Introduction and Objective: Metformin is commonly used off-label for prediabetes; however, other antihyperglycemic drug classes may provide greater weight loss and metabolic benefits. This real-world evidence (RWE) analysis compared the efficacy of GLP-1 receptor agonists (GLP-1RAs), dual GIP/GLP-1 receptor agonists (GIP/GLP-1RAs), and sodium glucose cotransporter 2 inhibitors (SGLT2i) to metformin for diabetes prevention.Methods: This retrospective cohort study used TriNetX national EHR repository. Patients were aged ≥ 18 years, had a prediabetes diagnosis, and were prescribed monotherapy with metformin or other antihyperglycemics (SGLT2i, GLP-1RAs, GIP/GLP-1RAs) within 3 months of prediabetes diagnosis. Individuals with prior diabetes were excluded. Each of the treatment cohorts underwent 1:1 propensity matching to the metformin cohort based on demographics, comorbidities, laboratory data, and cardiometabolic medications. The primary outcome was incident diabetes at 3 years following antihyperglycemic initiation. Hazard ratios (HR) were estimated using Kaplan-Meier analysis.Results: Compared to metformin, GLP-1RAs and GIP/GLP-1RAs were associated with a significantly lower risk of incident type 2 diabetes (n = 32,520; HR, 0.55; 95% CI, 0.53-0.58; p<0.0001) and (n = 11,660; HR, 0.47; 95% CI, 0.43-0.52; p<0.001) respectively. SGLT-2 inhibitors also demonstrated risk reduction for incident diabetes (n=5,201; HR, 0.75; 95% CI, 0.69-0.82; p<0.0001).Conclusion: In this RWE analysis, GLP-1RAs, GIP/GLP-1RAs, and SGLT2i were associated with reduced T2D incidence compared to metformin. However, GIP/GLP-1RAs provided the largest reduction in the incidence of T2D. Further cost-effectiveness analyses are warranted to determine the role of these therapies for diabetes prevention.
G.M. Siew: None. A. Astavans: None. N. Mathioudakis: None.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK R01DK125780)
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