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.
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
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
Parallel
Metformin
DrugThe 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.
Placebo
Other interventionThe 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.
Pain by visual analogue scale
Measure the change in pain level through visual analogue scale (VAS) (0-100mm)
Western Ontario and McMaster Universities Arthritis Index (WOMAC)
Western Ontario and McMaster Universities Arthritis Index (WOMAC) consists of 24 items divided into 3 subscales Pain (5 items), Stiffness (2 items)Physical Function (17 items). The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. A sum of the scores for all three subscales gives a total WOMAC score.
Body weight
Body weight (kg - kilogram) will be measured at each visit.
Knee stiffness
It is measured by knee range measurement
Physical Activity through questionnaire
It is measured by the International Physical Activity Questionnaire short version. Results can be reported in categories (low activity levels, moderate activity levels or high activity levels) or as a continuous variable (MET minutes a week).
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