A Multicenter, Prospective, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of Saroglitazar 2 and 4 mg Compared to Pioglitazone 45 mg in Diabetic Dyslipidemia (PRESS V).

Vikas Pai,Shashank Joshi,Dinesh Kamath,A Paneerselvam,Pankaj Patel,Satinath Mukhopadhyay,Dhiraj Gambhire,Rajendrakumar H Jani,V Shankar,Anil Bhansali

doi:10.1177/1932296813518680

Abstract

Dual PPARα/γ can improve both metabolic effects and minimized the side effects caused by either PPARα or PPARγ agonist. The PRESS V study was aimed to evaluate the safety, tolerability, and efficacy of saroglitazar 2 mg and 4 mg capsules (Lipaglyn™; Zydus Code: ZYH1) as compared to high dose pioglitazone in patients with diabetic dyslipidemia. In this 26-week double-blind, parallel arm, phase 3 study patients with hypertriglyceridemia with type 2 diabetes mellitus (BMI > 23 kg/m2; hypertriglyceridemia: TG > 200 to 400 mg/dL; glycosylated hemoglobin [HbA1c] >7 to 9%) were enrolled from 14 sites in India. After 2 weeks of lifestyle modification, 122 patients were randomized double-blind to 24-week treatment with the study drugs (saroglitazar 2 mg or 4 mg or pioglitazone 45 mg once daily) in a 1:1:1 ratio. The primary end point was change in plasma triglyceride level at week 24. The secondary end points were change in lipid profile and fasting plasma glucose at week 24. Patients who received study medication and had undergone at least 1 postbaseline efficacy evaluation were included in the efficacy analysis. All randomized patients who received at least a single dose were included for safety evaluation. The efficacy analysis included 109 patients (n = 37 in saroglitazar 2 mg; n = 39 in saroglitazar 4 mg; n = 33 in pioglitazone). Saroglitazar 2 mg and 4 mg significantly reduced (P < .001) plasma triglyceride from baseline by 26.4% (absolute change ± SD: −78.2 ± 81.98 mg/dL) and 45% (absolute change ± SD −115.4 ± 68.11 mg/dL), respectively, as compared to pioglitazone -15.5% (absolute change ± SD: −33.3 ± 162.41 mg/dL) at week 24. Saroglitazar 4 mg treatment also demonstrated marked decrease in low-density lipoprotein (5%), very-low-density lipoprotein (45.5%), total cholesterol (7.7%), and apolipoprotein-B (10.9%). Saroglitazar treatment was generally safe and well tolerated. No serious adverse events were reported in saroglitazar treatment arm and no persistent change in laboratory parameters. Saroglitazar appeared to be an effective and safe therapeutic option for improving hypertriglyceridemia in patients with type 2 diabetes mellitus.

Highlights

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in individuals with type 2 diabetes mellitus and responsible for 75% of deaths among type 2 diabetes patients.[1,2] There is 2- to 4-fold increase in cardiovascular events when compared with nondiabetic patients.[3,4,5,6]
The study consisted of a 2-week run-in period including lifestyle modification to wash out previous medications known to affect lipid levels, followed by a double-blind treatment period for 24 weeks with either saroglitazar (2 or 4 mg capsules, Cadila Healthcare Limited, India) or pioglitazone 45 mg capsules, as an active comparator; and a follow-up visit for safety assessment at 24 week after the last treatment
Patients were recruited from July 21, 2009, to January 27, 2011, from hospital clinics and practicing physicians specialized in the treatment of diabetes

Summary

Introduction

Cardiovascular disease (CVD) is the major cause of morbidity and mortality in individuals with type 2 diabetes mellitus and responsible for 75% of deaths among type 2 diabetes patients.[1,2] There is 2- to 4-fold increase in cardiovascular events (coronary heart disease, stroke and peripheral vascular disease) when compared with nondiabetic patients.[3,4,5,6] This risk is attributed to many cardiovascular risk factors including dyslipidemia and hyperglycemia.[7] Analysis of 2 intensive glycemic control clinical studies in type 2 diabetes mellitus (Action to Control Cardiovascular Risk in Diabetes [ACCORD]8 and Action in Diabetes and Vascular Disease: Preterax and Doamicron Modified Release Controlled Evaluation [ADVANCE]9) has demonstrated an improvement in microvascular events, but not in macrovascular. Prospective Randomized Efficacy and Safety of Saroglitazar (PRESS V) was designed to establish therapeutic effect of saroglitazar on triglycerides and other lipid and glucose profile with expectation of favorable safety and tolerability in type 2 diabetes

Methods

Results

Conclusion