Abrogation of postprandial triglyceridemia with dual PPAR α/γ agonist in type 2 diabetes mellitus: a randomized, placebo-controlled study
- 22 Downloads
Lowering postprandial lipemia may mitigate cardiovascular risk in patients with diabetic dyslipidemia. This study was aimed to investigate whether saroglitazar suppresses postprandial lipemia in patients with diabetes and dyslipidemia.
This was a 12-week, prospective, multicenter, randomized, double-blinded, placebo-controlled study of saroglitazar in patients with diabetes and dyslipidemia. Thirty patients were randomized (1:1) to receive saroglitazar 4 mg or placebo orally once daily with metformin for 12 weeks. The primary endpoint was change in plasma triglyceride (TG) area under the curve (AUC) on a standardized 8-h fat tolerance test.
Thirty participants were randomized for interventions and eventually data of 19 participants qualified for per protocol analyses. Mean (SD) age in saroglitazar was 53.1 (8.8) years and 54.9 (7.7) years in placebo group. After 12 weeks, saroglitazar significantly lowered postprandial TG-AUC by − 458.3 (144.0) (− 25.7%, 95% CI − 765.1 to − 151.4) versus an increase of + 10.9 (157.9) (+ 0.5%, 95% CI − 325.6 to 347.3) mg/dL h in placebo group (P < 0.05). Saroglitazar lowered postprandial TG incremental AUC versus placebo: − 329.4 (89.9) (− 59%) versus + 80.4 (99.4) (+ 10%) mg/dL h (P < 0.05). HbA1c (%) decreased by − 0.36 (0.42) in the saroglitazar group as compared to an increase of + 1.26 (0.46) (P < 0.05) with placebo.
The saroglitazar treatment significantly improved postprandial TGs in people with diabetic dyslipidemia.
Clinical Trial Registry of India; trial Registration No.: CTRI/2015/06/005845 and Date of registration: June 02, 2015.
KeywordsPPARs Dyslipidemias Triglyceride Diabetes Clinical trial
This study was sponsored and funded by Cadila Healthcare Limited, a Zydus Group Company, Ahmedabad, Gujarat, India.
Dr. Deven, Dr. Jayesh Bhatt and Krupi Parmar participated in protocol development, planning, supervision of clinical operations, collection of the data, analysis of the data, interpretation of the results and writing the report. Dr. RL Dunbar participated in the analysis and interpretation of data and manuscript preparation. Dr. Ashu Rastogi and Dr. Hemant P Thacker participated in clinical protocol development, conduct of the fat tolerance test, clinical care of the participants, collection of data, interpretation of results and preparation of this manuscript. All authors accept full responsibility for the study, had full access to all the data and take responsibility for the integrity of the data and the accuracy of the analysis. The corresponding author had the final responsibility to submit for publication. The authors would also like to thank Clinical Operation and Medical Affairs Department, Zydus Research Center, Ahmedabad, especially Dr. Manjunath K for scientific support, Dr. Chintan Shah for data management and Ms. Pooja Trivedi for statistical support.
Compliance with ethical standards
Conflict of interest
Dr. Jayesh Bhatt and Krupi Parmar are employees of Cadila Healthcare Limited, Ahmedabad. During the work carried out, Dr. Deven was the employee of Cadila Healthcare Limited, Ahmedabad, and currently is associated with Zydus Discovery DMCC, Dubai. During editing, Dr. Dunbar was employed by ICON plc and is presently employed by Amarin where he will own stock.
The Institutional Ethics Committee of PGIMER, Chandigarh, date of approval March 10, 2015, and the Clinical Trial Ethics Committee, Bhatia Hospital, Tardeo Road, Mumbai, date of approval August 03, 2015, had reviewed and approved the study. The study complied with the ethical principles underlying the Declaration of Helsinki.
All participants gave written informed consent.
- 10.Chappuis B, Braun M, Stettler C et al (2007) Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study. Diabetes Metab Res Rev 23(5):392–399PubMedCrossRefGoogle Scholar
- 14.Jain MR, Giri SR, Trivedi C et al (2015) Saroglitazar, a novel PPAR α/γ agonist with predominant PPAR α activity, shows lipid-lowering and insulin-sensitizing effects in preclinical models. Pharma Res Perspect 3(3):1–14Google Scholar
- 19.Shiang KD (2004) The SAS® calculations of areas under the curve (AUC) for multiple metabolic readings. https://www.lexjansen.com/wuss/2004/posters/c_post_the_sas_calculations_.pdf. Accessed 10 May 2017
- 24.Jani RH, Pai V, Jha P et al (2014) 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). Diabetes Technol Ther 16(2):63–71PubMedPubMedCentralCrossRefGoogle Scholar
- 39.Daniel G, Digenio A, Alexander V et al (2017) The approach study: a randomized, double-blind, placebo-controlled, phase 3 study of volanesorsen administered subcutaneously to patients with familial chylomicronemia syndrome (FCS). Atherosclerosis 263:e10Google Scholar