Effect of Liraglutide Treatment on Whole Body Glucose Fluxes in C-peptide Positive Type 1 Diabetes During Hypoglycaemia

Context

The effect of liraglutide in C-peptide positive (C-pos) type 1 diabetes (T1D) patients during hypoglycaemia remains unclear.

Objective

To investigate the effect of a 12-week liraglutide-treatment on the body glucose fluxes during a hypoglycaemic clamp in C-pos T1D patients and its impact on the alpha and beta cell responses during hypoglycaemia.

Design

This was a randomized, double-blind, cross-over study. Each C-pos T1D patient was allocated to the treatment-sequence liraglutide/placebo or placebo/liraglutide with daily injections for 12 weeks adjunct to insulin-treatment, separated by a 4-week wash-out period.

Setting and Participants

14 T1D patients with fasting C-peptide ≥ 0.1 nmol/l.

Intervention(s)

All patients underwent a hyperinsulinaemic-stepwise-hypoglycaemic clamp with isotope tracer [plasma glucose (PG)-plateaus: 5.5, 3.5, 2.5 and 3.9 mmol/l] after a 3-month-liraglutide- (1.2 mg) or placebo-treatment.

Main Outcome Measure(s)

The responses of endogenous glucose production (EGP) and rate of peripheral glucose disposal (Rd) were similar for liraglutide- and placebo-treatment during the clamp.

Results

The numbers of hypoglycaemic events were similar in both groups. At the clamp, mean glucagon levels were significantly lower at PG-plateau 5.5 mmol/l in the liraglutide- than in the placebo-group, but showed similar responses to hypoglycaemia in both groups. Mean C-peptide levels were significantly higher at PG-plateaus 5.5 and 3.5 mmol/l after liraglutide-treatment, but this effect was not reflected in EGP and Rd. HbA1c and body weight were lower and a trend for reduced insulin was seen after liraglutide-treatment.

Conclusions

The results indicate that three months liraglutide-treatment does not promote or prolong hypoglycaemia in C-pos T1D patients.