Diabetes, obesity & metabolism

Liraglutide as adjunct to insulin treatment in type 1 diabetes does not interfere with glycaemic recovery or gastric emptying rate during hypoglycaemia: A randomized, placebo-controlled, double-blind, parallel-group study.

PMID 27868372


Glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy is a potential treatment as adjunct to insulin in type 1 diabetes (T1D). However, GLP-1RAs inhibit glucagon secretion and delay the gastric emptying (GE) rate and may impair recovery from hypoglycaemia. We evaluated the effect of the GLP-1RA liraglutide on counterregulatory responses and GE rate during hypoglycaemia in persons with T1D. In a 12-week, randomized, double-blind, placebo-controlled study, 20 patients aged >18 years with T1D and HbA1c ≥8% (64 mmol/mol) were randomly assigned (1:1) to liraglutide 1.2 mg once daily or placebo as add-on to insulin treatment. Before and at end of treatment a hypoglycaemic clamp (plasma glucose target 2.5 mmol/L) was carried out, followed by a liquid meal. Primary endpoint was change in GE rate (evaluated by area under the paracetamol curve and time to peak). Secondary endpoints included changes in glycaemic recovery, counter-regulatory hormones, pancreatic polypeptide (PP), GLP-1, blood pressure and heart rate. During the period June 2013 to October 2014, 20 patients were enrolled. After 12 weeks of treatment, changes in GE rates did not differ significantly between groups ( P  = .96), with no significant changes from baseline, whether evaluated from AUCs or time to peak. The secondary endpoints, glycaemic recovery, counter-regulatory hormone responses, systolic blood pressure and GLP-1 and PP responses, were also similar. Heart rate increased with liraglutide from 69 ± 4 to 80 ± 5 beats/min ( P  = .02). Liraglutide does not compromise glycaemic recovery, GE rate or counter-regulatory hormone responses in T1D patients during hypoglycaemia. No treatment-related safety issues were identified.