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Combined Use of Rosiglitazone and Fenofibrate in Patients With Type 2 Diabetes

Prevention of Fluid Retention

  1. Guenther Boden,
  2. Carol Homko,
  3. Maria Mozzoli,
  4. Meijuan Zhang,
  5. Karen Kresge and
  6. Peter Cheung
  1. From the Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Unit, Temple University School of Medicine, Philadelphia, Pennsylvania
  1. Address correspondence and reprint requests to Guenther Boden, MD, Temple University Hospital, 3401 North Broad St., Philadelphia, PA 19140. E-mail: bodengh{at}tuhs.temple.edu

Abstract

Elevated plasma free fatty acid (FFA) levels are responsible for much of the insulin resistance in obese patients with type 2 diabetes. To lower plasma FFA levels effectively and long term, we have treated eight obese patients with type 2 diabetes for 2 months with placebo followed by 2 months of treatment with a combination of rosiglitazone (RGZ) (8 mg/day) and fenofibrate (FFB) (160 mg/day) in a single-blind placebo-controlled study design. Compared with placebo, RGZ/FFB lowered mean 24-h plasma FFA levels 30% (P < 0.03) and mean 24-h glucose levels 23% (P < 0.03) and increased insulin-stimulated glucose uptake (glucose rate of disappearance [GRd], determined using euglycemic-hyperinsulinemic clamp) 442% (P < 0.01), oral glucose tolerance (area under the curve for 3-h oral glucose tolerance test) 28% (P < 0.05), and plasma adiponectin levels 218% (P < 0.01). These RGZ/FFB results were compared with results obtained in five patients treated with RGZ alone. RGZ/FFB prevented the fluid retention usually associated with RGZ (−1.6 vs. 5.6%, P < 0.05), lowered fasting plasma FFA more effectively than RGZ alone (−22 vs. 5%, P < 0.05), and tended to be more effective than RGZ alone in lowering A1C (−0.9 vs. −0.4%) and triglyceride levels (−38 vs. −5%) and increasing GRd (442 vs. 330%). We conclude that RGZ/FFB is a promising new therapy for type 2 diabetes that lowers plasma FFA more than RGZ alone and in contrast to RGZ does not cause water retention and weight gain.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted October 6, 2006.
    • Received April 11, 2006.
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