Background and aims: iDegLira, a fixed-ratio combination of insulin degludec-liraglutide, indicated for the treatment of T2DM, has demonstrated efficacy in glycemic control in previous studies. However, there is a paucity of published data regarding its impact on Time-in-Range (TiR). Ti-REX (TiR Evaluation in Xultophy therapies) is a retrospective, multi-center, observational, “pre-post” cohort study conducted in 5 clinical centers in Lombardy. Its aim was to utilize intermittently scanned continuous glucose monitoring (is-CGM) to observe changes in TiR among T2DM patients before and after initiating iDegLira treatment, thereby evaluating the efficacy of is-CGM as a tool for monitoring clinical interventions. The study included all adults consecutively identified in medical records who commenced treatment with iDegLira and for whom an is-CGM report before and after initiation of iDegLira was available. Time in range (TIR) represented the primary endpoint, with additional assessment of glucometric indices, insulin doses, and body weight. Methods: A total of 87 patients were included (mean age 70.2±11.0 years, mean duration of T2D 15.5±9.6 years; BMI 29.4±5.4 kg/m2, baseline HbA1c 9.1±2.1%, 33% insulin naïve, 20.7% treated with basal-oral therapy (BOT), and 46% treated with multiple daily injections of insulin (MDI)). Following an average of 1.7 weeks from initiation of iDegLira, TIR significantly increased from 56.8±23.5% to 81.3±13.5% (p<0.0001), while time above range (TAR) decreased from 42.3±24.2% to 17.1±13.6% (p<0.0001); time below range (TBR) remained consistently low (from 1.3±2.3% to 1.4±2.6%; p=0.62). Estimated HbA1c decreased from 9.1±2.1% to 6.7±0.6% (p<0.0001), and the percentage of patients with a coefficient of variation of blood glucose ≥36% decreased from 33.2% to 13.8% (p=0.0005). Notably, among patients on MDI, there was a substantial reduction in total insulin dose (from 55.8±31.2 IU to 27.2±12.3 U). Conclusions: In patients with poorly controlled T2D, whether insulin naïve or receiving BOT or MDI, initiation of iDegLira significantly increased time spent in optimal metabolic control and markedly reduced glycemic fluctuations. Furthermore, the utility of is-CGM as a comparative monitoring tool was observed. Extended case-control studies are warranted to validate these findings.