Effect of a Dual PPAR α/γ agonist on Insulin Sensitivity in Patients of Type 2 Diabetes with Hypertriglyceridemia- Randomized double-blind placebo-controlled trial

Nimisha Jain, Shobhit Bhansali, Anura V. Kurpad, Meredith Hawkins, Akhilesh Sharma, Sandeep Kaur, Ashu Rastogi, Anil Bhansali

Research output: Contribution to journalArticle

Abstract

Saroglitazar is a dual PPAR-α/γ agonist approved for the treatment of diabetic dyslipidemia. In addition to reduction in atherogenic lipids, it may also contribute to improvement in insulin sensitivity through PPAR-α/γ agonism, which remains unexplored. We conducted a randomized, double-blind, placebo-controlled trial in treatment-naive T2DM individuals with serum triglyceride >150 mg/dL. Participants were randomized to receive either saroglitazar 4 mg or placebo (1:1) daily for 4 months (n = 30). Insulin sensitivity (SIclamp) was studied using hyperinsulinemic-euglycemic clamp at baseline and at 4 months. We observed a significant reduction in TG (p = 0.001), HbA1c (p = 0.019) and fasting plasma glucose (p = 0.019) and significant increase in HDL-C levels (p < 0.01) with saroglitazar compared to placebo. Further, patients on saroglitazar had a greater improvement in SIclamp (p = 0.026) with the effect persisting despite adjusting for baseline weight, TG, HDL-C and HbA1c (p = 0.002). This was accompanied with significant increase in HOMA-β (p = 0.01) in the saroglitazar group and change in HOMA-β showed a trend towards significance with SIclamp (r = 0.503, p = 0.056). However, change in SIclamp did not significantly correlate with reduction in HbA1c and TG. We conclude that saroglitazar effectively reduces hypertriglyceridemia and improves insulin sensitivity along with β-cell function by reduction in gluco-lipotoxicity and possibly directly through PPAR-γ agonism in patients ofT2DM with hypertriglyceridemia.

Original languageEnglish (US)
Article number19017
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Peroxisome Proliferator-Activated Receptors
Hypertriglyceridemia
Type 2 Diabetes Mellitus
Insulin Resistance
Placebos
Glucose Clamp Technique
Dyslipidemias
alpha-ethoxy-4-(2-(2-methyl-5-(4-methylthio)phenyl))-1H-pyrrol-1-yl)ethoxy))benzenepropanoic acid
Fasting
Triglycerides
Lipids
Weights and Measures
Glucose
Therapeutics
Serum

ASJC Scopus subject areas

  • General

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Effect of a Dual PPAR α/γ agonist on Insulin Sensitivity in Patients of Type 2 Diabetes with Hypertriglyceridemia- Randomized double-blind placebo-controlled trial. / Jain, Nimisha; Bhansali, Shobhit; Kurpad, Anura V.; Hawkins, Meredith; Sharma, Akhilesh; Kaur, Sandeep; Rastogi, Ashu; Bhansali, Anil.

In: Scientific Reports, Vol. 9, No. 1, 19017, 01.12.2019.

Research output: Contribution to journalArticle

Jain, Nimisha ; Bhansali, Shobhit ; Kurpad, Anura V. ; Hawkins, Meredith ; Sharma, Akhilesh ; Kaur, Sandeep ; Rastogi, Ashu ; Bhansali, Anil. / Effect of a Dual PPAR α/γ agonist on Insulin Sensitivity in Patients of Type 2 Diabetes with Hypertriglyceridemia- Randomized double-blind placebo-controlled trial. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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