iGlarLixi Reduces Glycated Hemoglobin to a Greater Extent Than Basal Insulin Regardless of Levels at Screening: Post Hoc Analysis of LixiLan-L

Abstract

Introduction: The treatment of patients with type 2 diabetes uncontrolled on basal insulin and oral glucose-lowering drugs was investigated previously in the LixiLan-L trial. In the LixiLan-L trial, patients experienced a 6-week run-in with insulin glargine U100 (iGlar) as part of the screening phase, followed by treatment with a fixed-ratio combination of iGlar + lixisenatide (iGlarLixi) or iGlar alone over 30 weeks. In the study reported here, we investigated the achievement of glycemic control in those who completed the 30-week LixiLan-L trial, as assessed by change in glycated hemoglobin (HbA_1c) levels from screening, both for the overall category and for screening HbA_1c subcategories.

Methods: This post hoc analysis of the LixiLan-L trial included both the screening phase and the treatment period for 30-week completers and evaluated the change in HbA_1c from screening to Week 30, patients reaching HbA_1c < 7% at Week 30, and iGlar and lixisenatide (Lixi) doses at Week 30 overall and according to HbA_1c subcategory at screening (HbA_1c ≤ 8%, 8% < HbA_1c ≤ 9%, and HbA_1c > 9%). Documented symptomatic hypoglycemia during the treatment period was also assessed.

Results: HbA_1c reductions (least squares mean) from screening to Week 30 were greater for iGlarLixi than iGlar, both overall (- 1.7 vs. - 1.1%) and in all subgroups (HbA_1c ≤ 8%, 8% < HbA_1c ≤ 9%, and HbA_1c > 9%): - 1.1, - 1.4, - 2.4 (iGlarLixi) vs. - 0.5, - 1.0, - 1.8% (iGlar), respectively (all p < 0.0001). The end-of-treatment mean HbA_1c level for iGlarLixi across all groups was < 7%. More patients achieved an HbA_1c of < 7% with iGlarLixi than with iGlar, both overall (59.9 vs. 31.2%) and within each subgroup [74.2, 54.7, 52.2 (iGlarLixi) vs. 37.2, 31.6, 23.5% (iGlar), respectively]. A higher initial screening HbA_1c corresponded with a greater mean reduction in HbA_1c for both treatment strategies. In all HbA_1c screening categories, the risk of hypoglycemia was not increased with iGlarLixi versus iGlar during the treatment phase.

Conclusion: iGlarLixi controlled HbA_1c levels more effectively than iGlar across all HbA_1c screening subgroups and in the overall study population without increasing the risk of hypoglycemia.

Trial registration: Clinicaltrials.gov Identifier: NCT02058160.

Funding: Sanofi.

Keywords: Glycated hemoglobin; Insulin glargine U100; Lixisenatide; Type 2 diabetes; iGlarLixi.