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Objective <p>Intervertebral disc degeneration (IDD) is a major contributor to low back pain and disability. Emerging evidence suggests that type 2 diabetes mellitus (T2DM) accelerates IDD progression, while metformin, a first-line treatment for T2DM, may offer protective effects. This study aimed to evaluate the association between metformin use and long-term IDD risk in T2DM patients using data from the UK Biobank.</p> Methods <p>A prospective cohort of 20,350 individuals with T2DM was analyzed, including 11,158 metformin users and 9192 non-users. The primary outcome was incident IDD, identified via ICD-10 codes. Cox proportional hazards models estimated hazard ratios (HRs) for IDD, adjusting for demographic, behavioral, and clinical factors. A sensitivity analysis was performed by excluding patients with a follow-up period of less than 2 years to assess the stability of the results. Subgroup and interaction analyses explored effect modifiers. Predictive models using Cox regression were developed to estimate 5- and 13-year IDD risk, with model performance evaluated by area under the ROC curve (AUC).</p> Results <p>Over a median follow-up of 13 years, metformin use was significantly associated with a reduced risk of IDD [HR (95% CI): 0.863 (0.753–0.989), <i>p</i> = 0.034]. The results were robust in the sensitivity analysis[HR (95% CI): 0.862 (0.749–0.992), <i>p</i> = 0.039]. A significant interaction with sleep time and hypertension status were observed (P for interaction &lt; 0.05). Predictive model AUCs for 5- and 13-year IDD risk were 0.64 (95% CI: 0.57–0.70) and 0.69 (95% CI: 0.66–0.73), respectively.</p> Conclusions <p>These findings suggest that metformin may lower long-term IDD risk in T2DM patients, particularly those with hypertension, highlighting its potential role in IDD prevention and the need for further interventional studies.</p>

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Impact of metformin on intervertebral disc degeneration in patients with diabetes: a prospective cohort study from the UK biobank

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月11日

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  • Jianan Chen,
  • Nianchun Liao,
  • Bo Gao,
  • Tongzhou Liang,
  • Wenjun Hu,
  • Zaoqiang Zhang,
  • Wangim Choi,
  • Huihong Shi,
  • Song Liu,
  • Yanbo Chen,
  • Youxi Lin,
  • Zhihuai Deng,
  • Xianjian Qiu,
  • Dongsheng Huang,
  • Wenjie Gao

摘要

Objective

Intervertebral disc degeneration (IDD) is a major contributor to low back pain and disability. Emerging evidence suggests that type 2 diabetes mellitus (T2DM) accelerates IDD progression, while metformin, a first-line treatment for T2DM, may offer protective effects. This study aimed to evaluate the association between metformin use and long-term IDD risk in T2DM patients using data from the UK Biobank.

Methods

A prospective cohort of 20,350 individuals with T2DM was analyzed, including 11,158 metformin users and 9192 non-users. The primary outcome was incident IDD, identified via ICD-10 codes. Cox proportional hazards models estimated hazard ratios (HRs) for IDD, adjusting for demographic, behavioral, and clinical factors. A sensitivity analysis was performed by excluding patients with a follow-up period of less than 2 years to assess the stability of the results. Subgroup and interaction analyses explored effect modifiers. Predictive models using Cox regression were developed to estimate 5- and 13-year IDD risk, with model performance evaluated by area under the ROC curve (AUC).

Results

Over a median follow-up of 13 years, metformin use was significantly associated with a reduced risk of IDD [HR (95% CI): 0.863 (0.753–0.989), p = 0.034]. The results were robust in the sensitivity analysis[HR (95% CI): 0.862 (0.749–0.992), p = 0.039]. A significant interaction with sleep time and hypertension status were observed (P for interaction < 0.05). Predictive model AUCs for 5- and 13-year IDD risk were 0.64 (95% CI: 0.57–0.70) and 0.69 (95% CI: 0.66–0.73), respectively.

Conclusions

These findings suggest that metformin may lower long-term IDD risk in T2DM patients, particularly those with hypertension, highlighting its potential role in IDD prevention and the need for further interventional studies.