November - 4 - 2009
Several meta-analyses of large clinical trials of liraglutide in patients with type 2 diabetes were presented at the recent World Diabetes Congress and are summarized here. The agent was approved in the European Union this year and is preregistered in the U.S.
During 6 randomized, controlled, phase 3 Liraglutide Effect and Action in Diabetes (LEAD) trials, 1,683 patients maintained their pretrial regimen of oral antidiabetic drugs, and those adding liraglutide 1.8 and 1.2 mg had significant mean reductions in HbA1c from baseline (1.5 and 1.3%, respectively). These liraglutide doses were also associated with reductions in fasting plasma glucose (FPG), weight and systolic blood pressure (Pratley, R. et al. 20th World Diabet Congr (Oct 18-22, Montreal) 2009, Abst P-1401).
A meta-analysis of the 6 trials found that liraglutide 1.8 and 1.2 mg significantly reduced HbA1c across quartiles of HOMA-B and C-peptide, with the greatest improvements in HbA1c observed in patients with the most preserved beta-cell function (Matthews, D. et al. 20th World Diabet Congr (Oct 18-22, Montreal) 2009, Abst P-1399).
Treatment with liraglutide 1.8 mg for 26 weeks resulted in changes from baseline in HbA1c compared with placebo in patients with different levels of weight change from baseline, according to an analysis of 2,739 patients included in the 6 trials. This indicates that treatment benefit is not dependent on the amount of weight loss (Schmidt, W.E. et al. 20th World Diabet Congr (Oct 18-22, Montreal) 2009, Abst P-1398).
Another analysis of LEAD trial data found that reductions in HbA1c from baseline with liraglutide 1.8 mg were similar in patients aged 65 years or under and in those over 65 years of age (1.39% vs. 1.32%). Body weight change and tolerability were also similar between these age groups (Bode, B. et al. 20th World Diabet Congr (Oct 18-22, Montreal) 2009, Abst P-1353).
Analysis of the 6 LEAD trials also showed that the odds ratio for reaching HbA1c < 7.0% was significantly greater for liraglutide 1.8 mg vs. all comparator treatments (rosiglitazone, glimepiride, insulin glargine, exenatide, placebo) and the odds ratio was significantly greater for achieving HbA1c with liraglutide 1.2 mg compared to rosiglitazone, glimepiride and placebo (Zinman, B. et al. 20th World Diabet Congr (Oct 18-22, Montreal) 2009, Abst D-0910).
One last LEAD program meta-analysis showed that liraglutide 1.2 and 1.8 mg significantly reduced systolic blood pressure from baseline compared with placebo (2.5, 2.6 and 0.2 mmHg, respectively). Liraglutide was found to reduce systolic blood pressure within 2 weeks and the effect was maintained over 26 weeks with the greatest reductions seen in patients with baseline hypertension (Fonseca, V. et al. 20th World Diabet Congr (Oct 18-22, Montreal) 2009, Abst D-0908).
Finally, two phase III liraglutide trials have been conducted in Japanese patients. In one trial, liraglutide 0.9 mg was associated with a greater reduction in HbA1c from baseline than glibenclamide at 1 year (-1.48 vs. -0.95%). In the other trial, the combination of sulfonylurea with liraglutide 0.6 or 0.9 mg reduced HbA1c more after 1 year (-1.09 and -1.30%, respectively) compared with sulfonylurea alone (-0.06%) (Seino, Y. et al. 20th World Diabet Congr (Oct 18-22, Montreal) 2009, Abst D-0912).