Objective Osteoarthritis (OA) is a frequent comorbidity in patients with type 2 diabetes mellitus (T2DM), significantly affecting health status and quality of life. Emerging evidence suggests metformin, a first-line agent for T2DM, may also have therapeutic effects on OA. This study aimed to evaluate the efficacy of metformin in improving symptoms and reducing the risk of joint replacement in patients with both OA and T2DM through a systematic review and meta-analysis. Methods A comprehensive search was conducted across PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure (CNKI) for studies published up to June 2025. Eligible studies included randomized controlled trials, cohort studies, and retrospective analyses examining metformin use in patients with OA and T2DM. Data on clinical outcomes—including the Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), total knee replacement (TKR), and total hip replacement (THR)—were extracted. Pooled effect sizes were calculated using random-effects models. Subgroup analyses were performed based on study design, metformin dosage, and treatment duration. Results Ten studies involving 243,221 participants were included. Metformin use significantly lowered TKR risk (HR = 0.46; 95% CI: 0.30–0.72) and improved pain scores (SMD = -2.04; 95% CI: -2.44 to -1.64). Subgroup analyses revealed that higher daily dosages (≥ 1.0 g/d) and longer treatment durations (≥ 24 months) were associated with greater reductions in joint replacement risk (HR = -0.95 and HR = -1.53, respectively). For symptomatic relief, randomized controlled trials (RCTs) consistently showed significant improvements across VAS pain (SMD = -1.90), WOMAC pain (SMD = -2.16), and functional scores (SMD = -1.49). Dose-escalation regimens (500–2000 mg/d) and 12-week interventions generally yielded the most pronounced improvements in pain and stiffness. The pooled odds ratio for non-serious adverse events was 2.07 (95% CI: 1.19–3.60), indicating a higher frequency of mild side effects such as gastrointestinal distress; however, no serious metformin-related events were reported. Conclusion Metformin use in patients with T2DM and OA is associated with significant reductions in pain and a decreased risk of TKR. Subgroup findings suggest that the benefits are dose- and duration-dependent, with RCT evidence strongly supporting symptomatic improvement. Further high-quality trials are warranted to define optimal dosing regimens.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> Key Points • Metformin therapy significantly alleviates joint pain and stiffness in patients with comorbid type 2 diabetes and osteoarthritis. • Metformin is associated with improved physical function, with randomized controlled trials showing consistent functional benefits. • Metformin use is associated with a significantly reduced risk of total knee replacement (TKR), while no statistically significant association is observed for total hip replacement (THR). • The protective association with joint replacement appears dose- and duration-dependent, with daily doses ≥ 1.0 g and treatment durations ≥ 24 months showing the greatest benefit. </entry> </row> </tbody> </tgroup> </Table>

Effectiveness of metformin in the management of osteoarthritis in patients with type 2 diabetes

期刊论文
发表日期：

2026年2月6日

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Ziyuan Chen,
Ling Jin,
Qian Lin,
Pengfei Liu,
Neng Li,
Xike Liu

摘要

Objective

Osteoarthritis (OA) is a frequent comorbidity in patients with type 2 diabetes mellitus (T2DM), significantly affecting health status and quality of life. Emerging evidence suggests metformin, a first-line agent for T2DM, may also have therapeutic effects on OA. This study aimed to evaluate the efficacy of metformin in improving symptoms and reducing the risk of joint replacement in patients with both OA and T2DM through a systematic review and meta-analysis.

Methods

A comprehensive search was conducted across PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure (CNKI) for studies published up to June 2025. Eligible studies included randomized controlled trials, cohort studies, and retrospective analyses examining metformin use in patients with OA and T2DM. Data on clinical outcomes—including the Visual Analogue Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), total knee replacement (TKR), and total hip replacement (THR)—were extracted. Pooled effect sizes were calculated using random-effects models. Subgroup analyses were performed based on study design, metformin dosage, and treatment duration.

Results

Ten studies involving 243,221 participants were included. Metformin use significantly lowered TKR risk (HR = 0.46; 95% CI: 0.30–0.72) and improved pain scores (SMD = -2.04; 95% CI: -2.44 to -1.64). Subgroup analyses revealed that higher daily dosages (≥ 1.0 g/d) and longer treatment durations (≥ 24 months) were associated with greater reductions in joint replacement risk (HR = -0.95 and HR = -1.53, respectively). For symptomatic relief, randomized controlled trials (RCTs) consistently showed significant improvements across VAS pain (SMD = -1.90), WOMAC pain (SMD = -2.16), and functional scores (SMD = -1.49). Dose-escalation regimens (500–2000 mg/d) and 12-week interventions generally yielded the most pronounced improvements in pain and stiffness. The pooled odds ratio for non-serious adverse events was 2.07 (95% CI: 1.19–3.60), indicating a higher frequency of mild side effects such as gastrointestinal distress; however, no serious metformin-related events were reported.

Conclusion

Metformin use in patients with T2DM and OA is associated with significant reductions in pain and a decreased risk of TKR. Subgroup findings suggest that the benefits are dose- and duration-dependent, with RCT evidence strongly supporting symptomatic improvement. Further high-quality trials are warranted to define optimal dosing regimens.

Key Points

• Metformin therapy significantly alleviates joint pain and stiffness in patients with comorbid type 2 diabetes and osteoarthritis.

• Metformin is associated with improved physical function, with randomized controlled trials showing consistent functional benefits.

• Metformin use is associated with a significantly reduced risk of total knee replacement (TKR), while no statistically significant association is observed for total hip replacement (THR).

• The protective association with joint replacement appears dose- and duration-dependent, with daily doses ≥ 1.0 g and treatment durations ≥ 24 months showing the greatest benefit.