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

Abstract

Introduction Skeletal muscle dysfunction is central to both sarcopenia and physical frailty, which are associated with a wide range of adverse outcomes including falls and fractures, longer hospital stays, dependency and the need for care. Resistance training may prevent and treat sarcopenia and physical frailty, but not everyone can or wants to exercise. Finding alternatives is critical to alleviate the burden of adverse outcomes associated with sarcopenia and physical frailty. This trial will provide proof-of-concept evidence as to whether metformin can improve physical performance in older people with sarcopenia and physical prefrailty or frailty. Methods and analysis MET-PREVENT is a parallel group, double-blind, placebo-controlled proof-of-concept trial. Trial participants can participate from their own homes, including completing informed consent and screening assessments. Eligible participants with low grip strength or prolonged sit-to-stand time together with slow walk speed will be randomised to either oral metformin hydrochloride 500 mg tablets or matched placebo, taken three times a day for 4 months. The recruitment target is 80 participants from two secondary care hospitals in Newcastle and Gateshead, UK. Local primary care practices will act as participant identification centres. Randomisation will be performed using a web-based minimisation system with a random element, balancing on sex and baseline walk speed. Participants will be followed up for 4 months post-randomisation, with outcomes collected at baseline and 4 months. The primary outcome measure is the four metre walk speed at the 4-month follow-up visit. Ethics and dissemination The trial has been approved by the Liverpool NHS Research Ethics Committee (20/NW/0470), the Medicines and Healthcare Regulatory Authority (EudraCT 2020-004023-16) and the UK Health Research Authority (IRAS 275219). Results will be made available to participants, their families, patients with sarcopenia, the public, regional and national clinical teams, and the international scientific community. Trial registration number NCT29932357.

Clinical efficacy and cost‐effectiveness of metformin in different patient populations: A narrative review of real‐world evidence

“…66 It is hoped that a recently planned proof-of-concept study (MET-PREVENT) will provide evidence on whether metformin can improve physical performance in frail elderly subjects with sarcopenia. 67…”

“…RWE on the relationship between sarcopenia and metformin use is scarce but a cross‐sectional observation performed in a small cohort of Chinese elderly individuals with T2D showed that metformin, alone or in combination with other drugs, lowers the risk of sarcopenia 66 . It is hoped that a recently planned proof‐of‐concept study (MET‐PREVENT) will provide evidence on whether metformin can improve physical performance in frail elderly subjects with sarcopenia 67 …”

Repurposing Drugs for Diabetes Mellitus as Potential Pharmacological Treatments for Sarcopenia – A Narrative Review

“…A number of other trials are under way that seek to test the effects of metformin on skeletal muscle function. Of particular note are a randomised, placebo-controlled trial enrolling participants with impaired glucose tolerance [ 108 ], testing metformin up to 1 g twice daily versus placebo for 2 years, and a trial (MET-PREVENT) [ 109 ] enrolling older people with probable sarcopenia, testing metformin 500 mg three times a day versus placebo for 4 months. The results of these trials are necessary to test whether the potential advantages of metformin outweigh any adverse effects of metformin on appetite, food intake, weight and exercise benefits.…”

Therapie der physischen Frailty

“…Auch bereits in anderen Indikationen etablierte Substanzen werden hinsichtlich ihrer Wirksamkeit geprüft. So wird derzeit in einer randomisierten kontrollierten Studie untersucht, ob Metformin bei älteren Personen mit Sarkopenie und Pre-Frailty oder Frailty eine positive Wirkung auf die körperliche Leistungsfähigkeit ausübt [26].…”