1886-P: Efficacy and Safety Noninsulin Hypoglycemic Drugs as Adjunctive Therapy to Automated Insulin Delivery System in Type 1 Diabetes: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Introduction and Objective: Efficacy of adding non-insulin hypoglycemic drugs to automated insulin delivery (AID) systems in patients with type 1 diabetes (T1D) was investigated in randomized controlled trials (RCTs) yet no meta-analysis has been conducted. This study aimed to systematically analyze the existing evidence. Methods: Four datasets were searched up to 31st August 2025. Inclusion criteria were: T1D populations of any age; comparing any type of non-insulin hypoglycemic drug added to AID systems or not; reporting primary outcomes (time in range 70-180 mg/dL; TIR). Results were pooled using a random-effect meta-analysis. Risk of bias was assessed using Cochrane RoB2 tool. Quality of evidence was assessed by GRADE approach. Results: Nine RCTs met inclusion criteria, investigating SGLT-2 inhibitors (N=5), GLP-1 receptor agonists (N=2), and DPP-4 inhibitors (N=2) respectively. Overall, these drugs with AID systems improved TIR by +10.0 % (7.4 to 12.6%) and time in tight range (70-140 mg/dL; TITR) by +8.9% (6.8 to 11.0%) with I 2 of 60.4% and 15.4% (P <0.001). These improvements were primarily driven by reductions in time above range >250 mg/dL (-4.3 [-5.8 to -2.8] %, time above range >180 mg/dL (-11.6 [-14.7 to -8.5] %) and coefficient of variation (-2.9 [-4.5 to -1.4] %) without increased hypoglycemia. Daily insulin dose decreased by 8.9 units. Among these, SGLT-2 inhibitors conferred the greatest TIR improvement (+12.5%), followed by GLP-1 receptor agonists (+7.1%) and DPP-4 inhibitors (+6.4%). No significant differences were found in severe hypoglycemia (SH) and diabetic ketoacidosis (DKA). Conclusion: SGLT-2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists may serve as effective and safe adjuncts for T1D individuals using AID systems, offering improvements in time in range, reductions in hyperglycemia, reduced insulin requirements without evidence of increasing DKA and SH. Disclosure Y. Zhou: None. M. Lei: None. Q. Lin: None. Y. Ni: None. Z. Lin: None. D. Yang: None. C. Wang: None. W. Xu: None. J. Yan: None. Funding Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0508200, 2023ZD0508203)