Efficacy and safety of insulin glargine/lixisenatide fixed‐ratio combination (iGlarLixi 1:1) in Japanese patients with type 2 diabetes mellitus inadequately controlled on oral antidiabetic drugs: A randomized, 26‐week, open‐label, multicentre study: The LixiLan JP‐O2 randomized clinical trial

Abstract

Aims To assess efficacy and safety of 26‐week treatment with insulin glargine/lixisenatide fixed‐ratio combination (iGlarLixi) compared with insulin glargine U100 (iGlar) in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OADs). Materials and Methods This phase 3, multicentre, open‐label, 1:1 randomized, parallel‐group study compared efficacy of iGlarLixi and iGlar in patients with T2DM, HbA1c of ≥7.5% to ≤9.5% and fasting plasma glucose ≤10.0 mmol/L (180 mg/dL). The primary endpoint was change in HbA1c from baseline to week 26. Results Patients were randomized to iGlarLixi (n = 260) or iGlar (n = 261) (mean age 59.7 years, baseline BMI 26.04 kg/m2, and HbA1c 8.04% [64.4 mmol/mol]). HbA1c reduction was significantly greater with iGlarLixi (−1.40% [−15.3 mmol/mol]) than with iGlar (−0.76% [−8.3 mmol/mol]). Significantly more iGlarLixi patients reached HbA1c <7% at week 26 (71.5% vs 38.5%, P < .0001), with significantly lower weight gain (LS mean difference −1.06 kg, P < .0001). Documented symptomatic hypoglycemia (plasma glucose ≤3.9 mmol/L [70 mg/dL]) was recorded in 14.2% of patients with iGlarLixi and 12.3% with iGlar. No severe hypoglycemia was reported in either group. Other than the expected gastrointestinal issues associated with glucagon‐like peptide 1 receptor agonists, we found no major difference in the incidence of TEAEs. Conclusions HbA1c reduction was significantly greater with iGlarLixi than with iGlar; significantly more patients achieved HbA1c <7%, with no additional risk of hypoglycemia and without weight gain. iGlarLixi (1:1) provided an effective treatment option for Japanese patients with T2DM inadequately controlled on OADs. Clinical Trial Number: NCT02752828

Fixed‐ratio combination of basal insulin and glucagon‐like peptide‐1 receptor agonists in the treatment of Japanese people with type 2 diabetes: An innovative solution to a complex therapeutic challenge

“…Mean baseline HbA1c levels for each study population were 8.4% (JP‐O1), 8.0% (JP‐O2) and 8.3% (JP‐L) 65–67 . Least squares (LS) mean HbA1c reductions were −1.58% (iGlarLixi) versus −0.51% (Lixi) in JP‐O1, −1.40% (iGlarLixi) versus −0.76% (iGlar) in JP‐O2 66,67 and −1.27% (iGlarLixi) versus −0.53% (iGlar) in JP‐L 65 . Furthermore, significantly greater proportions of participants achieved HbA1c <53 mmol/mol (<7%) with iGlarLixi (65.2% in JP‐O1; 71.5% in JP‐O2; 51.8% in JP‐L) versus Lixi (19.4% in JP‐O1) or iGlar (38.5% in JP‐O2; 16.0% in JP‐L; P < 0.0001 for all studies) 65–67 .…”

“…Three phase 3 studies of iGlarLixi have been conducted in Japan [LixiLan JP‐O1 (NCT02749890), 66 ‐O2 (NCT02752828) 67 and ‐L (NCT02752412)] 65 . All three trials were open‐label, randomized, active‐controlled, parallel‐group, multicentre studies evaluating the efficacy and safety of iGlarLixi versus Lixi or iGlar (Table 1).…”

“…All three trials were open‐label, randomized, active‐controlled, parallel‐group, multicentre studies evaluating the efficacy and safety of iGlarLixi versus Lixi or iGlar (Table 1). LixiLan JP‐O1 and ‐O2 evaluated iGlarLixi in people with T2D inadequately controlled on one or two OADs (vs. Lixi in JP‐O1 and iGlar in JP‐O2) 65–67 . LixiLan JP‐L evaluated iGlarLixi versus iGlar in people with T2D inadequately controlled on BI (<15 U) and one or two OADs; this study also included a 12‐week run‐in period before randomization, during which study participants switched to or continued on iGlar treatment with dose titration to maintain acceptable glycaemic control, and continued or initiated metformin as mandatory background therapy and discontinued all other previously taken OADs.…”

“…The three studies met their primary endpoint of significantly greater reduction in HbA1c from baseline to week 26 with iGlarLixi versus comparator [Lixi or iGlar; P < 0.0001 for all (Table 2)] 65–67 . Mean baseline HbA1c levels for each study population were 8.4% (JP‐O1), 8.0% (JP‐O2) and 8.3% (JP‐L) 65–67 .…”

“…The three studies met their primary endpoint of significantly greater reduction in HbA1c from baseline to week 26 with iGlarLixi versus comparator [Lixi or iGlar; P < 0.0001 for all (Table 2)] 65–67 . Mean baseline HbA1c levels for each study population were 8.4% (JP‐O1), 8.0% (JP‐O2) and 8.3% (JP‐L) 65–67 . Least squares (LS) mean HbA1c reductions were −1.58% (iGlarLixi) versus −0.51% (Lixi) in JP‐O1, −1.40% (iGlarLixi) versus −0.76% (iGlar) in JP‐O2 66,67 and −1.27% (iGlarLixi) versus −0.53% (iGlar) in JP‐L 65 .…”