Atorvastatin and gemfibrozil decrease inflammation in diabetes
MedWire News: Atorvastatin and gemfibrozil have positive, complementary effects on inflammatory markers in patients with diabetes, research shows.
Atorvastatin was more effective at reducing lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, whereas gemfibrozil was more effective at lowering C-reactive protein (CRP) levels.
These results suggest the combination could delay the atherogenic process by different, complementary pathways, according to Antonio Pérez (Hospital de la Santa Creu i Sant Pau, Barcelona, Spain) and colleagues in the journal of Diabetes Research and Clinical Practice.
Patients with diabetes have an excess risk for cardiovascular events, but the risk is not fully explained by classical risk factors, such as dyslipidemia, explain the researchers.
Inflammation is frequently observed in diabetic patients, and research suggests it might play a role in the development of macrovascular complications.
In this randomized, cross-over, open-label study, the researchers assessed the impact of combined lipid-lowering therapy with atorvastatin and gemfibrozil on inflammatory markers in patients with well controlled Type 2 diabetes.
In total, 44 patients were treated with atorvastatin 10-20 mg/day for 12 weeks, gemfibrozil 900-1200 mg/day for another 12 weeks, and with both drugs at these dosages for 12 weeks of combined treatment.
Gemfibrozil, alone or with atorvastatin, significantly reduced CRP levels in all patients. When used alone, gemfibrozil reduced CRP levels from 2.34 mg/l at baseline to 1.37 mg/l after 12 weeks of therapy.
Atorvastatin, on the other hand, reduced CRP only in patients with CRP levels >2.0 mg/l at baseline.
Lp-PLA2 activity was reduced by atorvastatin, both on its own and when used in combination with gemfibrozil, but not by gemfibrozil alone. When used as monotherapy, atorvastatin reduced Lp-PLA2 activity from 14.5 to 12.7 µmol/ml/min after 12 weeks of treatment.
The researchers note that gemfibrozil is significantly less effective than atorvastatin in reducing low-density lipoprotein cholesterol levels and it is known that statins reduce Lp-PLA2 mass and activity in proportion to their cholesterol-lowering effects.
Both drugs increased secretory phospholipase A2 levels, whereas gemfibrozil alone modified interleukin 8 levels.
No change in tumor necrosis factor-α or monocyte chemotactic protein 1 activity was seen, however.
The reduction in independent inflammatory markers suggests that combination therapy with the lipid-lowering drugs could reduce the risk of macrovascular complications particularly affected by inflammation, conclude the researchers.
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