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The PRESS XII study primarily aimed to evaluate the efficacy and safety of saroglitazar (2\u00a0mg and 4\u00a0mg) as compared to pioglitazone 30\u00a0mg on glycemic control in patients with type 2 diabetes mellitus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this randomized double-blind study, patients with T2DM [glycosylated hemoglobin (HbA1c)\u2009\u2265\u20097.5%] 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\u00a0weeks. Patients were continued in a double blind extension period for an additional 32\u00a0weeks. 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 1155 patients were enrolled in this study. The baseline characteristics were similar between the three treatment groups. The within group mean (\u00b1\u2009SD) change in HbA1c (%) from baseline of the saroglitazar (2\u00a0mg and 4\u00a0mg) and pioglitazone treatment groups at week 24 were: \u2212\u20091.38\u2009\u00b1\u20091.99 for saroglitazar 2\u00a0mg; \u2212\u20091.47\u2009\u00b1\u20091.92 for saroglitazar 4\u00a0mg and \u2212\u20091.41\u2009\u00b1\u20091.86 for pioglitazone, respectively. Statistically significant reduction from baseline in HbA1c was observed in each treatment group at week 24 with p-value\u2009&lt;\u20090.016. 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 (&lt;\u20090.016). Most of the AE\u2019s were \u2018mild\u2019 to \u2018moderate\u2019 in severity and were resolved by the completion of the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Saroglitazar effectively improved glycemic control and lipid parameters over 56\u00a0weeks in patients of T2DM receiving background metformin therapy and has a promising potential to reduce the cardiovascular risk in T2DM patients.<\/jats:p><jats:p><jats:italic>Trial registration<\/jats:italic>CTRI\/2015\/09\/006203, dated 22\/09\/2015<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12933-020-01073-w","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T16:06:12Z","timestamp":1592582772000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Effect of saroglitazar 2\u00a0mg and 4\u00a0mg 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)"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8021-7004","authenticated-orcid":false,"given":"Manjunath","family":"Krishnappa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishor","family":"Patil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krupi","family":"Parmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purav","family":"Trivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirali","family":"Mody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chintan","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushboo","family":"Faldu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Maroo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the PRESS XII study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamlesh","family":"Fatania","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satyanarayan","family":"Murthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Balamurugan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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