Lixisenatide in type 1 diabetes: A randomised control trial of the effect of lixisenatide on post-meal glucose excursions and glucagon in type 1 diabetes patients

Abstract

Aims: The GLP1 agonist lixisenatide is glucagonostatic and reduces post-prandial blood glucose (PPBG) in type 2 diabetes. This study investigates its impact in type 1 diabetes (T1D). Methods: In a blinded, crossover trial, 25 patients with T1D were randomised to 4 weeks adjunctive treatment with lixisenatide (L) or placebo (P), with a 4-week washout period. The primary outcome was percentage of 3 hours PPBG in target (4-10 mmol/L) assessed by CGM before and after treatment. Participants also underwent post-treatment standardised mixed meal test (MMT, n = 25) and hyperinsulinaemic hypoglycaemic clamp (n = 15). Results: PPBG CGM readings in target were similar between L vs P (Mean % ± SE, breakfast 45.4 ± 6.0 vs 44.3 ± 6.0, P =.48, lunch 45.5 ± 5.8 vs 50.6 ± 5.3, P =.27 and dinner 43.0 ± 6.7 vs 47.7 ± 5.6, P =.30). HbA1C was similar between L vs P (64.7 ± 1.6 vs 64.1 ± 1.6 mmol/mol, P =.30). Prandial insulin fell after lixisenatide (dose change −0.7 ± 0.6 vs +2.4 ± 0.7 units/d, P =.004), but basal insulin dose was similar between groups. The post-MMT glucose area under the curve (AUC) was lower with L than P (392.0 ± 167.7 vs 628.1 ± 132.5 mmol/L × min, P