Can metformin help with osteoarthritis (degenerative joint disease) of the knee?

Metformin for Knee Osteoarthritis

Metformin is strongly recommended against for the treatment of knee osteoarthritis as it has not demonstrated efficacy in established clinical guidelines, despite some promising recent research. 1

Current Guideline Recommendations

The 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis explicitly states that metformin is "strongly recommended against in patients with knee, hip, and/or hand OA" 1. This represents the most authoritative clinical guidance on the topic.

The EULAR (European League Against Rheumatism) recommendations also do not include metformin in their treatment algorithm for knee osteoarthritis, instead focusing on established treatments such as:

• Paracetamol as first-line oral analgesic
• NSAIDs (oral or topical)
• Intra-articular steroids
• Non-pharmacological interventions 1

First-Line Treatments for Knee Osteoarthritis

The evidence-based approach to knee osteoarthritis management includes:

1. Non-pharmacological interventions:

   • Exercise therapy (particularly quadriceps strengthening)
   • Weight reduction for overweight patients
   • Physical therapy
   • Appropriate use of assistive devices 2

2. Pharmacological treatments:

   • Topical NSAIDs as first-line pharmacotherapy
   • Acetaminophen/paracetamol for mild to moderate pain
   • Oral NSAIDs at lowest effective dose for shortest duration
   • Intra-articular corticosteroid injections for flares 2

Emerging Research on Metformin

Despite the strong recommendation against metformin in current guidelines, recent research has shown potential benefits:

• A 2025 randomized clinical trial demonstrated that metformin (2000 mg/day) reduced knee pain in patients with overweight or obesity and knee osteoarthritis compared to placebo, with a between-group difference of -11.4 mm on a 100-mm VAS pain scale (95% CI, -20.1 to -2.6 mm) 3

• Preclinical studies suggest metformin may have protective effects on cartilage through:

  • Anti-inflammatory properties
  • Regulation of AMPK/mTOR signaling pathways
  • Reduction of cartilage degradation 4, 5

• A retrospective study found that metformin use was associated with reduced risk of total knee arthroplasty and lower severity of knee pain in patients with knee OA and diabetes and/or obesity 6

• A clinical trial protocol has been registered to examine the effects of metformin on knee cartilage volume loss and symptoms in overweight knee OA patients over 24 months 7

Clinical Decision Making

Despite these promising research findings, the current clinical guidelines take precedence in medical decision-making. The 2019 ACR/AF guideline's strong recommendation against metformin for knee OA reflects the consensus of expert opinion based on available evidence at that time.

Conclusion for Clinical Practice

While emerging research shows potential benefits of metformin for knee osteoarthritis, particularly in patients with overweight or obesity, current authoritative guidelines strongly recommend against its use for this indication. Clinicians should follow established treatment algorithms focusing on proven interventions such as exercise therapy, weight management, appropriate analgesics, and intra-articular treatments until larger confirmatory trials lead to changes in clinical guidelines.

For patients interested in metformin for knee OA, consider referring them to clinical trials investigating this treatment approach rather than prescribing off-label.