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

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. 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). 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. 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.