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

Prevention of Fluid Retention

From the Division of Endocrinology/Diabetes/Metabolism and the Clinical Research Unit, Temple University School of Medicine, Philadelphia, Pennsylvania

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

Abbreviations: CRC, clinical research center; EGP, endogenous glucose production; FFA, free fatty acid; FFB, fenofibrate; GIR, glucose infusion rate; OGTT, oral glucose tolerance test; PPAR, peroxisome proliferator–activated receptor; RGZ, rosiglitazone; TZD, thiazolidinedione

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 [G_Rd], 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 G_Rd (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.

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				J. S. Stroup Comment on: Boden et al. (2007) Combined Use of Rosiglitazone and Fenofibrate in Patients with Type 2 Diabetes: Prevention of Fluid Retention: Diabetes 56:248-255 Diabetes, May 1, 2007; 56(5): e1 - e1. [Full Text] [PDF]

				J. Karalliedde and G.C. Viberti Comment on: Boden et al. (2007) Combined Use of Rosiglitazone and Fenofibrate in Patients with Type 2 Diabetes: Prevention of Fluid Retention: Diabetes 56:248-255 Diabetes, May 1, 2007; 56(5): e3 - e3. [Full Text] [PDF]

				G. Boden Response to Comment on: Boden et al. (2007) Combined Use of Rosiglitazone and Fenofibrate in Patients with Type 2 Diabetes: Prevention of Fluid Retention: Diabetes 56:248-255 Diabetes, May 1, 2007; 56(5): e4 - e4. [Full Text] [PDF]