1. Liraglutide and the Preservation of Pancreatic β-Cell Function in Early Type 2 Diabetes: The LIBRA Trial
Featured Article:
Ravi Retnakaran, Caroline K. Kramer, Haysook Choi, Balakumar Swaminathan, and Bernard Zinman
Diabetes Care
Volume 37:
December, 2014

2. STUDY OBJECTIVE
Study determined whether liraglutide can preserve -cell function over 48 weeks in early type 2 diabetes (T2DM) after initial elimination of glucotoxicity with intensive insulin therapy (IIT)
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3. STUDY DESIGN AND METHODS
Study was a double-blind, randomized, placebo-controlled trial with 51 patients with T2DM of 2.6 ± 1.9 years’ duration and an A1C of 6.8 ± 0.8%
Subjects completed 4 weeks of IIT before randomization to daily subcutaneous liraglutide or placebo injection
Serial assessment of -cell function was performed with an Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral glucose tolerance test every 12 weeks
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4. Data are %; mean 6 SD, if normally distributed; or median (25th–75th), if skewed.
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5. Data are mean 6 SE or %. P for linear trend
Data are mean 6 SE or %. *P for linear trend. §Data are geometric mean (95% CI).
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6. RESULTS
Primary outcome of baseline-adjusted ISSI-2 at 48 weeks was higher in the liraglutide group than in the placebo group
Baseline-adjusted HbA1c at 48 weeks was lower in the liraglutide group
At each quarterly assessment, >50% of participants on liraglutide had an HbA1c ≤6.0% and glucose tolerance in the nondiabetic range
No difference was found in the incidence of hypoglycemia between the liraglutide and placebo groups
Two weeks after stopping treatment, the beneficial effect on ISSI-2 of liraglutide versus placebo was entirely lost
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7. Figure 1—Changes over time in b-cell function, measured by ISSI-2 (A), DIns0–120/Dgluc01203Matsuda index (B); DCpep0–120/Dgluc0–1203Matsuda index (C); and DISR0–120/Dgluc0–120 3 Matsuda index (D). P values are for interaction between treatment group and time during the intervention. Due to single negative or missing values precluding use of the index, the respective sample sizes analyzed in the placebo and liraglutide groups in B–D were as follows: 24 and 21 for DIns0–120/Dgluc0–120 3 Matsuda index; 24 and 23 for DCpep0–120/Dgluc0–120 3 Matsuda index; and 24 and 23 for DISR0–120/Dgluc0–120 3 Matsuda index. Pre-IIT, before IIT; Rand, randomization visit.
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8. Figure 2—Changes over time in HbA1c (A), Matsuda index of insulin sensitivity (B), BMI (C), and waist circumference (D). P values are for interaction between treatment group and time during the intervention. Pre-IIT, before IIT; Rand, randomization visit.
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9. CONCLUSIONS
Liraglutide provides robust enhancement of -cell function that is sustained over 48 weeks in early T2DM but lost on cessation of therapy
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10. Figure 3—Proportion of participants in each treatment group with HbA1c,6.5% (,48 mmol/mol) (A), HbA1c #6.0% (#42 mmol/mol) (B), and glucose tolerance status in the nondiabetic range on OGTT (C). *P , 0.05 for comparison between groups. Rand, randomization visit.
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