학술논문
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)
Document Type
Clinical report
Author
Krishnappa, Manjunath; Patil, Kishor; Parmar, Krupi; Trivedi, Purav; Mody, Nirali; Shah, Chintan; Faldu, Khushboo; Maroo, Sanjay; Desai, Piyush; Fatania, Kamlesh; Murthy, Satyanarayan; Balamurugan, R.; Agarwal, Manish; Singh, K. P.; Kalra, G. S.; Khandelwal, Vipul; Singwala, Ashish; Thacker, Hemant; Tulle, Rahul; Rao, Harish; Kumbla, Mukund; Singh, Parminder; Khatri, Ashok; Agrawal, Sumit; Sarkar, R. N.; Agarwal, Dinesh; Bhatia, Girish; Agarwal, R. P.; Kumar, Surender; Vamsi Krishna, P. R.; Ajmani, Ajay Kumar; Asalkar, Amit; Basu, Indraneel; Chatterjee, Sudip; Pavithran, Vinod Kumar; Das, Rupam; Dharmadhikari, Aniruddha; Vardhan, Vikram; Madusudhan Babu, M.; Sengupta, Nilanjan; Abkari, Srirang; Harikrishna, R.; Chovatia, Rashmi
Source
Cardiovascular Diabetology. June 19, 2020, Vol. 19 Issue 1
Subject
Language
English
Abstract
Author(s): Manjunath Krishnappa[sup.1], Kishor Patil[sup.1], Krupi Parmar[sup.1], Purav Trivedi[sup.1], Nirali Mody[sup.1], Chintan Shah[sup.1], Khushboo Faldu[sup.1], Sanjay Maroo[sup.1], Piyush Desai, Kamlesh Fatania, Satyanarayan Murthy, R. Balamurugan, Manish Agarwal, K. P. Singh, [...]
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) [greater than or equai to] 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 ([+ or -] SD) change in HbA1c (%) from baseline of the saroglitazar (2 mg and 4 mg) and pioglitazone treatment groups at week 24 were: - 1.38 [+ or -] 1.99 for saroglitazar 2 mg; - 1.47 [+ or -] 1.92 for saroglitazar 4 mg and - 1.41 [+ or -] 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. Conclusions Saroglitazar effectively improved glycemic control and lipid parameters over 56 weeks in patients of T2DM receiving background metformin therapy and has a promising potential to reduce the cardiovascular risk in T2DM patients. Trial registration CTRI/2015/09/006203, dated 22/09/2015 Keywords: Type 2 diabetes mellitus, Saroglitazar, Peroxisome proliferator-activated receptors (PPAR [alpha]/[gamma]) agonist, Pioglitazone, Cardiovascular disease risk
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) [greater than or equai to] 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 ([+ or -] SD) change in HbA1c (%) from baseline of the saroglitazar (2 mg and 4 mg) and pioglitazone treatment groups at week 24 were: - 1.38 [+ or -] 1.99 for saroglitazar 2 mg; - 1.47 [+ or -] 1.92 for saroglitazar 4 mg and - 1.41 [+ or -] 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. Conclusions Saroglitazar effectively improved glycemic control and lipid parameters over 56 weeks in patients of T2DM receiving background metformin therapy and has a promising potential to reduce the cardiovascular risk in T2DM patients. Trial registration CTRI/2015/09/006203, dated 22/09/2015 Keywords: Type 2 diabetes mellitus, Saroglitazar, Peroxisome proliferator-activated receptors (PPAR [alpha]/[gamma]) agonist, Pioglitazone, Cardiovascular disease risk