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

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. 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). 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). iGlarLixi lowered glycated haemoglobin more versus iGlar regardless of T2D duration, with benefit retained even among patients with the longest T2D duration.