Introduction and Objective: The GRADE trial compared four glucose-lowering drugs for HbA1c reduction in individuals with type 2 diabetes mellitus (T2DM) on metformin monotherapy but lacked a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) arm. We emulated GRADE including SGLT-2i & excluding insulin.Methods: In a US commercial claims database (2014-2023), we used propensity score weighting to balance 87 baseline covariates in eligible patients (T2DM, age ≥30 years, on metformin monotherapy, baseline HbA1c 6-9%); 5,489 initiated SGLT-2i, 3,617 glucagon-like peptide-1 receptor agonists (GLP-1RA), 5,069 dipeptidyl peptidase 4 inhibitors (DPP-4i), & 11,148 sulfonylureas (SU). We estimated HR & 95% CI for primary (HbA1c ≥7%) & secondary outcomes (major adverse cardiovascular events (MACE), heart failure hospitalization (HHF), severe hypoglycemia).Results: GLP-1RA had the lowest risk of primary outcome (HR 0.63;0.58-0.68, HR 0.71;0.65-0.76, and HR 0.67;0.61-0.72 vs. SGLT-2i, SU, and DPP-4i, respectively). SGLT-2i had risk comparable to DPP-4i (HR 1.06;0.99-1.13) but higher than SU (HR 1.12;1.06-1.18). MACE outcome had no differences but SGLT-2i had reduced HHF risk vs. SU. Hypoglycemia was rare with the highest risk for SU.Conclusion: When added to metformin in patients with T2DM, GLP-1RA achieved better glycemic control than SU and DPP-4i, as seen in GRADE, and vs. SGLT-2i.
A. Ray: None. S. Kattinakere Sreedhara: None. J.M. Paik: None. S. Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies. Advisory Panel; Alexion Pharmaceuticals, Inc. Consultant; Wolters Kluwer Health, Patient Square Capital. K. Bykov: None. G. Hahn: None. D.J. Wexler: Other Relationship; Novo Nordisk. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.
Patient Centered Outcomes Research Institute (DB-2020C2-20326)
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