Initiating Titratable Fixed-Ratio Combinations of Basal Insulin Analogs and Glucagon-Like Peptide-1 Receptor Agonists: What You Need to Know

Abstract

Titratable fixed-ratio combinations (FRCs) of a basal insulin and a glucagon-like peptide-1 (GLP-1) receptor agonist are new therapeutic options for people with type 2 diabetes. Two FRCs-insulin degludec/liraglutide and insulin glargine/lixisenatide-have been approved for use in the United States. The two components in these FRCs target different aspects of diabetes pathophysiology, working in a complementary manner to decrease blood glucose while mitigating the side effects associated with each component (hypoglycemia and weight gain with insulin and gastrointestinal side effects with GLP-1 receptor agonists). This article reviews these products and key considerations for their use.

Insulin glargine/lixisenatide in type 2 diabetes: a profile of its use

“…Regardless of any potential differences between the available fixed-ratio basal insulin/GLP-1 RA combinations, meta-analyses indicate that regimens combining use of these agents provide robust glycaemic control [11,54], while mitigating the key drawbacks of insulins (i.e. bodyweight gain and hypoglycaemia) [11,54] and GLP-1 RAs (GI adverse events) [54]; this may improve adherence [55] and allow patients who are concerned about such issues (but require therapy intensification) to be more accepting of taking these agents [47]. However, initiating treatment early with fixedratio insulin glargine/lixisenatide may provide better efficacy and GI tolerability than using the agents sequentially, according to indirect comparative analyses of data from LixiLan-O and -L versus trials that assessed add-on lixisenatide in patients with uncontrolled T2D despite initiating or intensifying insulin glargine therapy (GetGoal Duo-1 and -2) [56]; direct comparisons are required to confirm these findings.…”

Translating iGlarLixi Evidence for the Management of Frequent Clinical Scenarios in Type 2 Diabetes

“…Due to its progressive nature, most people with T2D will eventually require treatment intensification with injectable therapies, specifically GLP-1 RAs and basal insulin [ 3 , 4 ]. FRCs consisting of both basal insulin and GLP-1 RA can address the unmet medical need for targeting both FPG and PPG in a simplified regimen [ 36 ]. Two such FRCs are approved by the Food and Drug Administration and European Medicines Agency for the treatment of T2D, iGlarLixi and IDegLira [ 10 – 13 ].…”

“…Residual hyperglycemia, defined as a HbA 1c above target despite FPG at or near target, is a pattern associated with failure to reach glycemic targets in 24–54% of individuals with T2D, indicating a need for postprandial glycemic control [ 35 ]. iGlarLixi combination therapy facilitates PPG control through the action of Lixi in slowing gastric emptying [ 8 ], and FPG control through stimulation of glucose-lowering activity by iGlar [ 36 ]. In participants with HbA 1c > 7% and FPG ≤ 130 mg/dL, iGlarLixi reduced the proportion of people with residual hyperglycemia more than iGlar alone after 30 weeks (24% of participants with residual hyperglycemia at week 30 with iGlarLixi vs. 47% with iGlar; p < 0.0001) [ 37 ].…”

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].…”