Effect of Liraglutide Treatment on Whole-body Glucose Fluxes in C-peptide-Positive Type 1 Diabetes During Hypoglycemia.

Abstract

The effect of liraglutide in C-peptide-positive (C-pos) type 1 diabetes (T1D) patients during hypoglycemia remains unclear. To investigate the effect of a 12-week liraglutide treatment on the body glucose fluxes during a hypoglycemic clamp in C-pos T1D patients and its impact on the alpha- and beta-cell responses during hypoglycemia. This was a randomized, double-blind, crossover 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 washout period. Fourteen T1D patients with fasting C-peptide ≥ 0.1 nmol/L. All patients underwent a hyperinsulinemic-stepwise-hypoglycemic 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. The responses of endogenous glucose production (EGP) and rate of peripheral glucose disposal (Rd) were similar for liraglutide and placebo treatment during the clamp. The numbers of hypoglycemic 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 hypoglycemia 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. Hemoglobin A1c and body weight were lower, and a trend for reduced insulin was seen after liraglutide treatment. The results indicate that 3 months of liraglutide treatment does not promote or prolong hypoglycemia in C-pos T1D patients.