Anti-diabetic Medication Combined With Exercise and Healthy Diet Treatment

Government-funded | Free* support services | First come, first served | Recruiting 100 participants

Anti-diabetic Medication Combined With Exercise and Healthy Diet Treatment

Support Programme for Overweight Knee Osteoarthritis Patients

Eligible participants may receive free* follow-up from an orthopaedic specialist, dietitian and physiotherapist. Programme medication, either metformin or placebo, will be arranged under doctor assessment and safety monitoring. Places are processed according to preliminary application and eligibility verification order.

* Programme medication is provided free of charge by the programme. If hospital registration is required for medication collection, the usual hospital registration fee still applies.

This programme is jointly run by The University of Hong Kong and Queen Mary Hospital, with government funding. It is designed for people with knee osteoarthritis and higher body weight, combining specialist clinical follow-up, diet and exercise support, and doctor-monitored adjunct medication to support knee pain, function, weight management and metabolic health.

Start Application View Programme Details

Programme Overview

For people with knee pain, higher body weight and a need for orthopaedic assessment

The programme provides structured follow-up by an orthopaedic specialist, dietitian and physiotherapist, together with adjunct medication under medical assessment and safety monitoring. The aim is to support participants through coordinated management of knee symptoms, body weight, physical function and metabolic health.

Participants will follow a planned assessment and follow-up schedule. Items may include knee pain and daily function questionnaires, physical function tests, body weight and muscle assessment, blood tests and knee X-rays. Existing orthopaedic care will continue to be handled according to clinical need.

Government-funded and free* support Eligible participants may receive free* follow-up from an orthopaedic specialist, dietitian and physiotherapist. Programme medication, metformin or placebo, is provided free of charge and arranged under doctor assessment and safety monitoring.
Recruitment places The programme plans to recruit 100 participants. Places are handled on a first-come, first-served basis after preliminary application and eligibility checking.
Ethics approval This programme has received medical ethics approval. Reference number: HKWC-2024-309.
Who may be suitable People aged over 40, BMI >= 23, knee pain for at least 6 months, with confirmed or suspected knee osteoarthritis requiring orthopaedic assessment, and with no diabetes or diabetes not currently treated with diabetes medication.
Enquiry For programme enquiries, please call 9793 8590.

Programme Components

Three core follow-up services + adjunct medication treatment

The programme integrates orthopaedic, nutrition and physiotherapy follow-up with doctor-monitored adjunct medication. These components work together to address joint symptoms, weight-related knee loading, muscle function and metabolic risk.

Orthopaedic specialist follow-up An orthopaedic specialist will assess knee condition, pain severity, X-ray findings and overall health risks, and monitor knee pain, stiffness, function and safety indicators during follow-up.
Dietitian follow-up A dietitian will provide practical dietary guidance based on eating habits, weight goals and daily routine, supporting weight management and metabolic indicators such as blood glucose and lipids.
Physiotherapist follow-up A physiotherapist will guide knee osteoarthritis-appropriate exercises and home training to improve lower limb strength, walking ability, balance and day-to-day function.
Adjunct medication treatment Metformin-related arrangements, where applicable, will be made under doctor assessment and safety monitoring. Published evidence links metformin with reduced knee pain, slower knee osteoarthritis progression, metabolic health support and diabetes prevention.

Metformin Information

Evidence for knee osteoarthritis and metabolic health

Metformin is a well-established medication used clinically for many years.[6] Clinical trials, systematic reviews and basic science studies report evidence relating to knee osteoarthritis pain, stiffness, physical function, quality of life, inflammation, cartilage degeneration and subchondral bone changes.[1-5,8,9] Suitability still requires doctor assessment based on individual health status and safety indicators.[1,6]

The 2026 OrthoEvidence ACE Report and the related systematic review and meta-analysis summarised 5 randomised controlled trials involving 337 patients with knee osteoarthritis. Their pooled results favoured metformin over control for pain, stiffness, physical function and quality of life at final follow-up.[8,9]

Reduced knee pain A 2025 JAMA randomised clinical trial in people with overweight or obesity and knee osteoarthritis found greater reduction in knee pain VAS score after 6 months with metformin than placebo.[1]
Slower osteoarthritis progression Animal model work in Annals of the Rheumatic Diseases reported that metformin limited osteoarthritis development and progression through AMPK signalling, and improved pain-related behaviour.[2]
Reduced osteophyte formation and cartilage damage Mouse model evidence reported reductions in DMM-induced osteophyte formation, articular cartilage damage and chondrocyte pyroptosis, with improvement in subchondral bone remodelling.[3]
Improved subchondral osteosclerosis Journal of Orthopaedic Surgery and Research reported that metformin alleviated osteoarthritis in mice by inhibiting chondrocyte ferroptosis and improving subchondral osteosclerosis and abnormal angiogenesis.[4]
Improved inflammatory and cartilage markers A 2024 clinical trial in obese knee osteoarthritis patients reported improved WOMAC scores and lower COMP, CTX-1 and IL-1 beta with metformin as adjunct therapy.[5]
Diabetes prevention The Diabetes Prevention Program showed that metformin reduced progression to type 2 diabetes in high-risk adults, especially relevant to people with higher body weight and metabolic risk.[6]
Healthy ageing direction Metformin has been discussed internationally as a tool to target ageing-related pathways including AMPK, insulin signalling and inflammation. This is a healthy ageing direction, not a guarantee of longer lifespan for an individual.[7]

ACE Report Graph Summary

Pooled analysis favoured metformin across several symptom outcomes

The graph below redraws final follow-up results from the OrthoEvidence ACE Report. A standardised mean difference further left favours metformin.

5Randomised controlled trials
337Knee osteoarthritis patients
4-24 weeksFollow-up range
Symptom gainsPain, stiffness, function and quality of life
Favours metforminNo differenceFavours control
Pain
SMD -1.30 (-2.06 to -0.53)
Stiffness
SMD -0.75 (-1.38 to -0.11)
Physical function
SMD -2.04 (-3.37 to -0.71)
Quality of life
SMD -1.50 (-2.90 to -0.12)

Graph redrawn from the OrthoEvidence ACE Report and Kao et al.; this is not a screenshot from the original report.[8,9] The ACE Report rated overall certainty as critically low, so all medication-related arrangements still require individual doctor assessment.

Who May Join

Preliminary eligibility

Online application is for preliminary contact and information collection only. Final suitability will be confirmed by the team based on medical history, X-ray, blood tests and clinical assessment.

May be suitable
  • Age over 40 years.
  • BMI >= 23 kg/m2.
  • Knee pain for at least 6 months, usually with pain severity above 40/100.
  • Confirmed or suspected knee osteoarthritis and currently receiving or requiring orthopaedic assessment.
  • No diabetes, or diabetes but not currently taking diabetes medication.
  • Able to attend follow-up around 1.5, 3, 6 and 12 months.
May not be suitable
  • Knee condition requiring immediate or other specialised clinical management.
  • Inflammatory arthritis, such as rheumatoid arthritis or crystal arthritis.
  • Diabetes currently treated with glucose-lowering medication, or previous sensitivity to metformin.
  • Recent surgery on the same knee, major bone defect, or neurological or muscular problems affecting lower limb function.
  • Liver or kidney function unsuitable for metformin, or vitamin B12 deficiency.

Follow-up Timeline

Expected participant pathway

The schedule below summarises the main participant-facing arrangements. Actual timing and content will be confirmed according to doctor assessment, test results and individual circumstances.

After application: preliminary contact and eligibility checking The team will check the online form information, including age, BMI, knee pain duration, knee osteoarthritis status, diabetes and medication status, liver and kidney related information, and contact details.
Month 0: hospital assessment and start of follow-up An orthopaedic specialist appointment will be arranged at 7/F, Block S, Queen Mary Hospital. Baseline questionnaires, physical function tests, body and muscle assessment, blood tests, dietitian follow-up and physiotherapy exercise guidance may also be arranged.
Weeks 1 to 6: establishing treatment and lifestyle routine If metformin-related arrangements apply, dosing will start low and be adjusted under doctor monitoring. Participants will begin diet, weight management and home exercise plans.
1.5 and 3 months: short-term follow-up The team will review knee pain, daily function, activity and quality of life, with brief physical function and weight-related assessments. Orthopaedic, dietitian and physiotherapy follow-up will be adjusted as needed.
6 months: mid-programme assessment A more complete review may include questionnaires, physical function tests, body and muscle assessment, blood tests and knee X-ray. The team will review symptoms, metabolic indicators and safety items.
6 to 12 months: maintenance follow-up Adjunct medication treatment is usually concentrated in the first 6 months. Follow-up then continues for symptoms, weight, activity function and safety, with relevant dietitian and physiotherapist input.
12 months: main follow-up assessment The main follow-up is completed with questionnaires, physical function tests, body and muscle assessment, blood tests and knee X-ray to understand changes over one year.

Participant Documents

Browse participant documents

Please read the relevant documents first. This online form is for preliminary contact and arrangement only, and does not replace the formal consent process.

English Participant Information / ICF PDF, Version 1.0, 10 Dec 2024 Chinese Participant Information / ICF PDF, Version 3.0, 27 Mar 2025

Application

Preliminary application form

After submission, the system will show an application number. The programme team will verify whether your health information meets the preliminary criteria. If eligible, we will contact you. For enquiries, please call 9793 8590.

Preliminary Health Information
Contact Details
Signature Confirmation

I confirm that the above information is provided by me, and I agree that the programme team may use the above information for preliminary contact and arrangement.

References

References

The references below are provided as background information. Actual arrangements depend on doctor assessment, programme procedures and individual health status.

  1. Pan F, Wang Y, Lim YZ, et al. Metformin for Knee Osteoarthritis in Patients With Overweight or Obesity: A Randomized Clinical Trial. JAMA. 2025;333(20):1804-1812. PubMed
  2. Li J, Zhang B, Liu WX, et al. Metformin limits osteoarthritis development and progression through activation of AMPK signalling. Annals of the Rheumatic Diseases. 2020;79(5):635-645. PubMed
  3. Yan J, Ding D, Feng G, et al. Metformin reduces chondrocyte pyroptosis in an osteoarthritis mouse model by inhibiting NLRP3 inflammasome activation. Experimental and Therapeutic Medicine. 2022;23(3):222. PubMed
  4. Yan J, Feng G, Ma L, Chen Z, Jin Q. Metformin alleviates osteoarthritis in mice by inhibiting chondrocyte ferroptosis and improving subchondral osteosclerosis and angiogenesis. Journal of Orthopaedic Surgery and Research. 2022;17(1):333. PubMed
  5. Aiad AAE, El-Haggar SM, El-Barbary AM, El-Afify DR. Metformin as adjuvant therapy in obese knee osteoarthritis patients. Inflammopharmacology. 2024;32(4):2349-2359. PubMed
  6. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin. New England Journal of Medicine. 2002;346(6):393-403. PubMed
  7. Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metabolism. 2016;23(6):1060-1065. PubMed
  8. OrthoEvidence. The efficacy of metformin for pain, function, and quality of life in knee osteoarthritis: A systematic review and meta-analysis. OE Journal - ACE Report. ACE Report
  9. Kao CL, Chen SM, Hsieh CC, Peng TR, Tsai PY, Lin CY, Lee MC. The efficacy of metformin for pain, function, and quality of life in knee osteoarthritis: A systematic review and meta-analysis. Seminars in Arthritis and Rheumatism. 2026. doi:10.1016/j.semarthrit.2025.152908. DOI