Titratable fixed‐ratio combination of basal insulin plus a glucagon‐like peptide‐1 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes

Abstract

Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon-like peptide-1 receptor agonist (GLP-1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real-world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed-ratio combinations (FRCs) of basal insulin and GLP-1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta-analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head-to-head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP-1 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP-1 RAs as an alternative treatment option.basal insulin, GLP-1 analogue, glycaemic control, insulin therapy, type 2 diabetes | INTRODUCTIONDespite advancements in type 2 diabetes (T2D) therapy, a considerable proportion of people with diabetes fail to reach standard and individualized glucose targets. A recent meta-analysis of global glycaemic control using 24 studies across 20 countries showed that the pooled average proportion of people with T2D achieving their HbA1c targets was 43%, both in primary and secondary care settings. 1 Similarly, the International Diabetes Management and Practices Study (IDMPS), a large observational, cross-sectional, real-world study in

Real-Time Flash Glucose Monitoring Had Better Effects on Daily Glycemic Control Compared With Retrospective Flash Glucose Monitoring in Patients With Type 2 Diabetes on Premix Insulin Therapy

“…The MOSAIc study of 18 countries showed that about 30% of people with T2DM taking insulin were using premix insulin globally, and the percentage was 67% in China (11). However, several real-world studies have shown that glycemic control remains unsatisfactory 6-12 months after initiating or switching therapy with premix insulin (12)(13)(14). The reasons of poor glycemic control in patients on premix insulin include fear of weight gain and hypoglycemia and the need for frequent selfmonitoring of blood glucose (12).…”

“…However, several real-world studies have shown that glycemic control remains unsatisfactory 6-12 months after initiating or switching therapy with premix insulin (12)(13)(14). The reasons of poor glycemic control in patients on premix insulin include fear of weight gain and hypoglycemia and the need for frequent selfmonitoring of blood glucose (12). FGM may be a good solution to these problems.…”

Expert Panel Guidance and Narrative Review of Treatment Simplification of Complex Insulin Regimens to Improve Outcomes in Type 2 Diabetes

“…However, a high proportion of people with suboptimal controlled T2D display low rates of achieving acceptable glycaemic control whilst receiving these insulin preparations [46,47]. Premixed insulins also carry an increased risk of weight gain and hypoglycaemia compared with other strategies, such as an FRC [48], and individuals often do not experience any additional clinical benefit when switched to premixed preparations from other insulin regimens [49][50][51].…”

Practical Guidance on Basal Insulin Initiation and Titration in Asia: A Delphi-Based Consensus

“…In this regard, fixed-ratio combinations (FRCs) of basal insulin and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) provide a novel alternative. The FRCs-insulin degludec/liraglutide and insulin glargine/lixisenatide-have a more physiological mode of action, as they target both postprandial and prandial glucose levels [50][51][52]. The FRCs might be an option for initiation in individuals with high postprandial glycemic surges, which are typically observed in the Asian population [30,51,52].…”