Metformin Treatment of Patients with Hand Osteoarthritis

Inclusion criteria

• Age ≥18 years
• Hand OA according to the ACR criteria
• Average finger (2 to 5) pain ≥4 on a 0-10 numeric rating scale (NRS where 10 is worst pain) over the past 30 days
• Metformin naive

Exclusion criteria

Comorbidities

• History of, or current signs of medical disease that may affect joints, e.g. rheumatoid arthritis, gout, psoriatic arthritis
• Psoriasis
• Known malignancy (except successfully treated squamous or basal cell skin carcinoma)
• Drug or alcohol abuse in the last year
• Existing nerve entrapment syndromes (e.g. carpal tunnel syndrome)
• Known diabetes
• Generalised pain syndromes such as fibromyalgia
• Known peripheral neuropathies
• Known allergies towards the interventions
• Gastric bypass or other malabsorption syndrome
• In case of pharmacological weight loss medication (e.g. glucagon like peptide-1 (GLP-1) analogues) or pharmacological osteoporosis medication, dosage must have been stable for 3 months without any plan of up-titration during the study period
• Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or obstructs participation e.g. psychiatric disorders.

Surgical history

• History of hand surgery in the target hand within 12 months prior to enrolment
• History of arthroplasty, arthrodesis or surgical treatment of thumb base osteoarthritis in the target hand

Management strategies

• Use of systemic corticosteroids equivalent of ≥ 7.5 mg prednisolone daily within 3 months
• Treatment with denosumab (Prolia/Xgeva)
• Participation in experimental device or experimental drug study 3 months prior to enrolment
• Intra-articular treatments of any kind of any joint of the target hand 3 months before inclusion
• Current use of synthetic or non-synthetic opioids
• Planning to start other treatment for hand OA in the study participation period
• Planned CT scan with iodine contrast
• Scheduled surgery on upper extremity of the target hand during study participation
• Scheduled surgery requiring pause of metformin, e.g. surgery in general anaesthesia, during study participation

Reproductive system

• Pregnancy
• Planned pregnancy within the study period, 3 months after end of study treatment for female fertile participant and 6 months after end of study treatment for male participant
• Insufficient anti-conception therapy for female fertile participants within the study period and 3 months after end of study treatment

• Sufficient anti-conception therapy consists of intra-uterine device (coil), hormonal anti-conception (birth control pills, implant, intra-uterine system, dermal patch, vaginal ring, or injections) or sexual abstinence
• Female participants are considered infertile if they are postmenopausal or if they have undergone surgical sterilisation (bilateral salpingectomy, hysterectomy or bilateral oophorectomy)
• Postmenopausal state is defined as no menses for 12 months without alternative medical cause before inclusion in the study
• Insufficient anti-conception therapy for male participants within the study period and 6 months after end of study treatment

• Sufficient anti-conception therapy consists of condom or sexual abstinence
• Male participants are considered sterile if they have undergone surgical sterilisation (vasectomy)
• Breast-feeding

Blood analysis

• Positive anti-cyclic citrullinated peptide (>10 kU/L)
• eGFR <60 ml/min/1.73 m2
• Vitamin B12 deficiency < 200 pmol/L
• Hba1c ≥ 48 mmol/mol