Time to Treatment Intensification with Glucagon-Like Peptide-1 Receptor Agonists Versus Comparators in People with Type 2 Diabetes Treated with Metformin.

Introduction: Treatment intensification is often required to attain glycemic targets in people living with type 2 diabetes (T2D) but can introduce regimen complexity and increase medication burden. Whether rates of treatment intensification differ by glucose-lowering medication class is unclear. This study investigated comparative treatment durability of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus standard T2D treatments, with implications for longitudinal risk mitigation and the need for treatment intensification.

Methods: This retrospective cohort study used US ambulatory electronic medical record data from January 2006 to November 2021 (covering market availability of first-generation GLP-1RAs) to assess time-to-treatment intensification following initiation of treatment with GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is), dipeptidyl peptidase-4 inhibitors (DPP-4is), and sulfonylureas (SUs) in 1:1 propensity score-matched adults living with T2D treated with metformin. The primary outcome was the time to treatment intensification (i.e., initiation of a third glucose-lowering medication). Secondary outcomes included change in glycated hemoglobin (HbA) level and body mass index (BMI) at 12 months after treatment initiation.

Results: Overall, 59,958 participants were included in this study (GLP-1RA [n = 11,933], SGLT2i [n = 13,726], DPP-4i [n = 14,415], SU [n = 19,884]). Initiation of treatment with GLP-1RAs was associated with a significantly lower rate of initiation of a subsequent glucose-lowering medication compared with SGLT2is (hazard ratio [HR]: 0.93 [95% confidence interval, CI, 0.88, 0.97]; p = 0.001), DPP-4is (HR: 0.77 [95% CI 0.74, 0.81]; p < 0.001), and SUs (HR: 0.84 [95% CI 0.80, 0.88]; p < 0.001). After 12 months, GLP-1RA treatment led to a significantly greater reduction in HbA compared with SGLT2i (p = 0.005), DPP-4i (p < 0.001), and SU (p < 0.001) treatment. GLP-1RA treatment was also associated with significantly greater reductions in BMI after 12 months compared with DPP-4i and SU treatment (both p < 0.001) but not compared with SGLT2i treatment.

Conclusion: These data suggest that among people living with T2D treated with metformin who require a second glucose-lowering therapy, GLP-1RAs may reduce or delay the need for further treatment intensification versus other standard glucose-lowering therapies.