Liraglutide and the preservation of pancreatic β-cell function in early type 2 diabetes: the LIBRA trial.

Abstract

OBJECTIVE:

Clinical studies evaluating the effects of medications on β-cell function in type 2 diabetes (T2DM) are compromised by an inability to determine the actual baseline degree of β-cell dysfunction independent of the reversible dysfunction induced by hyperglycemia (glucotoxicity). Short-term intensive insulin therapy (IIT) is a strategy for eliminating glucotoxicity before randomization. This study determined whether liraglutide can preserve β-cell function over 48 weeks in early T2DM following initial elimination of glucotoxicity with IIT.

RESEARCH DESIGN AND METHODS:

In this double-blind, randomized, placebo-controlled trial, 51 patients with T2DM of 2.6 ± 1.9 years' duration and an A1C of 6.8 ± 0.8% (51 ± 8.7 mmol/mol) completed 4 weeks of IIT before randomization to daily subcutaneous liraglutide or placebo injection, with serial assessment of β-cell function by Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral glucose tolerance test performed every 12 weeks.

RESULTS:

The primary outcome of baseline-adjusted ISSI-2 at 48 weeks was higher in the liraglutide group than in the placebo group (339.8 ± 27.8 vs. 229.3 ± 28.4, P = 0.008). Baseline-adjusted HbA1c at 48 weeks was lower in the liraglutide group (6.2 ± 0.1% vs. 6.6 ± 0.1%, P = 0.055) (44 ± 1.1 vs. 49 ± 1.1 mmol/mol). At each quarterly assessment, >50% of participants on liraglutide had an HbA1c ≤6.0% (42 mmol/mol) and glucose tolerance in the nondiabetic range. Despite this level of glycemic control, no difference was found in the incidence of hypoglycemia between the liraglutide and placebo groups (P = 0.61). Two weeks after stopping treatment, however, the beneficial effect on ISSI-2 of liraglutide versus placebo was entirely lost (191.9 ± 24.7 vs. 238.1 ± 25.2, P = 0.20).

CONCLUSIONS:

Liraglutide provides robust enhancement of β-cell function that is sustained over 48 weeks in early T2DM but lost upon cessation of therapy.

• Authors: Ravi Retnakaran, Caroline K Kramer, Haysook Choi, Balakumar Swaminathan, Bernard Zinman
• Journal: Diabetes care (Diabetes Care) Vol. 37 Issue 12 Pg. 3270-8 (Dec 2014) ISSN: 1935-5548 [Electronic] United States
• PMID: 25249651 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Liraglutide
• Glucagon-Like Peptide 1

Topics

• Adult
• Aged
• Blood Glucose (drug effects, physiology)
• Cytoprotection
• Diabetes Mellitus, Type 2 (blood, drug therapy, physiopathology)
• Disease Progression
• Double-Blind Method
• Female
• Glucagon-Like Peptide 1 (analogs & derivatives, therapeutic use)
• Humans
• Hypoglycemia (epidemiology)
• Hypoglycemic Agents (therapeutic use)
• Insulin (therapeutic use)
• Insulin Resistance
• Insulin-Secreting Cells (drug effects, physiology)
• Liraglutide
• Male
• Middle Aged