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

Authors

Kasia J Lipska, Kelson Zawack, Lei Yan, Pradeep Mutalik, Jingmao Li, Barbara Gulanski, George N Ioannou, Mihaela Aslan

Published in

Annals of internal medicine. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

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.
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.
Target trial emulation.
U.S. Veterans Health Administration electronic health record (EHR) data.
Veterans with T2D receiving basal insulin.
Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up.
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_1c (HbA_1c) 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.
Possible residual confounding; misclassification of exposure and outcome using EHRs may bias associations toward the null.
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.
U.S. Department of Veterans Affairs.

PMID:
42441965
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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