Metformin Does Not Cause Joint Pain—It May Actually Reduce It
No, an increased dose of metformin does not cause joint pain in diabetic patients. In fact, emerging evidence suggests metformin may have protective effects against musculoskeletal pain, including joint pain.
Known Side Effects of Metformin
The established adverse effects of metformin are well-documented in major diabetes guidelines and do not include joint pain:
- Gastrointestinal effects are the principal side effects, including bloating, abdominal discomfort, and diarrhea 1, 2
- Vitamin B12 deficiency can occur with long-term use, potentially worsening peripheral neuropathy symptoms 1, 2, 3
- Lactic acidosis is a rare but serious complication, typically occurring only with severe renal impairment (eGFR <30 mL/min/1.73 m²), overdose, or acute illness 3
- Reduced appetite may be problematic in some patients, particularly older adults 2, 3
Joint pain is notably absent from the comprehensive list of metformin's recognized adverse effects across all major diabetes guidelines 1, 2, 3, 4.
Evidence Suggesting Protective Effects Against Joint Pain
Recent high-quality research indicates metformin may actually reduce musculoskeletal pain:
A large cross-sectional study of 21,889 UK Biobank participants with type 2 diabetes found that those taking metformin had significantly lower odds of musculoskeletal pain in the back (chronic pain OR 0.87,95% CI 0.81-0.93), knee (chronic pain OR 0.87,95% CI 0.81-0.94), and neck/shoulder regions (chronic pain OR 0.92,95% CI 0.85-0.99) compared to those not taking metformin 5
A 2025 randomized controlled trial published in JAMA demonstrated that metformin significantly reduced knee pain in patients with knee osteoarthritis and overweight/obesity, with a between-group difference of -11.4 mm on a 100-mm visual analog scale (95% CI -20.1 to -2.6 mm; P = .01) at 6 months 6
Metformin appears to have analgesic and neuroprotective properties through multiple mechanisms, including activation of adenosine monophosphate-activated protein kinase, reduction of neuroinflammation, and clearance of methylglyoxal 7
Animal studies show metformin protects articular cartilage from damage secondary to type 2 diabetes and reduces inflammatory hyperalgesia 8, 9
Clinical Implications
If a diabetic patient on metformin develops joint pain, clinicians should look for alternative explanations rather than attributing it to metformin:
- Consider diabetic complications such as Charcot arthropathy or diabetic muscle infarction
- Evaluate for concurrent osteoarthritis, which is more prevalent in diabetic patients
- Assess for vitamin B12 deficiency-related neuropathy if the patient has been on long-term metformin 1, 2
- Rule out other medication side effects or unrelated musculoskeletal conditions
The gastrointestinal side effects that may occur with dose escalation can be minimized by starting at 500 mg once or twice daily with food and titrating gradually to the maximum effective dose of 2000 mg/day 1, 2.