Pleiotropic Action of Short-Term Metformin and Fenofibrate Treatment, Combined With Lifestyle Intervention, in Type 2 Diabetic Patients With Mixed Dyslipidemia |
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Authors: | Maciej Pruski Robert Krysiak Boguslaw Okopien |
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Affiliation: | From the Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Katowice, Poland. |
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Abstract: | OBJECTIVETo compare the effect of short-term metformin and fenofibrate treatment, administered alone or in sequence, on glucose and lipid metabolism, cardiovascular risk factors, and monocyte cytokine release in type 2 diabetic patients with mixed dyslipidemia.RESEARCH DESIGN AND METHODSWe studied 128 type 2 diabetic patients with mixed dyslipidemia complying throughout the study with lifestyle intervention who were randomized twice, initially to either metformin or placebo, and then to micronized fenofibrate or placebo.RESULTSFenofibrate alleviated diabetic dyslipidemia–induced changes in plasma high-sensitivity C-reactive protein, fibrinogen, and plasminogen activator inhibitor (PAI)-1 and in monocyte cytokine release, whereas metformin or lifestyle intervention improved mainly glucose and lipid metabolism. The strongest pleiotropic effect was observed when fenofibrate was added to metformin.CONCLUSIONSFenofibrate, particularly administered together with metformin, is superior to metformin and lifestyle intervention in exhibiting beneficial effects on systemic inflammation, hemostasis, and monocyte secretory function in type 2 diabetic patients with mixed dyslipidemia.Peroxisome proliferator–activated receptor (PPAR)-α activators (fibrates) administered to patients with dyslipidemia (1–4) or early glucose metabolism abnormalities (5) produce many non–lipid-related effects, including anti-inflammatory, antioxidant, and antithrombotic actions and improvement in endothelial function. Apart from normalizing glucose metabolism, metformin, the only oral antidiabetic medication shown to decrease cardiovascular events independent of glycemic control (6), improved dyslipidemia, hemostasis, and systemic inflammation (7). To the best of our knowledge, no previous clinical study has ever compared clinical benefits of metformin and fibrates when it comes to their pleiotropic effects and assessed whether metformin-fibrate combination is superior to treatment with only one of these drugs. |
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