Combined use of rosiglitazone and fenofibrate in patients with type 2 diabetes: prevention of fluid retention.
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(R)(d)], 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.
Boden
Guenther
G
Division of Endocrinology/Diabetes/Metabolism, Clinical Research Unit, Temple University School of Medicine, Philadelphia, PA, USA. bodengh@tuhs.temple.edu
Homko
Carol
C
Mozzoli
Maria
M
Zhang
Meijuan
M
Kresge
Karen
K
Cheung
Peter
P
D052242:Adiponectin / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001834:Body Water / Q000187:drug effects / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010919:Placebos; D000077154:Rosiglitazone; D016037:Single-Blind Method; D045162:Thiazolidinediones / Q000627:therapeutic use*
D052242:Adiponectin; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D011345:Fenofibrate