Abstract Introduction GLP-1 receptor agonist is a medication class that mimics the endogenous incretin hormone GLP-1. Short-acting GLP-1 agents were studied as adjunct therapies in type 1 diabetes (T1DM) but not approved due to concern of increased diabetic ketoacidosis (DKA) risk. Long-acting GLP-1 medications are still commonly prescribed for T1DM patients. One study has assessed the impact of a long-acting GLP-1 in 11 T1DM patients. No hospitalizations were observed, and time in range was not reported. [1] Our study aims to evaluate the efficacy and safety of long-acting GLP-1 medications in a larger cohort of T1DM patients. Methodology We conducted a retrospective chart review of T1DM patients taking a long-acting GLP-1 for at least three months. ICD-10 code E10. Type 1 diabetes mellitus was used to search our institution's Electronic Health Record system (EPIC). Primary parameters collected included A1C and glycemic trends. Data analysis was done by averaging values over a two-year period before and after starting the medication. Results We identified 27 participants with T1DM (mean age 42yrs, mean T1DM duration 18.1yrs) on a long-acting GLP-1 (semaglutide 70.4%, dulaglutide 33.3%, long-acting exenatide 3.7%, albiglutide 3.7%). Mean therapy duration was 24.28±19. 01mo. A1C values decreased significantly from7.61±1. 08% to 7.16±0.73% (p=0. 015, N=25). Per CGM data, average time in range (TIR) increased significantly from48.82±22.35% to64.70±16.58% (p=0. 0002, N=15), average time in hyperglycemia decreased from42.39±23.32% to 31.58±16.65% (p=0. 019, N=14) and 14-day blood mean glucose decreased from 190.40±38.42 mg/dl to 167. 06±25.86 mg/dl (p=0. 001, N=17). There were no statistically significant differences in time in hypoglycemia and incidence of DKA. Hyperglycemic and hypoglycemic episodes were defined per patients’ individualized CGM settings (most commonly Blood Glucose levels>180 and <70 respectively). Patients’ weight decreased non-significantly from182. 00±50.92 lbs to 170.88±51.37 lbs (p=0.128, N=8). There were no ER visits or hospitalizations for DKA while on GLP-1 therapy. Conclusion There is an urgent need for strategies to improve glycemic control and reduce morbidity and mortality in T1DM. Long-acting GLP-1s are a promising adjunct to insulin. Our study is the first to demonstrate significant A1C reduction and TIR increase without increased hypoglycemia and DKA risk in 27 T1DM patients on long-acting GLP-1s. Longer prospective studies are warranted. Presentation: No date and time listed