The Effect of Metformin Adherence on the Reduction of Fracture Risk Among Type 2 Diabetes Patients

OBJECTIVES: Previous studies have indicated a positive impact of metformin (MET) use on bone mineral density in diabetic patients. However, adherence to MET can be challenging due to various factors. Despite this, the flexibility of adherence has been scarcely addressed. The objective of this study is to investigate whether strict adherence to the concurrent use of MET is associated with a reduced risk of fractures among individuals with type 2 diabetes mellitus (T2DM).

METHODS: A cohort study using the National Health Insurance Database from 2014 to 2020 focused on individuals aged 50 or above with T2DM. It included participants using metformin (MET) alongside second-line oral diabetes drugs, excluding those with a history of fractures. MET adherence was assessed by a medication possession ratio (MPR) over 40% within a year; those discontinuing MET were classified as non-adherent. Fractures were identified using diagnosis codes from outpatient and inpatient data. Propensity score matching (PSM) balanced covariates between the adherence and non-adherence groups. The study used a competing risk model to estimate the association between MET adherence and fracture risk, considering death as a competing risk. The Taipei Hospital's Institutional Review Board (IRB) approved the study protocol (TH-IRB-0023-0016).

RESULTS: After 1:1 PSM, 38,011 patients (both MET-adherent and non-adherent) were analyzed. The cohort comprised approximately 55% males, with 67% aged between 50-64. MET-adherent patients showed a lower risk of all fractures compared to non-adherent individuals, with an adjusted sub-hazard ratio (aSHR) of 0.76 (95% CI: 0.69-0.83), considering a 90-day discontinuation gap. This trend was consistent for major osteoporotic fractures (aSHR=0.78, 95% CI: 0.70-0.88). Similar results were noted in the 45-day gap scenario, where the aSHR for all fractures was 0.82 (95% CI: 0.73-0.91).