Ragaglitazar Improves Glycemic Control and Lipid Profile in Type 2 Diabetic Subjects
A 12-week, double-blind, placebo-controlled dose-ranging study with an open pioglitazone arm
- Mohammed F. Saad, MD1,
- Susan Greco, MD2,
- Kwame Osei, MD3,
- Andrew J. Lewin, MD4,
- Christopher Edwards, MD5,
- Margarita Nunez, MD6,
- Rickey R. Reinhardt, MD7 and
- for the Ragaglitazar Dose-Ranging Study Group*
- 1UCLA Diabetes Center, Alhambra, California
- 2Jacksonville Center for Clinical Research, Jacksonville, Florida
- 3Ohio State University Medical Center, Columbus, Ohio
- 4National Research Institute, Los Angeles, California
- 5Primary Care Specialists, Ocoee, Florida
- 6ICSL-Clinical Studies, St. Petersburg, Florida
- 7Novo Nordisk Pharmaceuticals, Princeton, New Jersey
- Address correspondence and reprint requests to Mohammed F. Saad, MD, UCLA Diabetes Center, 330 South Garfield Ave., Suite #308, Alhambra, CA 91801. E-mail: msaad{at}mednet.ucla.edu
Abstract
OBJECTIVE—Ragaglitazar is a novel insulin sensitizer with dual peroxisome proliferator-activated receptor (PPAR)-γ and PPAR-α stimulating activities that improve plasma glucose and lipid profiles. The aim of the present dose-ranging study was to assess the efficacy and safety of ragaglitazar in patients with type 2 diabetes.
RESEARCH DESIGN AND METHODS—This study included 177 hypertriglyceridemic type 2 diabetic subjects who participated in a 12-week, double-blind, parallel, randomized, placebo-controlled dose-ranging study (open pioglitazone arm). Subjects received ragaglitazar (0.1, 1, 4, or 10 mg), placebo, or pioglitazone (45 mg). Efficacy parameters included fasting plasma levels of triglycerides and glucose (FPG) along with other lipid levels, A1C, and insulin.
RESULTS—Ragaglitazar in doses of 1, 4, and 10 mg resulted in a significant decrease from baseline as compared with placebo in FPG (−48, −74, −77 mg/dl) and triglycerides (−40, −62, −51%), free fatty acids (−36, −54, −62%), apolipoprotein B (−13, −29, −25%), LDL cholesterol (−14 and −19% for 4- and 10-mg groups), and total cholesterol (−16 and −15% for 4 and 10 mg) and a significant increase in HDL cholesterol (20 and 31% for 1- and 4-mg groups, respectively). Changes in triglycerides and FPG for pioglitazone treatment were similar to 1 mg ragaglitazar. Mean A1C values of the 1-, 4-, and 10-mg ragaglitazar and pioglitazone groups were significantly reduced compared with placebo (−0.5, −1.3, −1.1, and −0.3%, respectively). Common adverse events were edema, weight increase, leukopenia, and anemia.
CONCLUSIONS—Ragaglitazar provided glycemic control that was comparable with that of pioglitazone and, compared with placebo, provided significant improvement in the lipid profile.
- ANC, absolute neutrophil count
- CVD, cardiovascular disease
- FFA, free fatty acid
- FPG, fasting plasma glucose
- OHA, oral hypoglycemic agent
- PPAR, peroxisome proliferator-activated receptor
- TEAE, treatment emergent adverse event
- WBC, white blood cell
Footnotes
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M.F.S., S.G., and A.J.L. have received grant support from Novo Nordisk Pharmaceuticals.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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↵* A complete list of the Ragaglitazar Dose-Ranging Study Group can be found in the appendix.
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- Accepted March 1, 2004.
- Received October 26, 2003.
- DIABETES CARE
