Background: Fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists have emerged as an effective strategy for treatment intensification in type 2 diabetes mellitus (T2DM). However, long-term real-world data on their metabolic, β-cell, and renal effects remain limited. This study aimed to evaluate the 12-month real-world outcomes of insulin glargine/lixisenatide (iGlarLixi) therapy. Methods: This retrospective observational study included 78 patients with T2DM who were initiated on iGlarLixi and followed for 12 months. Clinical and laboratory parameters were assessed at baseline, 3 months, and 12 months. Changes in anthropometric, glycemic, biochemical, and renal parameters were analyzed. Early (3-month) changes were evaluated as predictors of long-term outcomes using correlation and receiver operating characteristic (ROC) analyses. Results: Median HbA1c decreased from 9.0% to 8.2% at 12 months (p = 0.015), with clinically meaningful improvement (≥1% reduction) observed in 21 (26.9%) patients. Body weight decreased significantly from 93.0 kg to 89.5 kg (p < 0.001). C-peptide levels increased from 2.46 to 3.00 ng/mL (p = 0.016). Median albumin-to-creatinine ratio (ACR) showed statistically significant paired changes; however, group-level median values remained similar over time. A reduction in albuminuria was observed in 34 (54.8%) of patients with available paired data. Exploratory ROC analyses suggested that early changes in body weight (AUC: 0.82), HbA1c (AUC: 0.74), and C-peptide (AUC: 0.76) may be associated with long-term outcomes. A combined model incorporating early weight and C-peptide changes showed improved exploratory predictive performance (AUC: 0.88). Conclusions: In a real-world setting, iGlarLixi therapy was associated with significant improvements in glycemic control and body weight, along with increased C-peptide levels that may reflect improved endogenous insulin secretion. While group-level renal changes were modest, individual-level improvements in albuminuria were observed in a substantial proportion of patients. Early treatment responses may serve as practical predictors of long-term outcomes, supporting a personalized approach to diabetes management. These findings should be interpreted in the context of concomitant therapies and comorbidities that may have influenced metabolic and renal outcomes in routine clinical practice.
