The AMPK Modulator Metformin as a Novel Adjunct to Conventional Therapy in Patients With Knee Osteoarthritis

The AMPK Modulator Metformin as a Novel Adjunct to Conventional Therapy in Patients With Knee Osteoarthritis: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

metformin alleviates drug-induced osteoarthritis (OA)-like change in mice knee joint through activating autophagy and downregulating apoptosis. Metformin exerts its protective effects against OA through the AMPKa2/ SIRT1 pathway. Metformin suppresses IL-1β-induced oxidative and osteoarthritis-like inflammatory changes by enhancing the SIRT3/PINK1/Parkin signaling pathway, thereby indicating metformin's potential in prevention and treatment of osteoarthritic joint disease.

Inclusion Criteria:

• Primary osteoarthritis Patients recruited were between 30 to 60 years of age, with X-ray confirmed Kellgren-Lawrence grade13 II or III severity primary tibiofemoral OA, according to the American College of Rheumatology criteria.

Exclusion Criteria:

Those patients were excluded from the present study who:

• were of age less than 30 years or more than 60 years
• presented with active concomitant gastroduodenal disorders, hepatic and renal impairment within last 30 days prior to receiving the study drug
• were diagnosed to have any inflammatory arthritis, gout or acute trauma of the knee, hip or spine; accompanying OA of the hip of sufficient severity to interfere with the functional assessment of the knee
• had previous or ongoing treatment with oral SYSDOA (e.g., glucosamine sulphate, chondroitin sulphate, diacerein, piascledine), anti-depressants, tranquillisers, antacids or antibiotics; were having active cardiac lesion or hypertension, were pregnant females and those who were planning their pregnancy during the study
• were having a known hypersensitivity to the used medications
• have persistent diarrhoea or laxative use; severe gastrointestinal disorders, severe obesity, severe parenchymal organ disease, or anaemia (haemoglobin< 10.0 g/ dl or haematocrit < 30%).
• Patients who received oral, intramuscular, intraarticular or soft tissue injections of corticosteroids within last eight weeks before receiving the first dose of the study medication, or had undergone joint lavage and arthroscopic procedures in the previous 6 months, were also excluded.