27 kg for men) 3. Walk speed <0.8 m/s on 4-m walk test

Exclusion criteria

Exclusion criteria: 1. Diabetes mellitus (type 1 or type 2) 2. eGFR 48 h of Bristol stool chart grade 6 or 7 ) 4. Alcohol intake >21 units/week (women) or >35 units/week (men) 5. Symptomatic chronic heart failure, diagnosed according to European Society of Cardiology guidelines (asymptomatic left ventricular systolic dysfunction will not be an exclusion criterion) 6. Liver function tests (bilirubin, alanine aminotransferase or alkaline phosphatase) >3x upper limit of normal 7. Oral steroid dose >7.5 mg prednisolone equivalent per day 8. Unable to mobilise without human assistance 9. Life expectancy of <3 months as adjudicated by the local investigator 10. Unable to give written informed consent 11. Previous intolerance of metformin or taking metformin for another condition 12. Currently participating in, or participated within 30 days, another intervention study (observational studies and registries are permitted)

Design outcomes

Primary

Measure	Time frame
4-m walk speed at 4 months	—

Secondary

Measure	Time frame
1. Fried frailty score, including individual components: 1.1. Activity level assessed using self-report questionnaire at baseline and 4 months 1.2. Exhaustion assessed using self-report questionnaire at baseline and 4 months 1.3. Grip strength assessed using Jamar handgrip dynamometer at baseline and 4 months 1.4. 4-m walk speed assessed using timed walk test over 4 m at baseline and 4 months 1.5. Weight assessed using calibrated scales at baseline and 4 months 2. Transitions from pre-frail to frail, death, inability to continue in trial, or to non-frail from baseline to 4 months 3. Lower limb muscle power measured using Short Physical Performance Battery at baseline and 4 months 4. 6-min walk distance assessed at baseline and 4 months 5. Total body muscle mass measured using bioimpedance at baseline and 4 months 6. Ability to perform activities of daily living assessed using the Nottingham Extended Activities of Daily Living Scale (EADL) at baseline and 4 months 7. Health related quality of life assessed using the EQ5D and SF-36 scales at baseline and 4 months 8. Trial metrics: 8.1. Conversion from screening to randomisation assessed using study records at screening and baseline study visits 8.2. Recruitment rate assessed using study records over the 10-month recruitment period 8.3. Retention rate assessed using study records over the 4-month participation period	—

Measure

Time frame

1. Fried frailty score, including individual components: 1.1. Activity level assessed using self-report questionnaire at baseline and 4 months 1.2. Exhaustion assessed using self-report questionnaire at baseline and 4 months 1.3. Grip strength assessed using Jamar handgrip dynamometer at baseline and 4 months 1.4. 4-m walk speed assessed using timed walk test over 4 m at baseline and 4 months 1.5. Weight assessed using calibrated scales at baseline and 4 months 2. Transitions from pre-frail to frail, death, inability to continue in trial, or to non-frail from baseline to 4 months 3. Lower limb muscle power measured using Short Physical Performance Battery at baseline and 4 months 4. 6-min walk distance assessed at baseline and 4 months 5. Total body muscle mass measured using bioimpedance at baseline and 4 months 6. Ability to perform activities of daily living assessed using the Nottingham Extended Activities of Daily Living Scale (EADL) at baseline and 4 months 7. Health related quality of life assessed using the EQ5D and SF-36 scales at baseline and 4 months 8. Trial metrics: 8.1. Conversion from screening to randomisation assessed using study records at screening and baseline study visits 8.2. Recruitment rate assessed using study records over the 10-month recruitment period 8.3. Retention rate assessed using study records over the 4-month participation period

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Countries

England, United Kingdom

Contacts

Public ContactMiles Witham

Miles.Witham@newcastle.ac.uk+44 (0)1912081317

Outcome results

None listed