Treatment intensification following glucagon‐like peptide‐1 receptor agonists in type 2 diabetes: Comparative effectiveness analyses between different basal insulins. RESTORE‐G real‐world study

Abstract Aim: To compare the effectiveness of different basal insulins (BI) prescribed as an add-on to or switch from glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy. Materials and Methods: Retrospective, real-world data from electronic medical records of 32 Italian diabetes clinics were used, after propensity score adjustment, to compare effectiveness after 6 months of treatment with second- versus first- generation BI (2BI vs. 1BI) or glargine 300 U/ml versus degludec 100 U/ml (Gla-300 vs. Deg-100), when added to (ADD-ON) or in substitution of (SWITCH) GLP-1 RA. Only comparisons, including a minimum of 100 patients per group, were per- formed to ensure adequate robustness of the analyses. Results: In the ADD-ON cohort (N = 700), greater benefits of 2BI versus 1BI were found in glycated haemoglobin {HbA1c; estimated mean difference: 0.32% [95% confidence interval (CI) 0.62; 0.02]; p = .04} and fasting blood glucose [FBG; 20.73 mg/dl (95% CI 35.62; 5.84); p = .007]. In the SWITCH cohort (N = 2097), greater benefits of 2BI versus 1BI were found in HbA1c [ 0.22% (95% CI 0.42; 0.02); p = .03], FBG [ 10.15 mg/dl (95% CI 19.04; 1.26); p = .03], and body weight [ 0.67 kg (95% CI 1.30; 0.04); p = .04]. In the SWITCH cohort starting 2BI (N = 688), marked differences in favour of Gla-300 versus Deg-100 weredocumented in HbA1c [ 0.89% (95% CI 1.26; 0.52); p < .001] and FBG [ 17.89 mg/dl (95% CI 32.45; 3.33); p = .02]. Using propensity score matching as a sensitivity analysis, the benefit on HbA1c was confirmed [ 0.55% (95% CI –1.02; 0.08); p = .02]. BI titration was suboptimal in all examined cohorts. Conclusions: 2BI are a valuable option to intensify GLP-1 RA therapy. Switching to Gla-300 versus Deg-100 was associated with greater HbA1c improvement.