Fixed Ratio Combination - Pro Perspective

1Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) and Centro de Investigación Biomedicaen Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
2Department of Cardiovascular and Metabolic Diseases, IRCCS Multimedica, Sesto San Giovanni (MI), Italy.

Type 2 diabetes (T2D) represents an escalating burden worldwide. Since postprandial hyperglycemia contributes significantly to total glycemic burden and is associated with heightened cardiovascular risk, targeting PPG early in T2D is paramount. Premixed insulin regimens are widely used in the world due to their convenience and effectiveness. Data from randomized controlled trials and observational studies comparing efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) with biphasic insulin lispro mix (LM 25/50) and versus other insulin therapies or oral antidiabetic drugs (OADs) in T2D demonstrated that BIAsp 30 and LM 25/50 were associated with similar or greater improvements in glycemic control versus comparator regimens, such as basal-bolus insulin, in insulin-naive, and prior insulin users. Studies directly comparing BIAsp 30 and LM 25 provided conflicting glycemic control results. Safety data generally showed increased hypoglycemia and weight gain with premixed insulins versus basal-bolus insulin or OADs. However, large observational trials documented improvements in glycated hemoglobin, PPG, and hypoglycemia with BIAsp 30 in multi-ethnic patient populations. In summary, this evidence demonstrates that premixed insulin regimens are an appropriate and effective treatment choice in T2D. More recently two other co-formulations reached the market: long acting insulin plus GLP-1RA (Glargine + Lixisenatide and Degludec + Liraglutide) and Insulin Degludec + Insulin Aspart. The co-formulations between basal insulin and GLP-1RA have shown a superiority in improving metabolic control versus the each single components alone. Interestingly, the co-formulation between Degludec + Liraglutide has recently shown to be comparable to the basal bolus regimen. Similar results have been obtained with the combination of Insulin Degludec + Insulin Aspart.