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.