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.
OBJECTIVE
Ragaglitazar is a novel insulin sensitizer with dual peroxisome proliferator-activated receptor (PPAR)-gamma and PPAR-alpha 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.


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.
Saad
Mohammed F
MF
UCLA Diabetes Center, 330 South Garfield Avenue, Suite #308, Alhambra, CA 91801, USA. msaad@mednet.ucla.edu
Greco
Susan
S
Osei
Kwame
K
Lewin
Andrew J
AJ
Edwards
Christopher
C
Nunez
Margarita
M
Reinhardt
Rickey R
RR
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000627:therapeutic use*; D010666:Phenylpropionates / Q000627:therapeutic use*; D010919:Placebos; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D008055:Lipids; D008074:Lipoproteins; D010078:Oxazines; D010666:Phenylpropionates; D010919:Placebos; D014280:Triglycerides; C432703:ragaglitazar