Treatment intensification following glucagon-like peptide-1 receptor agonist in type 2 diabetes: Comparative effectiveness analyses between free vs. fixed combination of GLP-1 RA and basal insulin. RESTORE-G real-world study

• Published in: Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2024-08, Vol.34 (8), p.1846-1853
• Main Authors: Candido, Riccardo, Nicolucci, Antonio, Larosa, Monica, Rossi, Maria Chiara, Napoli, Raffaele, Gabellieri, Enrico, Tortato, Elena, Rabini, Rosa Anna, Crazzolara, Dalia, Lucibelli, Luigi, Aragiusto, Concetta, Panzolato, Gianluigi, Di Mauro, Maurizio, Del Buono, Andrea, Placentino, Giuseppe, Di Cianni, Graziano, Brandoni, Gabriele, Fazion, Stefano, Gregori, Giovanna, Di Benedetto, Antonino, De Riva, Carlo, Terracciano, Annamaria, Zenari, Luciano, Cavalot, Franco, Porcellati, Francesca, Anichini, Roberto, Citro, Giuseppe, D'Angelo, Paola, Arca, Marcello, Morviducci, Lelio, Montani, Valeria, Fiorentini, Paolo
• Format: Article
• Language: English
• Subjects: Aged; Basal insulin; Biomarkers - blood; Blood Glucose - drug effects; Blood Glucose - metabolism; Comparative Effectiveness Research; Degludec 100; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - drug therapy; Drug Combinations; Drug Substitution; Effectiveness; Electronic Health Records; Female; Fixed-ratio combination; Glargine 300; GLP-1 receptor agonists; Glucagon-Like Peptide-1 Receptor - agonists; Glycated Hemoglobin - metabolism; Glycemic Control - adverse effects; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; iDegLira; iGlarLixi; Incretins - adverse effects; Incretins - therapeutic use; Insulin Glargine - administration & dosage; Insulin Glargine - adverse effects; Insulin Glargine - therapeutic use; Insulin, Long-Acting - administration & dosage; Insulin, Long-Acting - adverse effects; Insulin, Long-Acting - therapeutic use; Italy; Liraglutide - adverse effects; Liraglutide - therapeutic use; Male; Middle Aged; Naïve; Retrospective Studies; Safety; Time Factors; Treatment Outcome; Type 2 diabetes
• ISSN: 0939-4753; 1590-3729; 1590-3729
• DOI: 10.1016/j.numecd.2024.03.023

Add-on of basal insulin (BI) to intensify the ongoing therapy with glucagon-like peptide 1 receptor agonist (GLP-1 RA) is recommended, but it is unclear if free or fixed combination of BI and GLP-1 RA produce similar outcomes. A retrospective comparative effectiveness analysis of the add-on of glargine 300 U/mL (Gla-300) to ongoing GLP-1 RA vs. switch to fixed ratio combination of degludec and liraglutide (iDegLira) was performed. Real-world data collected in electronic medical records by 32 Italian diabetes clinics. Propensity score (PS) adjustment was applied to assess changes in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), body weight, and BI dose after 6 months from Gla-300 or iDegLira initiation. Compared to iDegLira group (N = 260), Gla-300+GLP-1 RA group (N = 255) had older age and higher levels of HbA1c (9.1 vs. 8.9%). After 6 months, statistically significant greater FBG improvement [estimated mean difference and 95% confidence intervals: −24.05 mg/dl (−37.04; −11.06; p = 0.0003) and BI dose increase [+0.03 U/kg (95%CI 0.00; 0.06); p = 0.009] were found in the free vs. fixed combination group, although low doses of BI (0.2 U/kg) were reached in both groups. Trends of larger HbA1c and body weight reductions with the free combination were also found, without reaching the statistical significance. Although inertia in insulin initiation and titration was documented in both groups, higher benefit on FBG control was obtained with free vs. fixed combination, likely due to a better titration of BI and GLP-1 RA. •Addition of basal insulin (BI) to GLP-1 RA is a recommended intensification approach.•It is unclear if starting BI in free or fixed combination with GLP-1 RA produce similar results.•Larger benefit on fasting blood glucose was obtained with free vs. fixed combination.•A better titration of BI and GLP-1 RA was documented with the free combination.•Clinical inertia in titration was documented in both approaches.