Session Two: Changing the Type 2 Diabetes Mellitus Management Paradigm with Fixed-Ratio Combinations

Abstract

Fixed-ratio combinations, the co-administration of two injectable therapies in a formulation that can be adjusted through titration, are changing the Type 2 diabetes mellitus management paradigm. Current treatment guidelines for glucose control rely heavily on a stepwise approach; however, that can be inconsistently followed and relatively indifferent to the complex pathophysiology of Type 2 diabetes mellitus. Fixed-ratio combinations have targeted actions that complement other treatments. Basal insulin plus a glucagon-like peptide 1 receptor agonist (GLP-1 RA) represent one such combination that offers an efficacious approach to control both fasting and postprandial glucose, key determinants of glycaemic and clinical outcomes. Two fixed-ratio combinations, insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) and insulin degludec plus liraglutide (IDegLira), are currently available in the European Union (EU) and USA. Clinical evidence from pivotal, Phase III trials with iGlarLixi and IDegLira have demonstrated their robust glycated haemoglobin (HbA1c)-lowering effects, which are associated with mitigation of side effects commonly experienced with the individual components, including basal insulin-related body weight gain and GLP-1-related gastrointestinal adverse events. The spectrum of clinical benefits associated with these titratable fixed-ratio combinations may offer a more compelling case for earlier and effective use of these therapies that better addresses the complex underlying pathophysiology of Type 2 diabetes mellitus.