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.
Keywords: Glucagon-like peptide-1 analogue; Insulin therapy; Type 2 diabetes.