• Hyperglycemia/Hypoglycemia
• Diabetes & Endocrinology Clinical Trials
• Diabetes Mellitus

Urd Kielgast, MD, The Panum Institute and Hvidovre University Hospital, Copenhagen, Denmark, reported results from a 4-week randomized, open-label efficacy trial on the effects of treatment with liraglutide, a once-daily human GLP-1 receptor analog, on insulin dose and glycemic control in patients with type 1 diabetes mellitus (T1DM) with and without residual β-cell function [NCT00993720; Kielgast U et al. Diabetes Care 2011]. Findings suggest that treatment with liraglutide reduced insulin dose with improved or unaltered glycemic control.

Ten T1DM patients with residual β-cell function (C-peptide-positive) and 19 without (C-peptide-negative) participated in the study. C-peptide-positive patients were treated with liraglutide plus insulin for 4 weeks; C-peptide-negative patients were randomly assigned to either 4 weeks of liraglutide plus insulin or insulin alone (control subjects). The primary outcome was insulin dose over the 4-week study period.

Patients were recruited through outpatient clinics. Inclusion criteria were age 18 to 50 years, body mass index 18 to 27 kg/m², Caucasian descent, diabetes diagnosis between the ages of 5 and 40 years, no known cardiovascular diseases or diabetes complications (except microalbuminuria), remission period that was assumed to have ended, no use of medication that was known to affect glucose metabolism, and symptoms of autonomic neuropathy. Participants were excluded if screening revealed previously unrecognized late diabetes complications, autonomic neuropathy, anemia, or HbA1C >8.5%.

In Week 0, glycemic control was evaluated through frequent blood glucose measurements, and insulin dose was corrected to ensure the best possible glycemic control before entering the study. Before liraglutide was started, fast-acting insulin was decreased by 50% and long-acting insulin by 0% to 20%. During the next 3 days and again in Week 2, patients received telephone follow-ups, and their insulin dose was titrated up or down to meet predefined criteria for glucose control (premeal 5 to 7 mM), based on daily glucose profiles of no less than 7 points.

Between Weeks 0 and 4, insulin dose (U/kg/day) in C-peptide-positive patients who were taking liraglutide fell from 0.50±0.06 to 0.31±0.8 (p<0.001) and from 0.72±0.08 to 0.59±0.06 (p=0.01) in C-peptide-negative patients. In C-peptide-negative patients who were taking insulin, there was no significant difference between doses at Week 0 (0.62±0.04) and Week 4 (0.64±0.05; p=NS).

In both groups of liraglutide-treated patients, HbA1C decreased between Weeks 0 and 4 from 6.6±0.23 to 6.4±0.3 (p=0.03) in C-peptide-positive patients and from 7.5±0.40 to 7.0±0.1 (p=0.01) in C-peptide-negative patients. In the control group, the change was not significant (7.1±0.1 vs 6.9±0.2). Between Weeks 0 and 4, there was no change in β-cell function in C-peptide-positive T1DM patients (n=8; 520±11 pmol/L vs 457±79 pmol/L; p=0.4).

Four weeks' treatment with liraglutide significantly reduced insulin dose with improved or unchanged glycemic control in T1DM patients with and without residual β-cell function. The decrease was accompanied by a tendency toward reduced hypoglycemia. The treatment effect was larger in patients with residual β-cell function, some of whom discontinued insulin treatment. Almost all patients who were treated with liraglutide lost weight but also had gastrointestinal side effects. These side effects may limit the usefulness of GLP-1-based therapies in some patients.

• © 2011 MD Conference Express®