title: A multicenter, prospective, randomized, double-blind study to evaluate the safety and efficacy of Saroglitazar 2 and 4 mg compared with placebo in type 2 diabetes mellitus patients having hypertriglyceridemia not controlled with atorvastatin therapy (PRESS VI).
abstract: BACKGROUND
  Dyslipidemia due to diabetes is characterized by hypertriglyceridemia and reduced levels of high-density lipoprotein cholesterol (HDL-C) and elevated or normal levels of low-density lipoprotein cholesterol (LDL-C) in type 2 diabetes mellitus (T2DM). The objectives of this Phase III study were to evaluate the safety, tolerability, and efficacy of saroglitazar (ZYH1) 2-mg and 4-mg tablets (Lipaglyn™; Zydus Cadila, Ahmedabad, India) compared with placebo in patients with diabetic dyslipidemia who are not controlled with atorvastatin 10 mg therapy.
  
  
  METHODS
  This was a 16-week prospective, multicenter, randomized, double-blind, placebo controlled, three-arm Phase III study in subjects with hypertriglyceridemia (>200 and <500 mg/dL) with T2DM not controlled with atorvastatin 10 mg. The study consisted of a run-in period of 4 weeks of life-style modification followed by 12 weeks of treatment with saroglitazar (2-mg or 4-mg) or placebo tablets. The primary end point was the change in plasma triglyceride level compared with baseline and the placebo arm at the end of Week 12. The secondary exploratory end points were change in lipid profile and fasting plasma glucose at Week 12. In total, 302 subjects were randomized to receive one of the treatments, saroglitazar 2 mg (n=101) or saroglitazar 4 mg (n=99), or matching placebo (n=102). Patients who received study medication and had undergone at least one post baseline efficacy evaluation were included in the efficacy analysis.
  
  
  RESULTS
  At Week 12, saroglitazar 2-mg and 4-mg tablets significantly reduced mean plasma triglyceride levels by -45.5±3.03% and -46.7±3.02% (mean±SE), respectively, and the difference was significant (P<0.001) compared with placebo. Saroglitazar 2 mg demonstrated significant decrease in levels of non-HDL-C, very LDL-C, total cholesterol, and fasting plasma glucose. Additionally, saroglitazar 4 mg also significantly reduced LDL-C and apolipoprotein B levels. Saroglitazar was found to be safe and well tolerated by patients.
  
  
  CONCLUSIONS
  Saroglitazar appeared to be an effective and safe therapeutic option for improving hypertriglyceridemia in patients with T2DM.
authors.affiliation: 1 Clinical R & D, Cadila Healthcare Ltd. , Ahmedabad, India .
authors.forename: Rajendrakumar H
authors.initials: RH
authors.lastname: Jani
authors.forename: Vikas
authors.initials: V
authors.lastname: Pai
authors.forename: Pramod
authors.initials: P
authors.lastname: Jha
authors.forename: Gunjan
authors.initials: G
authors.lastname: Jariwala
authors.forename: Satinath
authors.initials: S
authors.lastname: Mukhopadhyay
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
authors.forename: Shashank
authors.initials: S
authors.lastname: Joshi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000517:prevention & control*; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D010666:Phenylpropionates / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D040242:Risk Reduction Behavior; D017211:Treatment Failure; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010666:Phenylpropionates; D011758:Pyrroles; D014280:Triglycerides; D000069059:Atorvastatin; C000588741:saroglitazar