2875-LB: Effectiveness and Safety of Adjunctive Therapy in Classic Type 1 Diabetes: A Real-World Cohort Study

Introduction and Objective: In classic type 1 diabetes, insulin alone often fails to achieve optimal glycemic control, balancing microvascular complications against hypoglycemia risk. Although adjunctive glucose-lowering agents have shown promise in trials, real-world evidence on their effectiveness and safety is limited. This study aimed to compare insulin monotherapy versus insulin plus adjunctive therapy in improving glycemic control, preserving islet function, and ensuring safety Methods: This retrospective cohort study used the Tianjin Diabetes and Health Cohort (2017-2024). Patients with classic T1D were included, excluding other diabetes types such as LADA. Two groups were defined: insulin monotherapy vs. insulin plus adjunctive therapy (SGLT2i, GLP-1RA, metformin, or DPP4i). Propensity score matching (1:1) balanced baseline variables (HbA1c, fasting C-peptide, disease duration, complications, age, sex). Primary outcomes were HbA1c <7%, ΔHbA1c, and Δfasting C-peptide. Safety outcomes included hospitalization for hypoglycemia and ketosis/DKA. Logistic regression and ANCOVA were used Results: Of 1,004 patients initially enrolled (201 insulin monotherapy, 803 insulin plus adjunctive therapy), 312 were included after 1:1 matching. Mean age was 39-40 years, baseline HbA1c 9.6%-9.8%, and fasting C-peptide 0.4-0.7 ng/mL. Median follow-up was 2.8 years. Baseline variables were well balanced after matching (SMD < 0.1). The adjunctive therapy group had significantly higher HbA1c target attainment (OR=1.73, P=0.030). Adjusted mean change in fasting C-peptide was −0.0596 (95% CI: −0.160 to 0.0406) in monotherapy group and −0.0798 (95% CI: −0.178 to 0.0179) in adjunctive group (between-group difference 0.0202, P=0.7774). No significant differences were found in safety outcomes Conclusion: In this real-world cohort of classic type 1 diabetes, insulin plus adjunctive therapy significantly improved glycemic control versus insulin alone, with no between-group difference in islet function preservation or safety Disclosure J. Zhang: None. Z. Song: None. H. Zhu: None. M. Li: None. J. Chang: None. W. Yang: None. Y. Duan: None. H. Mei: None. T. Wu: None.