Fixed-Ratio Combination of Insulin and GLP-1 RA in Patients with Longstanding Type 2 Diabetes: A Subanalysis of LixiLan-L

INTRODUCTION: With longer duration and progression of type 2 diabetes (T2D), β-cell function deteriorates and insulin therapy often becomes necessary. Glucagon-like peptide-1 receptor agonists such as lixisenatide that do not rely only on β-cell function and glucagon suppression primarily, but also lower glucose by other (insulin-independent) mechanisms such as delayed gastric emptying, may be appropriate adjuvant therapy to basal insulin in patients with longstanding T2D. METHODS: We assessed the efficacy and safety of insulin glargine (iGlar) versus iGlarLixi, a fixed-ratio combination of iGlar and lixisenatide, stratified by quartiles (Q) of T2D duration (≤ 7.305 [Q1], > 7.305 to ≤ 10.75 [Q2], > 10.75 to ≤ 15.67 [Q3], and > 15.67 years [Q4]) in the LixiLan-L trial (N = 736). RESULTS: Across all quartiles, the reduction in glycated haemoglobin was greater with iGlarLixi versus iGlar, and the difference was most pronounced in patients with the longest duration (Q4; least squares mean difference [standard error] − 0.62 [0.13], P < 0.0001). Additionally, hypoglycaemia rates were significantly lower with iGlarLixi versus iGlar in patients in Q4 (3.3 vs. 6.9 events/patient-year, P < 0.0001). CONCLUSION: iGlarLixi lowered glycated haemoglobin more versus iGlar regardless of T2D duration, with benefit retained even among patients with the longest T2D duration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-020-00797-y) contains supplementary material, which is available to authorized users.