Glucagon-like peptide-1 mimetics improve certain cardiovascular risk factors, although it is unclear if the observed benefits are direct effects or indirect effects due to weight loss.
Improvements in systolic blood pressure seen in exenatide and liraglutide trials are illustrated in Figure 3. The decreases in systolic blood pressure range from 2.3 to 5.6 mm Hg. Decreases also occurred in diastolic blood pressure, but were not statistically significant. In the LEAD studies with liraglutide, the decrease in blood pressure occurred within the first 2 weeks, before much weight loss had occurred. Thus, it seems unlikely that these improvements in blood pressure can be completely ascribed to decreases in body weight that were progressive over the 26-week duration of each study. This suggests that the reduction in blood pressure could be a direct effect of the GLP-1 mimetic. Potential mechanisms for this include a natriuretic effect as well as a direct vasorelaxant effect on the vascular system of GLP-1.
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In 3-year data for exenatide, a significant decrease in triglycerides, low-density lipoprotein cholesterol and total cholesterol, and a significant increase in high-density lipoprotein cholesterol were observed. A phase II study also demonstrated that liraglutide treatment was associated with improvements in triglycerides in addition to reductions in plasminogen activator inhibitor-1 (PAI-1). PAI-1 is a prothrombotic peptide that circulates in higher levels in patients with diabetes. Because it may contribute to increased cardiovascular risk, a reduction in PAI-1 is likely to be beneficial.
In summary, there appear to be beneficial effects of GLP-1 on cardiovascular disease risk factors, including blood pressure and lipids. Some of these beneficial effects are due to weight loss, but emerging data suggest that GLP-1 mimetics may have direct effects on the kidneys and vasculature. More research is needed, especially to explore direct cardioprotective effects of GLP-1.
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