Benefits of the fixed‐ratio combination of insulin glargine 100 units/mL and lixisenatide (iGlarLixi) in Japanese people with type 2 diabetes: A subgroup and time‐to‐control analysis of the LixiLan JP phase 3 trials

Abstract

Aims To explore the impact of baseline characteristics on clinical outcomes in the phase 3 LixiLan JP trials which evaluated the efficacy and safety of iGlarLixi, a titratable fixed‐ratio combination of insulin glargine 100 units/mL (iGlar) and GLP‐1 RA lixisenatide (Lixi), vs Lixi (JP‐O1, NCT02749890) or iGlar (LixiLan JP‐O2, NCT02752828; JP‐L, NCT02752412) in Japanese people with type 2 diabetes uncontrolled on oral antidiabetes drugs (OADs; JP‐O1, JP‐O2) or OADs and basal insulin (JP‐L). Materials and methods Glycated haemoglobin (HbA1c) change from baseline to week 26 was assessed within patient subgroups. Subgroups were defined by dipeptidyl peptidase‐4 inhibitor use at screening (JP‐O1, JP‐O2 only), baseline HbA1c (<8%, ≥8%), baseline BMI (<25, ≥25 kg/m2) and age (<65, ≥65 years). Incidences of hypoglycaemia (baseline HbA1c, BMI and age subgroups) and gastrointestinal disorders (age subgroup) were evaluated over 52 (JP‐O1) or 26 weeks (JP‐O2, JP‐L). Time to control (first HbA1c <7% or fasting plasma glucose [FPG] ≤130 mg/dL; JP‐O2 only) was also assessed. Results HbA1c reductions were consistently greater with iGlarLixi vs iGlar or Lixi across all subgroups, and iGlarLixi was equally effective in all subgroups. Incidences of documented symptomatic hypoglycaemia (plasma glucose ≤3.9 mmol/L) were higher with iGlarLixi vs Lixi and generally comparable with iGlar. Across age subgroups, incidences of gastrointestinal disorders with iGlarLixi were higher vs iGlar, but lower vs Lixi. Median time to HbA1c or FPG control was shorter with iGlarLixi vs iGlar. Conclusions iGlarLixi was consistently effective across all baseline characteristic subgroups, with more patients achieving glycaemic control vs iGlar early in treatment.

Effects of age and disease duration on the efficacy and safety of iGlarLixi in Asian people with type 2 diabetes: A post hoc analysis of the LixiLan‐O‐AP and LixiLan‐L‐CN trials

“…In these previous analyses, iGlarLixi was associated with significantly greater HbA1c reductions compared with iGlar or Lixi among participants in both age subgroups (<65 and ≥65 years) 33,34 . Similar to the current analysis, regardless of age, the incidence of documented symptomatic hypoglycaemia with iGlarLixi was generally similar to that with iGlar and the incidence of gastrointestinal AEs was lower with iGlarLixi versus Lixi 33,34 . In addition to the findings of the current post hoc analysis, iGlarLixi had non‐inferior glycaemic efficacy and superior efficacy with regard to weight change to that of premixed 30% insulin aspart plus 70% insulin aspart protamine (BIAsp 30) in the global SoliMix study in people with uncontrolled T2D on BI plus OAD therapy, including participants aged ≥65 years and those with T2D for ≥10 years 35 …”

“…33,34 Similar to the current analysis, regardless of age, the incidence of documented symptomatic hypoglycaemia with iGlarLixi was generally similar to that with iGlar and the incidence of gastrointestinal AEs was lower with iGlarLixi versus Lixi. 33,34 In addition to the findings of the current post hoc analysis, iGlarLixi had non-inferior glycaemic efficacy and superior efficacy with regard to weight change to that of premixed 30% insulin aspart plus 70% insulin aspart protamine (BIAsp 30) in the global SoliMix study in people with uncontrolled T2D on BI plus OAD therapy, including participants aged ≥65 years and those with T2D for ≥10 years. 35 The limitations of the current analysis include its post hoc nature, which means that this analysis is not powered to evaluate the primary endpoint, in particular in those subgroups with a low number of participants.…”

“…LixiLan JP-O1, LixiLan JP-O2 and LixiLan JP-L studies. 34 In these previous analyses, iGlarLixi was associated with significantly greater HbA1c reductions compared with iGlar or Lixi among participants in both age subgroups (<65 and ≥65 years). 33,34 Similar to the current analysis, regardless of age, the incidence of documented symptomatic hypoglycaemia with iGlarLixi was generally similar to that with iGlar and the incidence of gastrointestinal AEs was lower with iGlarLixi versus Lixi.…”

Lixisenatide is effective and safe as add-on treatment to basal insulin in Asian individuals with type 2 diabetes and different body mass indices: a pooled analysis of data from the GetGoal Studies

“…39 The current study demonstrates that lixisenatide as add-on therapy to basal insulin is effective in an Asian population, irrespective of BMI, and confirms previous data that lixisenatide efficacy is independent of BMI from studies in Caucasian or Japanese individuals with diabetes. [40][41][42] The results of this analysis are in line with other analyses conducted in individuals receiving other GLP-1 receptor agonists. Studies of both liraglutide 43 44 and exenatide [45][46][47][48][49] indicate that baseline BMI values are not predictive of the reduction in HbA1c seen with these treatments.…”

Use of iGlarLixi for the Management of Type 2 Diabetes in Japanese Clinical Practice: Prior Treatment Subgroup Analysis of the SPARTA Japan Study

“…As a result of a lack of clinically significant benefits, combining a DPP-4i and GLP-1 RA is not recommended [15], and typically DPP-4is are discontinued before initiating a GLP-1 RA or fixed-ratio combination containing a GLP-1 RA component. In this study, the analysis of the prior DPP-4i exposure on outcomes was conducted to confirm that switching from a DPP-4i to iGlarLixi does not lead to a deterioration in glycaemic control in clinical practice, and to confirm prior clinical trial data [16]. This analysis showed that prior DPP-4i use did not affect the HbA1c-lowering effect of iGlarLixi, did not negatively affect body weight during iGlarLixi treatment, and did not appear to impact changes in the iGlarLixi dose.…”