Saroglitazar, a Dual PPAR α/γ Agonist, Improves Atherogenic Dyslipidemia in Patients With Non-Cirrhotic Nonalcoholic Fatty Liver Disease: A Pooled Analysis.

Shiv Kumar Sarin, Arun J Sanyal, Mohammad Shadab Siddiqui, Deven Parmar, Farheen Sheikh, Laura Cisneros, Samer Gawrieh, Taufik Momin, Ajay Duseja

Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2023;21(10):2597-2605.e2

PMID: 36731585

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND & AIMS

Cardiovascular disease is the leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the effects of saroglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist, on serum lipids in patients with NAFLD.

METHODS

A total of 221 patients (saroglitazar, 130; placebo, 91) with NAFLD from phase 2 and 3 double-blinded placebo-controlled randomized clinical trials were pooled to assess the impact of saroglitazar magnesium 4 mg on traditional lipids, very low density lipoprotein cholesterol (VLDL-C), and small dense LDL-C (sdLDL-C). Change from baseline in lipid parameters was performed by using analysis of covariance including treatment as fixed effect and baseline value, diabetes, hypertension, and statin use as covariates.

RESULTS

Treatment with saroglitazar significantly improved total cholesterol (-17 mg/dL, 95% confidence interval [CI], -24 to 9; P < .001), triglyceride (-45 mg/dL, 95% CI, -60 to 31; P < .001), low-density lipoprotein cholesterol (-8 mg/dL, 95% CI, -15 to -1; P = .01), and VLDL-C (-8 mg/dL, -14 to -3; P < .001). Saroglitazar improved serum lipids as early as 4-6 weeks of initiation of therapy, and these effects persisted for duration of therapy. Saroglitazar also improved the highly atherogenic sdLDL-C (-10 mg/dL, -17 to -2; P = .01). In subgroup analysis of patients with either diabetes or hypertension, saroglitazar significantly improved serum lipids.

CONCLUSIONS

Saroglitazar improved the serum atherogenic lipoprotein profile in patients with NAFLD, irrespective of comorbid conditions and statin use. Saroglitazar has the potential to not only positively affect liver disease but also reduce cardiovascular risk in patients with NAFLD. (Trials registrations: CTRI 2015/10/006236, CTRI 173300410A0106, NCT03863574, and NCT03061721).

Address: Virginia Commonwealth University, Richmond, Virginia. Electronic address: [email protected].; Zydus Therapeutics Inc USA, Pennington, NJ. Electronic address: [email protected].; Zydus Therapeutics Inc USA, Pennington, NJ.; Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India.; Christus Muguerza Alta Especialidad, Monterrey, Mexico.; Indiana University School of Medicine, Indianapolis, Indiana.; Postgraduate Institute of Medical Education & Research, Chandigarh, India.; Virginia Commonwealth University, Richmond, Virginia.

DOI: 10.1016/j.cgh.2023.01.018

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MeSH Terms: Humans, Non-alcoholic Fatty Liver Disease, Diabetes Mellitus, Type 2, PPAR alpha, Hydroxymethylglutaryl-CoA Reductase Inhibitors, PPAR-gamma Agonists, Dyslipidemias, Triglycerides, Cholesterol, Hypertension