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

Abstract

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

Objective: 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.

Design: 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.

Setting and participants: Fourteen T1D patients with fasting C-peptide ≥ 0.1 nmol/L.

Intervention(s): 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.

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 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.

Conclusions: The results indicate that 3 months of liraglutide treatment does not promote or prolong hypoglycemia in C-pos T1D patients.

Trial registration: ClinicalTrials.gov NCT02408705.

Keywords: GLP-1 analogue; beta-cell function; clinical trial; hypoglycemia; liraglutide; type 1 diabetes.