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Abrogation of postprandial triglyceridemia with dual PPAR α/γ agonist in type 2 diabetes mellitus: a randomized, placebo-controlled study

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Abstract

Aims

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.

Methods

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.

Results

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.

Conclusions

The saroglitazar treatment significantly improved postprandial TGs in people with diabetic dyslipidemia.

Trial registration

Clinical Trial Registry of India; trial Registration No.: CTRI/2015/06/005845 and Date of registration: June 02, 2015.

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Acknowledgements

This study was sponsored and funded by Cadila Healthcare Limited, a Zydus Group Company, Ahmedabad, Gujarat, India.

Author information

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.

Correspondence to Deven V. Parmar.

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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.

Ethics approval

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.

Informed consent

All participants gave written informed consent.

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Rastogi, A., Dunbar, R.L., Thacker, H.P. et al. Abrogation of postprandial triglyceridemia with dual PPAR α/γ agonist in type 2 diabetes mellitus: a randomized, placebo-controlled study. Acta Diabetol (2020). https://doi.org/10.1007/s00592-020-01487-8

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Keywords

  • PPARs
  • Dyslipidemias
  • Triglyceride
  • Diabetes
  • Clinical trial