GLP-1RAs did not improve insulin discontinuation rates versus SGLT-2i or DPP-4i in T2D veterans

For patients with Type 2 Diabetes (T2D) on basal insulin, reducing or discontinuing insulin therapy is a significant clinical goal, often associated with improved quality of life and reduced risk of hypoglycemia. While glucagon-like peptide-1 receptor agonists (GLP-1RAs) are known to decrease insulin requirements and improve glycemic control, their comparative effectiveness in enabling complete insulin discontinuation versus other oral agents like sodium-glucose cotransporter-2 inhibitors (SGLT-2i) or dipeptidyl peptidase-4 inhibitors (DPP-4i) has remained unclear. This gap in understanding impacts treatment strategies for T2D patients aiming to simplify their regimen.

Researchers conducted a target trial emulation using U.S. Veterans Health Administration electronic health record (EHR) data from 2020-2022. The study included 8869 matched sets of veterans with T2D receiving basal insulin who initiated either a GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, 0.3% exenatide), an SGLT-2i (99.7% empagliflozin), or a DPP-4i (95.9% alogliptin). The primary endpoint was insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up. Data was analyzed using an intention-to-treat approach.

Among the 8869 matched sets, the study found no significant comparative advantage for GLP-1RAs in achieving insulin discontinuation. Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators discontinued insulin therapy. This was comparable to 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators. The risk ratio for the GLP-1RA arm compared with the SGLT-2i arm was 0.93 (95% CI, 0.86 to 1.01), and compared with the DPP-4i arm, it was 0.98 (CI, 0.87 to 1.09). Both confidence intervals crossed 1.0, indicating no statistically significant difference. Subgroup analyses also failed to show a comparative advantage for GLP-1RAs over SGLT-2is or DPP-4is regarding insulin discontinuation.

The intention-to-treat analysis showed that GLP-1RA initiators had a 16.7% rate of insulin discontinuation, which was not statistically different from SGLT-2i initiators (17.9%) or DPP-4i initiators (17.1%).