Prediabetes and Gout Risk: The Role of Metformin Use and Longitudinal Serum Urate Analysis

Abstract

Background: Despite the strong association between gout and prediabetes, the role of antidiabetic medications in managing gout among individuals with prediabetes remains uncertain. We estimated the incidence of gout and additionally compared the survival distribution of gout development in prediabetic patients starting metformin with prediabetic patients not using any antidiabetic treatments. Methods: We conducted a new-user, propensity score-matched cohort study using electronic health record data from an academic health system (2007-2022). Prediabetics were defined based on haemoglobin A1c levels. Metformin users were identified and followed from the first metformin prescription date. Non-users of antidiabetic medications were matched to metformin users based on propensity score and the start of follow-up. The primary outcome was incident gout. Cox proportional hazards models estimated the hazard ratio for metformin. Linear regression analyses assessed the association between metformin use and changes in serum urate (SU) or C-reactive protein (CRP). Results: We identified 25,064 prediabetics and propensity score-matched 1,154 metformin initiators to 13,877 non-users. Baseline characteristics were well balanced (all standardized mean differences .1). Median follow-up was 3.9 years. The incidence rate of gout per 1000 person-years was lower in metformin users 7.1 (95% CI 5.1 to 10) compared to non-users 9.5 (95% CI 8.8 to 10.2). Metformin initiation was associated with a reduced relative risk of gout (HR 0.68, 95% CI 0.48 to 0.96). No relationship was found between metformin use and changes in SU or CRP. Conclusions: Metformin use was associated with a lower risk of gout among patients with prediabetes, suggesting that treatment with metformin may have a role in lowering the risk of gout in individuals with prediabetes. Keywords: Gout, incidence, crystal arthropathies