Inclusion/Exclusion Criteria

Inclusion:

To be eligible to enter the trial participants must fulfil all of the following:

1. Diagnosis of LFS from confirmed pathogenic TP53 variant (class IV or V by CanVIG-UK criteria (see appendix 2)
2. Aged ≥16 years
3. Capable of understanding the consent process and participating in the trial and according to the investigators’ discretion.

Exclusion:

1. Currently taking metformin
2. Metformin intake for more than 3 months in total, within the 2 years antecedent to the date of trial enrolment
3. Completion of cancer systemic therapy within the  6 months antecedent to the date of trial enrolment
4. Current type 1 or 2 diabetes mellitus
5. Presence of active ongoing cancer /or currently receiving cancer treatment (excluding maintenance treatments e.g., hormones)
6. Current pregnancy or lactation
7. Gastro-intestinal condition (such as short-bowel syndrome) that would affect absorption of metformin
8. Concurrent medical condition (other than LFS) that could result in life expectancy of <5 years
9. History of the following cardiac conditions:
1. Congestive cardiac failure of > Grade II severity according to the New York Heart Association Functional Classification (defined as symptomatic at less than ordinary levels of activity).
2. Ischaemic cardiac event including myocardial infarction within 3 months prior to date of enrolment.
3. Uncontrolled cardiac disease, including unstable angina pectoris, uncontrolled hypertension (i.e., sustained systolic BP > 160 mmHg or diastolic BP > 90 mm Hg)
10. Evidence of significant renal impairment eGFR < 50ml/minute/1.73m2
11. Liver cirrhosis and/or alkaline phosphatase, aspartate transaminase or alanine transaminase >2.5 x upper limit of normal (ULN)
12. Elevated risk of lactic acidosis such as current chronic alcoholism, congenital lactic acidosis, concurrent intake of carbonic anhydrase inhibitor (e.g. acetazolamide)
13. Known allergy to metformin
14. Does not fulfil MRI Safety Screening criteria (e.g. implanted cardiac pacemaker, post-surgical metal hardware – plates etc) and/or unable to undergo baseline scan.