Anti-Diabetic Drug, Exercise and Healthy Diet for Knee Osteoarthritis With Overweight/Obesity

NCT07065591 | Not Yet Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: UW25-051
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief Summary

Obesity is associated with increased pain with knee osteoarthritis and increase progression of knee osteoarthritis while weight loss intervention has been shown to reduce pain and requirement of total knee replacement. In this study, the investigators will assess using diet modification with exercise, and metformin, a common, safe, diabetes mellitus medication that has been in use for 70 years to achieve better weight control to reduce knee pain. This helps the investigators to understand whether the combined treatment can reduce joint pain, reduce body weight and improve symptoms and requirement of total knee replacement.

Conditions

Osteoarthritis (OA) of the Knee

Keywords

knee osteoarthritis; diet modification; exercise therapy

Outcome Measures

Primary Outcomes (1)

• Pain by visual analogue scale

  Measure the change in pain level through visual analogue scale (VAS) (0-100mm)

  At 0,1.5, 3, 6 and 12 months

Secondary Outcomes (24)

• Western Ontario and McMaster Universities Arthritis Index (WOMAC)

  At 0,1.5, 3, 6 and 12 months

• Body weight

  At 0,1.5, 3, 6 and 12 months

• Knee stiffness

  At 0,1.5, 3, 6 and 12 months

• Physical Activity through questionnaire

  At 0,1.5, 3, 6 and 12 months

• Willingness to proceed TKR immediately

  At 0,1.5, 3, 6 and 12 months

Study Arms (2)

Intervention group

EXPERIMENTAL

This group of patients will receive metformin (max: 500mgx4=2000mg daily). Both groups will start with an initial dose of 500mg daily and the dose will be gradually titrated to 2000mg daily in 6 weeks to allow patients adopting to the gastrointestinal symptoms. Both groups shall be put on metformin or placebo for 6months and then both groups will stop their respective medications and continue on diet modification and exercise therapy only.

Drug: Metformin

Placebo

PLACEBO COMPARATOR

This group of patients will receive placebo. The placebos will be manufactured with Good Manufacturing Practice (GMP) standard such that each placebo pill will look like metformin pill (500mg). Both groups will start with an initial dose of 500mg daily and the dose will be gradually titrated to 2000mg daily in 6 weeks to allow patients adopting to the gastrointestinal symptoms. Both groups shall be put on metformin or placebo for 6months and then both groups will stop their respective medications and continue on diet modification and exercise therapy only.

Other: Placebo

Interventions

Metformin DRUG

The intervention group will receive metformin (max: 500mgx4=2000mg daily). Both groups will start with an initial dose of 500mg daily and the dose will be gradually titrated to 2000mg daily in 6 weeks to allow patients adopting to the gastrointestinal symptoms. Both groups shall be put on metformin or placebo for 6months and then both groups will stop their respective medications and continue on diet modification and exercise therapy only.

Also known as: Metfomin

Intervention group

Placebo OTHER

The placebo group will receive placebo. The placebos will be manufactured with Good Manufacturing Practice (GMP) standard such that each placebo pill will look like metformin pill (500mg). Both groups will start with an initial dose of 500mg daily and the dose will be gradually titrated to 2000mg daily in 6 weeks to allow patients adopting to the gastrointestinal symptoms. Both groups shall be put on metformin or placebo for 6months and then both groups will stop their respective medications and continue on diet modification and exercise therapy only.

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women age between 40 and 80 years old, with overweight or obesity (body mass index ≥23 kg/m2) according to Hong Kong Centre for Health Protection definition of overweight and obesity.
• Knee pain for 6+ months with Visual Analogue Scale (VAS) \> 40mm/100mm and
• Meet the American College of Rheumatology criteria for knee OA
• OA referred for consideration for joint replacement

You may not qualify if:

• Severe radiographic knee OA (Kellgren-Lawrence grade 4) or severe knee pain (VAS\>80mm/100 mm) that could not tolerate further conservative management;
• inflammatory arthritis like rheumatoid arthritis, crystal arthritis, etc.
• Preexisting diabetes on antidiabetic drug or drug allergy to metformin.
• Recent knee surgery of the same knee
• Significant bone loss.
• Concomitant neuromuscular diseases affecting lower limb function.
• renal or liver impairment precluding use of metformin.
• VitaminB12 deficiency

Sponsors & Collaborators

• The University of Hong Kong: lead

MeSH Terms

Conditions

Osteoarthritis; Osteoarthritis, Knee

Interventions

Metformin

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Central Study Contacts

Lawrence Lau, FRCS, PhD

CONTACT

+852 92646862; laucml@hku.hk

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: June 29, 2025
• First Posted: July 15, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): April 17, 2028
• Study Completion (Estimated): July 17, 2028
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share