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.

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,  = .48, lunch 45.5 ± 5.8 vs 50.6 ± 5.3,  = .27 and dinner 43.0 ± 6.7 vs 47.7 ± 5.6,  = .30). HbA1C was similar between L vs P (64.7 ± 1.6 vs 64.1 ± 1.6 mmol/mol,  = .30). Prandial insulin fell after lixisenatide (dose change -0.7 ± 0.6 vs +2.4 ± 0.7 units/d,  = .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,  < .001), as was the corresponding glucagon AUC (140.0 ± 110.0 vs 304.2 ± 148.2 nmol/L × min,  < .001). Glucagon and counter-regulatory hormone values at a blood glucose of 2.4 mmol/L during the hypoglycaemic clamp were similar between L and P.

Conclusion: In T1D, PPBG values were not altered by adjunctive lixisenatide although prandial insulin dose fell. Glucose and glucagon level during an MMT were significantly lower after lixisenatide, without affecting counter-regulatory response during hypoglycaemia.