THE ONCE-DAILY HUMAN GLP-1 ANALOG LIRAGLUTIDE SIGNIFICANTLY IMPROVES TOTAL CHOLESTEROL AND THE PREVALENCE OF METABOLIC SYNDROME IN TYPE 2 DIABETES: A META-ANALYSIS OF SIX CLINICAL TRIALS [P3-431]

Pratley RE, Toft AD, Falahati A, Plutzky J; University of Vermont Burlington, VT; Novo Nordisk A/S, Virum, Denmark; Brigham and Women’s Hospital, Boston, MA

The metabolic syndrome is a cluster of related risk factors that are associated with an increased likelihood of diabetes and cardiovascular disease, including dyslipidemia, elevated blood pressure, and elevated plasma glucose.¹

This study compared the effects of the glucagon-like peptide-1 analogue liraglutide with several other diabetes therapies on cholesterol values and the prevalence of the metabolic syndrome in patients with type 2 diabetes. The investigators performed a meta-analysis of data from 6 randomized, phase III clinical trials in which liraglutide 1.8 mg was compared with glimepiride, rosiglitazone, exenatide, insulin glargine, or placebo. The trials included a total combined population of 3967 patients. Statistical analyses focused on the differences between liraglutide and the other treatment groups; statistical analyses for the other possible between-treatment comparisons (eg, rosiglitazone v placebo or glimepiride) were not reported. After 26 weeks, mean total cholesterol values in patients who received insulin glargine or placebo increased by approximately 1 mg/dL from baseline, and patients who received rosiglitazone exhibited a mean increase of approximately 10 mg/dL. Patients who received liraglutide exhibited an average decrease of total cholesterol from baseline of approximately 5 mg/dL (P <.01 vs insulin glargine and placebo; P <.001 vs rosiglitazone). Mean decreases of approximately 2 to 3 mg/dL were noted for patients who received glimepiride or exenatide (not statistically different from placebo or liraglutide). For low-density lipoprotein (LDL) values, liraglutide-treated patients exhibited a mean decrease of approximately 7 mg/dL from baseline; rosiglitazone was associated with an increase of approximately 1 mg/dL (P <.001 vs liraglutide), and the other treatments resulted in decreases of approximately 2 to 5 mg/dL (P <.05 for liraglutide vs glimepiride and P <.01 for liraglutide vs insulin glargine). For high-density lipoprotein (HDL), all of the treatment groups except rosiglitazone exhibited small decreases from baseline, of approximately 1 mg/dL. In the rosiglitazone group, mean HDL increased slightly from baseline, by a mean of less than 1 mg/dL. The difference between the liraglutide and rosiglitazone groups was statistically significant (P <.001). Patients who were treated with liraglutide were significantly less likely than those who received placebo or glimepiride to meet diagnostic criteria for metabolic syndrome (odds ratio vs placebo, 0.6; P <.001; odds ratio vs glimepiride, 0.43; P <.001).

This analysis demonstrated that liraglutide significantly improved lipid parameters in comparison with placebo or other antidiabetic medications. The difference in lipid parameters was especially large between the liraglutide and rosiglitazone groups. Other recent studies have also suggested that rosiglitazone may worsen some lipid parameters. In one prospective study of 802 patients with type 2 diabetes and dyslipidemia, triglyceride levels decreased after 12 weeks for patients who were treated with pioglitazone, but increased among patients who received rosiglitazone.² Both groups exhibited increased LDL levels from baseline, but the increase was significantly greater for patients in the rosiglitazone group. It is not clear how these observations relate to the potential for cardiovascular disease in patients with diabetes, although a widely reported meta-analysis published in 2007 found that rosiglitazone was associated with a significantly increased risk of myocardial infarction or death from cardiovascular disease compared to patients not using rosiglitazone.³ However, the issue of whether rosiglitazone increased myocardial infarction or cardiovascular disease death remains controversial because several subsequent meta-analyses confirmed these findings,^4,5 while others did not.^6-8 As a result of this controversy, the labeling of rosiglitazone was modified in 2007 to include a black-box warning regarding an increased risk of congestive heart failure and myocardial ischemia.⁹

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