BARCELONA — Liraglutide, a once-daily investigational human glucagon-like peptide-1 analogue, achieved impressive reductions in multiple cardiovascular risk biomarkers in type 2 diabetes patients in a meta-analysis of six phase III randomized trials.
The trials, which collectively included 3,967 patients with type 2 diabetes followed for 6 months, variously compared liraglutide with rosiglitazone, glimepiride, exenatide, insulin glargine, and placebo.
Liraglutide reduced hyperlipidemia to a significantly greater extent than any of the other antidiabetic medications. The same was true for plasma brain natriuretic peptide (BNP), a marker of cardiovascular risk; indeed, liraglutide was the sole agent to significantly reduce BNP. And liraglutide was second only to rosiglitazone in its magnitude of C-reactive protein reduction, Dr. Alan Garber reported at the annual congress of the European Society of Cardiology.
Rosiglitazone produced an unwelcome mean 31% increase in BNP compared with baseline, in contrast to the 12% decrease with liraglutide. And while liraglutide resulted in a significant mean 5 mg/dL reduction in total cholesterol, rosiglitazone-treated patients had an 11 mg/dL increase, noted Dr. Garber, professor of medicine, biochemistry, and molecular biology at Baylor College of Medicine, Houston.
Neither glimepiride, exenatide, insulin glargine, nor placebo resulted in significant changes over time in BNP or total cholesterol, the endocrinologist added.
Liraglutide was the only agent to significantly reduce triglycerides, achieving a mean 7.7 mg/dL reduction. The mean LDL decrease of 7.7 mg/dL seen with liraglutide was significantly more robust than that of other therapies, as was the 3.5 mg/dL decrease in free fatty acids achieved with the glucagon-like peptide-1 analogue. The mean reduction in C-reactive protein with liraglutide was 23%, while rosiglitazone achieved a 43% reduction.
In the six phase III trials, liraglutide reduced mean hemoglobin A1c values by 1.0%-1.5%, systolic blood pressure by 2–6 mm Hg, and body weight by a mean of 1.8 kg. Exenatide reduced body weight by 1.3 kg, while insulin glargine and glimepiride resulted in significant gains of 1.6 and 2.1 kg, respectively.
Some of the benefits of liraglutide can be attributed to the weight loss; however, there is also evidence to indicate an additional direct beneficial effect of the agent itself independent of weight loss, according to Dr. Garber.
Liraglutide has received marketing approval in Europe and is now undergoing Food and Drug Administration review for possible marketing approval as an adjunct to diet and exercise and in combination therapy with oral antidiabetic drugs to improve glycemic control in patients who have type 2 diabetes.
Novo Nordisk has provided the FDA with an estimate that liraglutide reduces the risks of fatal and nonfatal myocardial infarction and stroke by at least 20% on the basis of the clinical investigators' reported observations.
Dr. Garber disclosed that he is on the speakers bureaus and advisory boards for Novo Nordisk, GlaxoSmithKline, Merck, and Roche.
Liraglutide was the only agent to significantly reduce triglycerides, with a mean 7.7 mg/dL reduction.
Source DR. GARBER