Effect of saroglitazar 2 mg and 4 mg on glycemic control, lipid profile and cardiovascular disease risk in patients with type 2 diabetes mellitus: a 56-week, randomized, double blind, phase 3 study (PRESS XII study)

Abstract

Background: The potential for PPAR agonists to positively affect risk of cardiovascular disease in patients with type 2 diabetes (T2DM) is of persistent attention. The PRESS XII study primarily aimed to evaluate the efficacy and safety of saroglitazar (2 mg and 4 mg) as compared to pioglitazone 30 mg on glycemic control in patients with type 2 diabetes mellitus. Methods: In this randomized double-blind study, patients with T2DM [glycosylated hemoglobin (HbA1c) ≥ 7.5%] were enrolled from 39 sites in India. Patients received once-daily doses of either saroglitazar or pioglitazone (1:1:1 allocation ratio) for a total of 24 weeks. Patients were continued in a double blind extension period for an additional 32 weeks. Efficacy evaluations of glycemic parameters [HbA1c (Primary endpoint at week 24), FPG and PPG] and other lipid parameters (TG, LDL-C, VLDL-C, HDL-C, TC, Non HDL-C, Apo A1 and Apo B) were conducted at week 12, 24 and 56 and compared to the baseline levels. The efficacy analyses were performed by using paired t-test and ANCOVA model. Results: A total of 1155 patients were enrolled in this study. The baseline characteristics were similar between the three treatment groups. The within group mean (± SD) change in HbA1c (%) from baseline of the saroglitazar (2 mg and 4 mg) and pioglitazone treatment groups at week 24 were: − 1.38 ± 1.99 for saroglitazar 2 mg; − 1.47 ± 1.92 for saroglitazar 4 mg and − 1.41 ± 1.86 for pioglitazone, respectively. Statistically significant reduction from baseline in HbA1c was observed in each treatment group at week 24 with p-value < 0.016. There was a significant reduction in TG, LDL-C, VLDL-C, TC and Non HDL-C with a significant increase in HDL-C from baseline levels (< 0.016). Most of the AE's were 'mild' to 'moderate' in severity and were resolved by the completion of the study.

Peroxisome Proliferator-Activated Receptors and Their Novel Ligands as Candidates for the Treatment of Non-Alcoholic Fatty Liver Disease

“…In a post hoc analysis, elafibranor resolved NASH without fibrosis worsening and did not cause cardiac events [398]. Saroglitazar showed a potential to lower the cardiovascular risk in T2DM patients [418]. Pemafibrate is currently being tested for its effect on reducing cardiovascular events in diabetic patients with high TG levels in the PROMINENT study (NCT03071692) [390].…”

Structural Basis for Anti-non-alcoholic Fatty Liver Disease and Diabetic Dyslipidemia Drug Saroglitazar as a PPAR α/γ Dual Agonist

“…It also indicated that no significant changes can be observed in blood hemo-globin A1c (HbA1c), total/low density lipoprotein (LDL)/high density lipoprotein (HDL) cholesterol, and apolipoprotein-B. 32) With saroglitazar, there were no serious safety concerns, such as edema, carcinogenic potential, and cardiovascular side effects, except for a significant increase in serum creatinine. 32) Another recent study noted that saroglitazar treatment effectively improved glycemic control and lipid parameters over a 56-week period in patients with T2DM who received background metformin therapy.…”

Liver-targeting drugs and their effect on blood glucose and hepatic lipids

“…Clinical trials with tesaglitazar, aleglitazar and muraglitazar have been terminated due to side effects such as oedema and possible renal complications. Saroglitazar has been shown to significantly decrease both glucose and lipids [27] and has been approved recently in India for the treatment of NASH after the Phase III EVIDENCES-II trial showed histological improvement of NASH using liver biopsy after 52 weeks of treatment [28,29]; However, these data were only presented at conferences and there is only evidence of reduction in liver stiffness measured using FibroScan [29]. The Phase II EVIDENCES-IV trial is currently investigating the effect of saroglitazar in US individuals with NAFLD/ NASH.…”