Comparative Effectiveness of Glucagon-like Peptide-1 Receptor Agonists Versus Oral Agents for Insulin Discontinuation in Type 2 Diabetes : A Target Trial Emulation.

BACKGROUND: Addition of glucagon-like peptide-1 receptor agonists (GLP-1RAs) to basal insulin can decrease insulin requirements, but whether it permits insulin discontinuation is unclear. OBJECTIVE: To compare rates of insulin discontinuation among patients with type 2 diabetes (T2D) receiving basal insulin who initiated treatment with a GLP-1RA, sodium-glucose cotransporter-2 inhibitor (SGLT-2i), or dipeptidyl peptidase-4 inhibitor (DPP-4i) between 2020 and 2022. DESIGN: Target trial emulation. SETTING: U.S. Veterans Health Administration electronic health record (EHR) data. PARTICIPANTS: Veterans with T2D receiving basal insulin. MEASUREMENTS: Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up. RESULTS: Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A (HbA) level of 9% or more. Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compared with the SGLT-2i and DPP-4i arms, respectively). Results were not substantively different in a modified per protocol analysis. None of the subgroups showed a comparative advantage of GLP-1RAs with respect to insulin discontinuation over SGLT-2is or DPP-4is. LIMITATION: Possible residual confounding; misclassification of exposure and outcome using EHRs may bias associations toward the null. CONCLUSION: Among veterans with T2D receiving basal insulin therapy, addition of GLP-1RA did not increase the chances of stopping insulin therapy compared with SGLT-2i or DPP-4i therapy. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.