1737-P: Efficacy, Glycemic Variability, and Safety of Insulin Icodec Combined with Semaglutide in Simplifying Complex Polypharmacy for Uncontrolled Type 2 Diabetes: A Retrospective Study

Introduction and Objective: Treatment burden from complex polypharmacy (≥3 glucose-lowering agents) compromises adherence in type 2 diabetes (T2D). This study investigated whether switching to a simplified dual therapy of once-weekly insulin icodec and semaglutide could maintain or improve glycemic control while reducing therapeutic complexity. Methods: Retrospective analysis of 66 adults with T2D (HbA1c ≥7.0%) from Zhujiang Hospital of Southern Medical University (Oct 1-Dec 15, 2025) previously on ≥3 glucose-lowering agents. After 3-day baseline continuous glucose monitoring (CGM) on original therapy, participants initiated dual therapy: icodec (equivalent to 0.2 IU/kg/day×7 days ×1.5, ±20 IU/week adjustment) and semaglutide (0.25 mg/week). Primary outcomes: CGM data were compared between first/last 3 days of original vs dual therapy. Time-In-Range (TIR) improvement (paired t-test) and time to achieve TIR ≥70% (Kaplan-Meier analysis). Secondary outcome: hypoglycemia incidence (ADA Levels 1-3) and gastrointestinal adverse events. Results: Participants (mean age 61.8 ± 9.0 years; 51.5% male) had baseline characteristics: HbA1c 8.1% (IQR 7.5-8.8), fasting C-peptide 2.98 μg/L (IQR 2.15-3.82), mean body weight 72.8 ± 11.5 kg, with preserved β-cell function (via fasting C-peptide). The mean initiation dose of icodec was 185.8 ± 41.2 IU/week. Following the initiation of dual therapy, TIR improved significantly from 54.8±23.3% at baseline to 78.1±18.9% (95% CI 9.5-25.5, P<0.001). Median time to 70% TIR: 3.0 days (95% CI: 2.0-5.0). Two mild hypoglycemic events (ADA Level 1) occurred in 2 participants (3.03%), both self-resolved within 2 weeks without dose adjustments. No gastrointestinal adverse events were observed. Conclusion: Icodec combined semaglutide dual therapy provides simplified, safe, effective glycemic management, a promising therapeutic option for T2D patients with suboptimal glycemic control on complex polypharmacy. Disclosure X. Zhu: None. X. Li: None. J. Sun: None. Funding Supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project (Main Project No. 2024ZD0524500; Subproject No. 2024ZD0524504) and the Open Fund of the National Innovation Center for High-Performance Medical Devices (Proj No. NMED2023AGP-012)