Pos0048 Gout Risk in Prediabetic Adults Initiating Metformin

Background: Prediabetes is a major global public health concern, and current evidence supports the use of metformin in diabetes prevention. Despite the strong association between gout and prediabetes, the role of antidiabetic medications in gout among prediabetics remains uncertain. Objectives: This study aimed to compare the incidence rates of gout between prediabetic adults starting metformin and those 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). Eligible patients for the study cohort were aged ≥ 18 years, identified as prediabetics based on a glycated haemoglobin (HbA1c) level between 5.7% and 6.4%, and with no prior HbA1c measurements > 6.4%. We excluded those with a previous history of diabetes, a diagnosis of gout, or a prescription of urate-lowering therapies or colchicine. Patients who initiated metformin within 18 months after a prediabetes diagnosis were categorized as new users, while those who did not start metformin or other antidiabetic medications within this period were categorized as non-users. We used 1:n propensity score (PS) matching with a PS caliper of 0.05 to balance the baseline characteristics of the metformin-exposed and non-user groups. The index date was defined as the date of the first metformin prescription for new users, and for matched non-users, this same date was selected as their index date. Patients were followed from index date until the incidence of gout, incidence of diabetes, discontinuation of metformin, start of metformin by non-users, loss to follow-up, the end of the study period, or death, whichever occurred first. The primary outcome was incident gout, defined as at least two diagnoses of gout or one diagnosis plus the use of a medication typically prescribed for gout. Incidence rates (and 95% confidence intervals) of gout were estimated per 1000 person-years. Cox proportional hazards models estimated the hazard ratio comparing metformin initiators to non-users, adjusting for age, body mass index, HbA1c, hypertension and diuretic use. We performed subgroup analyses stratified by sex, age, estimated glomerular filtration rate (eGFR), and baseline diuretic use. Two separate linear regression analyses were performed to assess the association between metformin use and changes in serum urate or C-reactive protein (CRP). Results: We identified 25,064 adults with prediabetes. After exclusions, we PS matched 1,154 metformin initiators to 13,877 non-users of antidiabetic medication. Following the PS matching, all baseline characteristics were similar between metformin users and non-users, with standardized mean differences < 0.1. Median length of follow-up was 3.9 (IQR: 1.61 - 8.06) 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, with an HR of 0.68 (95% CI, 0.48 - 0.96) (Table 1). These results were consistent in subgroups (Figure 1). No relationship was found between metformin use and changes in serum urate or CRP. Conclusion: Among prediabetic adults initiating metformin, the risk of gout was reduced, as evidenced by a lower incidence rate and hazard ratio, and these findings remained consistent in subgroups. These results suggest that the selection of antidiabetic medications may play an important role in lowering the risk of gout in prediabetics. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Javier Marrugo: None declared, Leah Santacroce: None declared, Misti L. Paudel: None declared, Sho Fukui: None declared, Alexander Turchin AT serves as a consultant in areas unrelated to this research to Novo Nordisk and Proteomics International., AT receives salary support from unrelated research contracts to Brigham and Women's Hospital from Eli Lilly., Sara K. Tedeschi SKT reports consulting fees from Novartis., Daniel H. Solomon DHS receives salary support from unrelated research contracts to Brigham and Women's Hospital from CorEvitas, Janssen, and Novartis.