Saroglitazar: A Comprehensive Pharmacological and Clinical Monograph of a First-in-Class Dual PPAR Agonist

Executive Summary

Saroglitazar represents a significant innovation in the management of complex metabolic disorders, emerging as the first and only approved agent in the "glitazar" class. Its unique pharmacological profile is defined by its action as a dual agonist of Peroxisome Proliferator-Activated Receptors (PPARs), with a carefully engineered balance of predominant PPAR-α and moderate PPAR-γ activity. This molecular design successfully uncouples potent therapeutic effects on lipid and glucose metabolism from the class-limiting adverse effects that led to the failure of previous dual agonists.

Clinically, Saroglitazar has established robust efficacy in its approved indications in India: diabetic dyslipidemia and Non-Alcoholic Fatty Liver Disease (NAFLD) / Non-Alcoholic Steatohepatitis (NASH). In diabetic dyslipidemia, head-to-head trials have demonstrated its superiority over the thiazolidinedione pioglitazone in improving atherogenic lipid profiles while maintaining comparable glycemic control. In NAFLD/NASH, clinical data from the EVIDENCES trial program has shown significant improvements in liver enzymes, hepatic fat content, and underlying metabolic drivers, positioning it as a promising disease-modifying therapy in a field with no approved treatments.

The drug's safety profile is a key differentiator. It is notably devoid of the weight gain and peripheral edema associated with potent PPAR-γ agonists and has shown a more favorable renal and hepatic safety profile compared to fibrates. While a mild increase in serum creatinine has been noted in some analyses, its non-renal route of excretion is a significant advantage for patients with comorbid diabetic nephropathy.

Developed indigenously by the Indian pharmaceutical company Zydus Lifesciences, Saroglitazar's regulatory journey is a landmark achievement. While its initial approval is confined to India, the company is pursuing a sophisticated global strategy focused on securing approval for orphan indications, such as Primary Biliary Cholangitis (PBC), in the United States and Europe. This approach, supported by Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), de-risks its international expansion. The ongoing pivotal, biopsy-driven trial in NASH with fibrosis will be a critical determinant of its future as a global therapeutic. If successful, Saroglitazar is poised to address significant unmet medical needs and could become a foundational therapy for a range of interconnected metabolic and hepatic diseases worldwide.

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Section 1: Molecular Profile and Pharmacology

This section establishes the fundamental scientific basis of Saroglitazar, detailing its chemical nature and the intricate molecular mechanisms that underpin its therapeutic effects.

[1.1. Chemical Identity and Physicochemical Properties]

Saroglitazar is a small molecule drug with a distinct chemical structure that sets it apart from previous generations of metabolic regulators. Its formal chemical identity and properties are foundational to understanding its pharmacological behavior.

The IUPAC name for Saroglitazar is (2S)-2-Ethoxy-3-[4-(2-{2-methyl-5-[4-(methylsulfanyl)phenyl]-1H-pyrrol-1-yl}ethoxy)phenyl]propanoic acid.[1] It has a chemical formula of

C25​H29​NO4​S, corresponding to an average molecular weight of 439.57 and a precise monoisotopic mass of 439.181729592.[2] For unambiguous identification in scientific and regulatory databases, it is assigned several unique identifiers:

• CAS Number: 495399-09-2 [1]
• DrugBank ID: DB13115 [1]
• PubChem CID: 60151560 [1]
• InChI Key: MRWFZSLZNUJVQW-DEOSSOPVSA-N [1]

From a chemical classification perspective, Saroglitazar belongs to the class of organic compounds known as phenylpyrroles, containing a benzene ring linked to a pyrrole ring. It also incorporates structural motifs of phenylpropanoic acids and thiophenol ethers.[2] Critically, its molecular architecture was intentionally designed as a non-thiazolidinedione (TZD) and non-fibric acid derivative.[3] This structural distinction is not merely academic; it represents a deliberate and strategic effort to separate the therapeutic benefits of PPAR agonism from the well-documented, class-specific adverse effects associated with older drugs. Traditional TZDs, which are potent PPAR-γ agonists, are linked to adverse events such as peripheral edema and weight gain.[5] Fibrates, which are PPAR-α agonists, carry risks of increased serum creatinine and potential hepatotoxicity.[8] By engineering a novel chemical scaffold devoid of the TZD ring or fibric acid structure, the developers hypothesized that they could retain the desired metabolic effects while minimizing these liabilities. This foundational design choice is central to the improved safety and tolerability profile observed in subsequent clinical investigations.[6]

Predicted physicochemical properties further characterize the molecule. With a very low predicted water solubility of 0.00149 mg/mL, a logP of 5.05, and a strongest acidic pKa of 3.73, Saroglitazar is a lipophilic, acidic molecule.[2] These properties influence its absorption, distribution, and formulation as an oral tablet.

[1.2. Mechanism of Action: Dual PPAR-α/γ Agonism]

Saroglitazar is the first agent in its class to achieve regulatory approval, functioning as a dual agonist of Peroxisome Proliferator-Activated Receptors (PPARs). These are nuclear receptors that act as transcription factors to regulate the expression of a multitude of genes involved in lipid and glucose metabolism.[1] Saroglitazar specifically targets two key subtypes: PPAR-α and PPAR-γ.[12]

The defining feature of Saroglitazar's mechanism is its unique activity ratio: it exhibits predominantly greater PPAR-α activity with moderate PPAR-γ activity.[3] This precise tuning of receptor engagement is the key to its clinical profile and its success where earlier, more balanced dual agonists failed. The distinct downstream effects of activating each receptor subtype are as follows:

• PPAR-α Mediated Effects (Lipid Metabolism): The predominant activation of PPAR-α is the primary driver of Saroglitazar's potent lipid-modifying effects. PPAR-α acts as a nutritional sensor, particularly in the liver, where its activation orchestrates a coordinated response to manage fatty acids.[14] This includes enhancing the beta-oxidation (burning) of fatty acids, increasing the activity of lipoprotein lipase (LPL) which clears triglyceride-rich lipoproteins from the circulation, and reducing the production of apolipoprotein C-III, a natural inhibitor of LPL.[8] The net result of these actions is a robust and clinically significant reduction in serum triglycerides, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) cholesterol, along with an increase in high-density lipoprotein (HDL) cholesterol.[11]
• PPAR-γ Mediated Effects (Glucose Metabolism): The moderate activation of PPAR-γ complements the lipid effects by improving insulin sensitivity and glycemic control. PPAR-γ activation modulates the transcription of genes involved in glucose uptake and utilization in peripheral tissues.[1] It also promotes the differentiation of preadipocytes into mature adipocytes, which are better equipped to safely store free fatty acids, thereby preventing their accumulation in ectopic sites like the liver and muscle where they contribute to insulin resistance.[3]

This "predominant α over moderate γ" activity ratio represents a clinical sweet spot. Historically, the development of dual PPAR agonists has been fraught with challenges. More balanced agonists, such as muraglitazar and tesaglitazar, showed promise in preclinical studies but ultimately failed in clinical development due to significant safety concerns, including cardiotoxicity and hepatotoxicity, largely attributed to potent PPAR-γ agonism.[15] Saroglitazar is the first glitazar to navigate this therapeutic window successfully. Its design allows it to achieve powerful lipid-lowering effects that are comparable to or even exceed those of pure PPAR-α agonists (fibrates), while the moderate PPAR-γ engagement provides meaningful insulin sensitization and glycemic improvement without triggering the full spectrum of potent PPAR-γ-mediated side effects like significant weight gain and edema.[6] This successful tuning of receptor activity explains why Saroglitazar is the first and only agent in its class to reach the market.

[1.3. Pharmacodynamic Profile]

The dual agonism of Saroglitazar translates into a broad spectrum of beneficial pharmacodynamic effects on key metabolic biomarkers, as demonstrated in both preclinical models and human clinical trials.

• Lipid Modulation: The most pronounced effect of Saroglitazar is on the lipid profile, particularly in patients with atherogenic diabetic dyslipidemia. In pivotal clinical trials, the standard 4 mg daily dose has been shown to produce substantial reductions in multiple lipid parameters. This includes reductions in triglycerides of up to 45-55%, LDL-cholesterol by 5-16.4%, total cholesterol by 7.7-19%, and non-HDL cholesterol by 23.4%.[8] Concurrently, it effectively raises levels of HDL cholesterol, addressing a key component of diabetic dyslipidemia.[4]
• Glycemic Control: Through its moderate PPAR-γ activity, Saroglitazar improves insulin resistance and lowers blood glucose levels. Clinical studies have consistently reported reductions in fasting plasma glucose. In a post-marketing surveillance study, its addition to existing antidiabetic therapy resulted in an absolute reduction in HbA1c of 0.9%, a clinically meaningful improvement in long-term glycemic control.[1]
• Other Metabolic Biomarkers: Preclinical studies in animal models have revealed additional beneficial effects. In Zucker fa/fa rats, a model of obesity and insulin resistance, Saroglitazar treatment led to a 62.1% increase in serum adiponectin, a hormone secreted by fat cells that enhances insulin sensitivity.[3] The same study also observed a significant decrease in systolic blood pressure of 22 mmHg, suggesting potential cardiovascular benefits beyond lipid and glucose control.[3]

This comprehensive pharmacodynamic profile, simultaneously addressing dyslipidemia, hyperglycemia, insulin resistance, and potentially blood pressure, positions Saroglitazar not merely as a lipid-lowering or anti-diabetic drug, but as a holistic treatment for metabolic syndrome.[20] While its approved indications are specific, its mechanism of action targets the interconnected pathologies that define this cluster of conditions, suggesting a broader therapeutic utility that may be explored in future clinical development.

[1.4. Pharmacokinetics: Absorption, Distribution, Metabolism, and Excretion (ADME)]

The pharmacokinetic profile of Saroglitazar describes its disposition within the body, which supports its clinical use and dosing regimen. The ADME properties have been characterized in Phase 1 studies in healthy human volunteers.

• Absorption: Following oral administration, Saroglitazar is rapidly and well-absorbed. The median time to reach peak plasma concentration (tmax​) is less than 1 hour under fasting conditions, indicating a quick onset of systemic exposure.[13] The effect of food on its absorption is minimal and has been shown to be inconsistent between males and females, suggesting it can be administered without strict regard to meals, although it is typically recommended to be taken before the first meal of the day.[13]
• Distribution: Once in the systemic circulation, Saroglitazar is highly bound to plasma proteins, with a protein binding of approximately 99%.[1] This high degree of binding influences its distribution into tissues and its availability at the site of action.
• Metabolism: Saroglitazar is metabolized in the liver. The primary enzymes responsible for its biotransformation are from the Cytochrome P450 system, specifically CYP2C8 and CYP3A4.[1] This metabolic pathway is a critical consideration for potential drug-drug interactions with other medications that are substrates, inhibitors, or inducers of these same enzymes.
• Excretion: The primary route of elimination for Saroglitazar and its metabolites is via the bile duct into the feces (hepatobiliary excretion).[1] A crucial and defining feature of its pharmacokinetic profile is that it is not eliminated via the renal route. Studies have confirmed that no quantifiable concentrations of the parent drug are found in urine, even at very high doses.[13] The average terminal elimination half-life ( t1/2​) is approximately 5.6 hours, a duration that is well-suited for a convenient once-daily dosing schedule.[1]

The non-renal excretion pathway of Saroglitazar represents a significant and perhaps underappreciated clinical advantage. The target patient population—individuals with type 2 diabetes and dyslipidemia—has a high prevalence of comorbid diabetic nephropathy. Many medications, including some fibrates, require dose adjustments or are contraindicated in patients with impaired renal function due to their reliance on the kidneys for clearance.[8] Saroglitazar's independence from this elimination route makes it a theoretically safer and more straightforward option in this complex and vulnerable patient population. This distinction could be a key factor in therapeutic decision-making, particularly for patients with progressing kidney disease. The completion of a dedicated clinical trial to evaluate its pharmacokinetics in subjects with severe renal impairment (NCT04446507) underscores the sponsor's recognition of this potential advantage and their effort to formally characterize it.[23]

Table 1: Summary of Saroglitazar's Pharmacokinetic Parameters

Parameter	Value / Description	Clinical Implication	Source(s)
Tmax​ (Time to Peak Concentration)	< 1 hour (median)	Rapid absorption and onset of systemic exposure.	13
Protein Binding	~99%	High binding influences distribution and potential for displacement interactions.	1
Elimination Half-life (t1/2​)	5.6 hours (average)	Supports a convenient once-daily dosing regimen without significant accumulation.	1
Primary Metabolism Pathway	Hepatic, via CYP2C8 and CYP3A4	Potential for drug-drug interactions with inhibitors/inducers of these enzymes.	1
Primary Excretion Route	Biliary / Fecal	Not eliminated via the kidneys, making it a potentially safer option in patients with renal impairment.	1

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Section 2: Clinical Development and Efficacy Analysis

This section critically evaluates the body of clinical evidence supporting Saroglitazar's use, examining data from its established indications in diabetic dyslipidemia and NAFLD/NASH, and exploring its potential in promising investigational frontiers.

[2.1. Diabetic Dyslipidemia]

The initial and foundational indication for Saroglitazar is the treatment of diabetic dyslipidemia, a condition characterized by high triglycerides, low HDL cholesterol, and often elevated levels of small, dense LDL particles in patients with type 2 diabetes.[24] The efficacy of Saroglitazar in this population was established through a series of robust clinical trials, most notably the PRESS (Prospective Randomized Efficacy and Safety of Saroglitazar) program.

The pivotal PRESS V study was a 26-week, multicenter, randomized, double-blind, Phase 3 trial that provided a direct head-to-head comparison of Saroglitazar (at 2 mg and 4 mg daily doses) against an active comparator, pioglitazone 45 mg, a well-established PPAR-γ agonist.[17] The results were definitive in establishing Saroglitazar's superior lipid-modifying effects:

• Primary Endpoint (Triglyceride Reduction): At week 24, Saroglitazar 4 mg demonstrated a 45% mean reduction in serum triglycerides from baseline. This was significantly greater than the 15.5% reduction observed in the pioglitazone group (p<.001).[17] The maximum effect on triglycerides was achieved by week 12 and was sustained for the duration of the study.
• Secondary Lipid Endpoints: The superiority of Saroglitazar 4 mg extended to other key atherogenic lipids. It produced marked decreases in VLDL-cholesterol (45.5%), total cholesterol (7.7%), and LDL-cholesterol (5%). In stark contrast, treatment with pioglitazone was associated with increases in both total cholesterol and LDL-cholesterol, highlighting a significant point of differentiation.[17]
• Glycemic Control: Both Saroglitazar and pioglitazone demonstrated comparable efficacy in improving glycemic control, with similar reductions in fasting plasma glucose (FPG) and HbA1c at the end of the 24-week treatment period.[17]

The design and outcome of the PRESS V trial were strategically important. By choosing an active comparator like pioglitazone, the study did more than simply prove efficacy against placebo; it positioned Saroglitazar as a mechanistically superior agent for the specific condition of diabetic dyslipidemia. The data clearly showed that while both drugs effectively address the "diabetic" component (glycemic control), Saroglitazar is far more effective at treating the "dyslipidemia" component. The fact that it improves the overall lipid profile while pioglitazone can worsen certain aspects (LDL-C) provides a clear rationale for clinicians to prefer Saroglitazar in patients where comprehensive metabolic control is the primary goal.

The long-term efficacy and safety of Saroglitazar have been supported by post-marketing and observational data. A 52-week retrospective study involving patients with diabetic dyslipidemia and very high baseline triglycerides (> 500 mg/dL) found that treatment with Saroglitazar 4 mg led to sustained and statistically significant reductions in triglycerides, LDL-cholesterol, and HbA1c over the entire year, confirming its durability in a real-world setting.[19]

[2.2. Non-Alcoholic Fatty Liver Disease (NAFLD) and Steatohepatitis (NASH)]

Building on its potent effects on lipid metabolism and insulin resistance—the core drivers of NAFLD—Saroglitazar's indication was expanded in India to include the treatment of NAFLD and its more severe, inflammatory form, NASH.[4] This expansion was supported by compelling data from the EVIDENCES clinical trial program, which has evaluated the drug in both Indian and U.S. patient populations.

The EVIDENCES IV trial was a landmark study for the program. It was a 16-week, randomized, double-blind, placebo-controlled Phase 2 study conducted at 20 sites in the United States, enrolling 106 patients with NAFLD/NASH.[27] The trial successfully met its primary and key secondary endpoints:

• Primary Endpoint (ALT Reduction): The primary endpoint was the percentage change in serum alanine aminotransferase (ALT), a key marker of liver inflammation. Saroglitazar 4 mg resulted in a statistically significant mean reduction in ALT of 45.8% from baseline. This was in sharp contrast to the placebo group, which saw a 3.4% increase (p<.001).[29]
• Liver Fat Content (MRI-PDFF): A critical secondary endpoint was the change in liver fat content (LFC), measured non-invasively using the gold-standard MRI-Proton Density Fat Fraction (MRI-PDFF). Patients receiving Saroglitazar 4 mg experienced a mean relative reduction in LFC of 19.7%, while the placebo group had a 4.1% increase, a highly significant difference.[29]
• Metabolic Parameters: The trial also confirmed Saroglitazar's effects on the underlying metabolic dysfunction. The 4 mg dose led to significant improvements in insulin resistance (as measured by HOMA-IR), atherogenic dyslipidemia (a 68.7 mg/dL reduction in triglycerides vs. 5.3 mg/dL for placebo), and adiponectin levels compared to placebo.[29] Furthermore, advanced analysis showed that Saroglitazar reduced circulating levels of lipotoxic lipid species, molecules believed to directly drive liver cell injury and inflammation.[29]

These results from EVIDENCES IV are particularly compelling because they demonstrate that Saroglitazar impacts multiple facets of NASH pathophysiology. It does not simply lower liver enzymes; it directly reduces hepatic steatosis (the "fatty liver"), corrects the systemic insulin resistance and dyslipidemia that fuel the disease, and may mitigate the lipotoxicity that causes progression to inflammation and fibrosis. This mechanistic breadth suggests a true disease-modifying potential in a therapeutic area with a significant unmet need and no currently approved therapies.

The development program continues to build on this foundation. Phase 3 trials in India have demonstrated efficacy in both biopsy-proven NASH (showing a significant improvement in the NAFLD Activity Score) and in NAFLD (showing a reduction in LFC by MRI).[31] To generate crucial long-term, real-world data, a large Phase 4 registry study, EVIDENCES-XI (NCT05872269), is currently enrolling 1500 NAFLD patients with comorbidities in India.[31]

Table 2: Key Efficacy Outcomes from Pivotal Clinical Trials

Trial Name	Indication	Comparator	Endpoint	Saroglitazar 4 mg Result	Comparator Result	P-value	Source(s)
PRESS V	Diabetic Dyslipidemia	Pioglitazone 45 mg	% Change in Triglycerides	-45.0%	-15.5%	< 0.001	17
			% Change in LDL-C	-5.0%	+3.5% (increase)	Statistically Superior	17
			Change in HbA1c	-0.3%	-0.4%	Comparable	17
EVIDENCES IV	NAFLD / NASH	Placebo	% Change in ALT	-45.8%	+3.4% (increase)	< 0.001	29
			% Change in Liver Fat Content (MRI-PDFF)	-19.7%	+4.1% (increase)	< 0.05	29
			Change in Triglycerides (mg/dL)	-68.7 mg/dL	-5.3 mg/dL	< 0.05	29

[2.3. Investigational Frontiers: Primary Biliary Cholangitis (PBC) and Beyond]

While Saroglitazar has established a strong foothold in India for metabolic diseases, its sponsor, Zydus, is pursuing a highly strategic approach for entry into Western markets. Rather than immediately seeking approval for the broad and highly competitive indications of diabetes or NASH, the company has focused on securing orphan drug designations for rarer conditions, with Primary Biliary Cholangitis (PBC) as the lead candidate.

PBC is a chronic, autoimmune cholestatic liver disease characterized by the progressive destruction of small bile ducts, leading to cholestasis, fibrosis, and eventual liver failure.[33] The therapeutic rationale for using a PPAR agonist in PBC is based on the role these receptors play in regulating bile acid synthesis and transport, which is expected to reduce bile acid levels and mitigate the resulting liver damage.[35]

This strategic pivot to an orphan indication has been validated by major regulatory agencies:

• U.S. FDA: Saroglitazar received Fast Track Designation for PBC in December 2020, a program designed to expedite the review of drugs for serious conditions with unmet needs. This was followed by the granting of Orphan Drug Designation in January 2021.[33]
• European Medicines Agency (EMA): The EMA also granted Saroglitazar Orphan Drug Designation for the treatment of PBC in July 2021.[34]

This approach is a shrewd regulatory and commercial maneuver. Developing a drug for a large indication like NASH in the U.S. or E.U. requires massive, long, and prohibitively expensive clinical trials, often including cardiovascular outcome studies. By targeting a rare disease like PBC, Zydus can conduct smaller, faster, and more focused trials. The orphan drug and fast track designations provide significant benefits, including tax credits, user fee exemptions, enhanced regulatory support, and, most importantly, a period of market exclusivity upon approval.[33] This strategy effectively de-risks the company's global expansion, allowing it to establish a commercial foothold and build credibility with Western regulators using a high-value asset. This initial approval can then serve as a foundation from which to pursue label expansions into larger indications in the future. Clinical development in PBC is advanced, with results from the Phase 2 EPICS trial having been presented and a Phase 2/3 trial (NCT05133336) now completed.[23]

The development pipeline for Saroglitazar remains active in other areas as well, including severe hypertriglyceridemia (a Phase 2 trial was planned in the U.S.), other cholestatic liver diseases, and niche populations such as NAFLD in people living with HIV (a trial for which has been completed).[2]

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Section 3: Safety, Tolerability, and Risk Management

This section provides a balanced assessment of Saroglitazar's safety profile, integrating data from across its extensive clinical program to identify patterns, address specific areas of concern, and outline necessary risk management and monitoring strategies.

[3.1. Comprehensive Safety Profile from Clinical Trials]

Across a multitude of clinical trials, post-marketing surveillance in India, and formal meta-analyses, Saroglitazar has consistently demonstrated a favorable safety and tolerability profile.[4] No major or unexpected serious adverse events have been consistently attributed to the drug.[1] The most commonly reported adverse events are generally mild to moderate in nature and transient. These include gastrointestinal symptoms like gastritis and dyspepsia, as well as systemic effects such as asthenia (lack of energy or weakness), pyrexia (fever), headache, and dizziness.[4]

The robustness of this safety conclusion is strengthened by a systematic review and meta-analysis published in 2022. This analysis pooled data from six interventional studies involving 581 patients and concluded that Saroglitazar appeared to be an effective and safer therapeutic option for the management of dyslipidemia.[16] The consistency of the "safe and well-tolerated" finding across numerous independent studies and a formal pooled analysis provides a high degree of confidence in the general safety of Saroglitazar, at least for short- to medium-term use in its target populations. The absence of new, alarming safety signals upon data aggregation suggests that the observed adverse events are likely infrequent and not of severe clinical concern, solidifying a positive risk-benefit assessment for its approved indications.

[3.2. Key Safety Considerations and Monitoring]

Despite its overall favorable profile, a comprehensive risk assessment requires a closer examination of specific safety topics that have emerged from clinical data or are relevant to its drug class.

• Serum Creatinine: The most notable and ambiguous safety finding for Saroglitazar relates to its effect on serum creatinine. A mild but statistically significant increase in serum creatinine was initially noted in a meta-analysis and subsequently observed in a randomized controlled trial with the 4 mg dose at 16 weeks.[1] This finding has raised some concern. However, the data is not entirely consistent. A long-term, 52-week observational study reported that creatinine levels did not alter significantly over the course of treatment.[26] Furthermore, in a direct head-to-head comparison with fenofibrate, Saroglitazar treatment resulted in no significant change in creatinine, whereas fenofibrate led to a significant increase, highlighting a relative safety advantage.[8] This conflicting evidence represents the most significant unresolved question in Saroglitazar's safety profile. While its non-renal pharmacokinetic pathway is reassuring, the observed elevations in some studies warrant further investigation. It is crucial to determine whether this is a benign hemodynamic effect (e.g., an alteration in creatinine secretion without a change in glomerular filtration rate, a phenomenon seen with some other metabolic drugs) or an early indicator of subclinical renal toxicity. The resolution of this issue, likely to be informed by the completed study in patients with renal impairment (NCT04446507), is critical for its long-term positioning against competitors like fibrates, where renal safety is a known and more pronounced concern.[23]
• Weight Gain and Edema: One of Saroglitazar's clearest safety advantages is the consistent absence of weight gain and peripheral edema.[5] These are hallmark adverse effects of potent PPAR-γ agonists, including the thiazolidinediones. The PRESS V trial provided direct evidence of this benefit, where patients in the pioglitazone arm experienced a mean weight gain of 1.6 kg and reports of peripheral edema, while no such effects were observed in the Saroglitazar arms.[17] This distinction is a major clinical benefit, particularly in patients with diabetes, obesity, or heart failure, where fluid retention and weight gain are highly undesirable.
• Liver Function: As Saroglitazar is extensively metabolized by the liver and is also indicated for the treatment of liver diseases like NAFLD, monitoring of liver function tests is a standard and prudent measure.[11] However, clinical studies have been reassuring in this regard. Data from multiple trials have shown either no significant alteration or an actual improvement in liver enzymes (such as ALT and AST) with Saroglitazar treatment.[10] In the EVIDENCES IV trial, it led to a significant reduction in ALT in patients with NAFLD/NASH.[29]
• Cardiovascular Safety: A critical remaining gap in the evidence base is the lack of long-term cardiovascular safety data from a dedicated cardiovascular outcomes trial (CVOT).[1] While its effects on multiple cardiovascular risk factors (lipids, glucose, insulin resistance) are favorable, and no cardiac safety signals have emerged in shorter-term trials, definitive evidence of its long-term impact on cardiovascular events like myocardial infarction and stroke is not yet available. Such trials are now a standard regulatory expectation for new metabolic drugs in many parts of the world and will likely be necessary for broad approval in major Western markets.

[3.3. Clinically Relevant Drug-Drug Interactions]

Saroglitazar's metabolic profile necessitates careful consideration of potential drug-drug interactions, particularly given that its target patient population is often on polypharmacy for comorbid conditions.

• CYP450-Mediated Interactions: Saroglitazar is primarily metabolized by the hepatic enzymes CYP2C8 and CYP3A4.[1] Co-administration with drugs that are strong inhibitors of these enzymes could lead to increased plasma concentrations of Saroglitazar and a higher risk of adverse effects. Conversely, co-administration with strong inducers could decrease its concentration and reduce its efficacy. The CYP2C8 pathway is a notable liability, as several commonly prescribed medications are inhibitors (e.g., gemfibrozil) or substrates (e.g., some oral antidiabetics). The clinical trial protocol for the EVIDENCES VI study explicitly lists the use of CYP2C8 inhibitors as an exclusion criterion, indicating that the sponsor considers this interaction to be clinically significant.[43] Prescribers must conduct a thorough medication review to avoid these potential interactions.
• Interactions with Other Metabolic Drugs:
• Antidiabetic Medications: When used in combination with other glucose-lowering agents such as metformin, sulfonylureas, or insulin, there is an additive effect that increases the risk of hypoglycemia. Close monitoring of blood glucose levels is essential, and dosage adjustments of the concomitant antidiabetic medications may be required.[20]
• Lipid-Lowering Medications: While often used in patients already on statins, the combined use should be monitored for any signs of potential liver toxicity.[11] The combination of Saroglitazar with other PPAR agonists, such as fibrates or thiazolidinediones, is generally not recommended due to an increased risk of class-specific side effects and overlapping mechanisms of action.[11]
• Anticoagulants: There is a potential for interaction with anticoagulants like warfarin. Therefore, regular monitoring of blood clotting parameters, such as the International Normalized Ratio (INR), is recommended when initiating or adjusting the dose of Saroglitazar in patients on such therapy.[11]

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Section 4: Therapeutic Positioning and Comparative Assessment

This section situates Saroglitazar within the existing therapeutic landscape for metabolic disorders by directly comparing its efficacy and safety profile against the two established classes of drugs it was designed to improve upon: thiazolidinediones (PPAR-γ agonists) and fibrates (PPAR-α agonists).

[4.1. Versus Thiazolidinediones (e.g., Pioglitazone)]

Thiazolidinediones, such as pioglitazone, are potent insulin sensitizers that act primarily through the activation of PPAR-γ. The direct, head-to-head comparison in the PRESS V clinical trial provides the clearest evidence for Saroglitazar's therapeutic position relative to this class in the context of diabetic dyslipidemia.[17]

• Comparative Efficacy: The trial revealed a clear divergence in efficacy profiles. While both Saroglitazar and pioglitazone demonstrated comparable and effective glycemic control (lowering FPG and HbA1c), their effects on the lipid profile were markedly different. Saroglitazar proved significantly more effective at lowering triglycerides and other atherogenic lipids, such as VLDL and total cholesterol. Critically, pioglitazone was associated with an increase in LDL-cholesterol, an undesirable effect in patients at high cardiovascular risk, whereas Saroglitazar produced a modest reduction.[17]
• Comparative Safety: The safety comparison further favors Saroglitazar. It is devoid of the hallmark TZD adverse effects of weight gain and peripheral edema. In the PRESS V study, these side effects were observed in the pioglitazone arm but were absent in the Saroglitazar arms.[5]

This evidence base allows for a clear conclusion: Saroglitazar represents a significant therapeutic evolution from the TZDs for the specific management of diabetic dyslipidemia. It effectively de-links the beneficial insulin sensitization of PPAR-γ agonism from the adverse effects on weight, fluid retention, and certain atherogenic lipids. For a patient presenting with both hyperglycemia and a high-triglyceride lipid profile, Saroglitazar addresses both pathologies more comprehensively and with a superior safety and tolerability profile than pioglitazone. It offers a more targeted and mechanistically appropriate solution, making it a superior choice for this patient population.

[4.2. Versus Fibrates (e.g., Fenofibrate)]

Fibrates are pure PPAR-α agonists and have long been the standard of care for treating severe hypertriglyceridemia.[8] A randomized, double-blind, active-control trial directly comparing Saroglitazar 4 mg to fenofibrate 160 mg in patients with moderate to severe hypertriglyceridemia provides a robust basis for a comparative assessment.[8]

• Comparative Efficacy: In this head-to-head trial, Saroglitazar was not only non-inferior but was found to be statistically superior to fenofibrate in the primary endpoint of triglyceride reduction at 12 weeks (-55.3% for Saroglitazar vs. -41.1% for fenofibrate; p=0.048). Beyond its primary lipid effect, Saroglitazar conferred the additional benefit of improved glycemic control, showing a significant reduction in FPG and HbA1c, an effect not seen with the pure PPAR-α agonist fenofibrate. It also produced a significantly greater increase in adiponectin levels, reflecting its moderate PPAR-γ activity.[8]
• Comparative Safety: The safety profiles also diverged in clinically meaningful ways. Fenofibrate treatment was associated with a statistically significant increase in serum creatinine (a 10.7% rise) and elevations in liver enzymes (ALT, AST). In contrast, Saroglitazar had no significant effect on creatinine and was associated with reductions in liver enzymes, indicating a more favorable renal and hepatic safety profile.[8]

The results of this comparative trial make a compelling case for Saroglitazar as a potential replacement for fibrates, particularly in the high-risk population of patients who also have diabetes or metabolic syndrome. To displace an established standard of care, a new drug must demonstrate a clear advantage. Saroglitazar demonstrates a trifecta of benefits: superior efficacy in lowering triglycerides, the valuable added benefit of glycemic control, and a superior safety profile with respect to key renal and hepatic markers. This combination of advantages positions Saroglitazar as a more comprehensive and safer therapeutic option than fibrates for managing hypertriglyceridemia in patients with underlying metabolic dysfunction.

Table 3: Comparative Profile of Saroglitazar, Pioglitazone, and Fenofibrate

Feature	Saroglitazar	Pioglitazone (a TZD)	Fenofibrate (a Fibrate)	Source(s)
Mechanism of Action	Dual PPAR-α/γ Agonist (Predominant α)	PPAR-γ Agonist	PPAR-α Agonist	3
Efficacy (Triglycerides)	High (e.g., -45% to -55%)	Modest (e.g., -15.5%)	High (e.g., -41%)	8
Efficacy (Glycemic Control)	Moderate (Improves HbA1c/FPG)	High (Potent insulin sensitizer)	None	8
Key Safety Concern (Weight Gain/Edema)	Not associated	Significant risk	Not associated	7
Key Safety Concern (Serum Creatinine)	Mild, inconsistent increase noted in some studies	Not a primary concern	Significant risk of increase	1
Key Safety Concern (Liver Enzymes)	Associated with improvement	Risk of hepatotoxicity (class effect)	Risk of increase	8

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Section 5: Regulatory Landscape and Future Directions

This section traces Saroglitazar's unique journey from a domestic Indian innovation to a potential global therapy, analyzing its regulatory milestones, challenges, and the ongoing clinical trials that will define its future role in medicine.

[5.1. Global Regulatory Journey]

Saroglitazar's path to market is a landmark story in pharmaceutical development. It was discovered in 2001 and, after more than a decade of development, received marketing authorization from the Drug Controller General of India (DCGI) in June 2013.[6] Marketed under the trade name Lipaglyn, its approval was a historic achievement, marking it as the first New Chemical Entity (NCE) to be discovered and developed entirely by an Indian pharmaceutical company.[6] The initial approval was for the treatment of diabetic dyslipidemia in patients not adequately controlled by statin therapy, an indication that was later expanded to include NAFLD and NASH based on accumulating clinical evidence.[1]

The attempt to bring Saroglitazar to Western markets has been a more complex and evolving process. An early challenge arose in December 2016, when a research subsidiary of Zydus received a letter from the U.S. FDA citing the company for misbranding and making unsubstantiated promotional claims, such as using the term "world's first" and implying that the drug had global approval when it was only approved in India.[1] This event highlighted a significant learning curve in navigating the stringent regulatory and promotional standards of major Western markets.

Following this initial setback, the company adopted a more sophisticated and data-driven regulatory strategy. Instead of pursuing the broad metabolic indications first, Zydus pivoted to focus on the orphan disease Primary Biliary Cholangitis (PBC). This strategic shift has been highly successful in re-engaging with regulators:

• In the United States, the FDA granted Saroglitazar Fast Track Designation in December 2020 and Orphan Drug Designation for PBC in January 2021.[36]
• In Europe, the European Medicines Agency (EMA) followed suit, granting Orphan Drug Designation for PBC in July 2021.[34]

These special designations do not constitute marketing approval but are crucial endorsements that provide significant development incentives and a potentially faster path to market.[33] This regulatory history illustrates the immense challenge for a non-Western company in globalizing an NCE. The initial misstep and subsequent successful pivot demonstrate a maturation of strategy, reflecting a long-term commitment to establishing Saroglitazar as a global product by building a solid regulatory foundation in a niche indication first.

[5.2. The Current Clinical Trial Pipeline]

Saroglitazar's future potential will be defined by its ongoing and planned clinical trials, which are designed to expand its evidence base, secure global approvals, and explore new indications. A review of the ClinicalTrials.gov registry reveals a robust and strategically focused development program.[23]

• Pivotal NASH with Fibrosis Trial: The most critical trial in the current pipeline is NCT05011305. This is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of Saroglitazar in patients with biopsy-proven NASH and significant fibrosis (stages F2-F3). This is a large-scale, 72-week study being conducted primarily in the U.S., with an estimated enrollment of 180 patients. The primary endpoints are based on histological improvement—resolution of NASH or improvement in fibrosis—which are the key endpoints required for regulatory approval in this high-value indication. The estimated study completion date is September 2025.[31] Success in this trial would be transformative, as NASH with fibrosis represents the patient population at the highest risk of progression to cirrhosis and liver failure, and there are currently no approved therapies. It is a high-risk, high-reward endeavor that, if successful, could establish Saroglitazar as a foundational therapy for NASH globally.
• NAFLD Real-World Evidence: In India, the EVIDENCES-XI trial (NCT05872269) is a large-scale Phase 4 open-label registry that is currently recruiting. It aims to enroll 1500 patients with NAFLD and common comorbidities (such as obesity, type 2 diabetes, or dyslipidemia) to evaluate the long-term safety and effectiveness of Saroglitazar in a real-world clinical practice setting. This study will generate invaluable data on the drug's performance outside the rigid confines of a randomized controlled trial.[31]
• Completed Trials of Note: The development program has also completed several other important studies that are informing the drug's profile. These include trials in patients with post-liver transplant NAFLD (NCT03639623), subjects with severe renal impairment (NCT04446507), patients with NAFLD and co-infection with HIV (NCT05211284), and the pivotal trials in PBC (NCT05133336).[23] A trial in patients with severe hypertriglyceridemia (NCT03097107) is currently listed as suspended, indicating a potential shift in development priorities.[23]

[5.3. Expert Synthesis and Concluding Remarks]

Saroglitazar is a molecule born from a deliberate and intelligent design philosophy. It stands as the sole approved agent in the "glitazar" class, a testament to its unique ability to strike a favorable balance between the potent metabolic efficacy of dual PPAR agonism and the safety required for clinical success.[15] Its distinct profile as a dual agonist with predominant PPAR-α activity has been validated in robust clinical trials, where it has demonstrated compelling efficacy in treating the interconnected pathologies of diabetic dyslipidemia and non-alcoholic fatty liver disease.

The clinical evidence strongly suggests that Saroglitazar offers a superior risk-benefit profile compared to older drug classes that target the same metabolic pathways. It provides more comprehensive lipid control than thiazolidinediones without the associated weight gain and edema, and it offers superior triglyceride-lowering and an improved safety profile compared to fibrates, with the added crucial benefit of glycemic control.

Its journey from being the first indigenously developed Indian NCE to a drug holding special regulatory designations from the FDA and EMA is a story of scientific innovation and strategic persistence. The primary hurdles that remain on its path to becoming a global blockbuster are the generation of definitive long-term cardiovascular safety data through a dedicated outcomes trial and, most critically, the successful execution of its pivotal, biopsy-driven trial in NASH with fibrosis.

If these formidable challenges are met, Saroglitazar has the clear potential to evolve from a national success story into a global standard-of-care therapy. It is well-positioned to address the significant and growing unmet medical needs in NASH, diabetic dyslipidemia, and potentially other related metabolic and hepatic diseases, representing a landmark achievement in pharmaceutical innovation.

Works cited

1. Saroglitazar - Wikipedia, accessed August 27, 2025, https://en.wikipedia.org/wiki/Saroglitazar
2. Saroglitazar: Uses, Interactions, Mechanism of Action | DrugBank ..., accessed August 27, 2025, https://go.drugbank.com/drugs/DB13115
3. Saroglitazar, a novel PPARα/γ agonist with predominant PPARα activity, shows lipid-lowering and insulin-sensitizing effects in preclinical models - PMC - PubMed Central, accessed August 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4492752/
4. Saroglitazar uses, doses, side effects, and precautions - Yashoda Hospital, accessed August 27, 2025, https://www.yashodahospitals.com/medicine-faqs/saroglitazar/
5. e Mechanism of action of saroglitazar. | Download Scientific Diagram - ResearchGate, accessed August 27, 2025, https://www.researchgate.net/figure/e-Mechanism-of-action-of-saroglitazar_fig1_274261419
6. From 'Make in India' to 'Made in India': The saroglitazar story - PMC, accessed August 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4382552/
7. Efficacy and safety of saroglitazar for the management of dyslipidemia, accessed August 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9249226/
8. Saroglitazar is noninferior to fenofibrate in reducing triglyceride ..., accessed August 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9240860/
9. Saroglitazar for the treatment of dyslipidemia in diabetic patients - ResearchGate, accessed August 27, 2025, https://www.researchgate.net/publication/272187880_Saroglitazar_for_the_treatment_of_dyslipidemia_in_diabetic_patients
10. Observational study to evaluate the safety and efficacy of saroglitazar in Indian diabetic dyslipidemia patients, accessed August 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4382542/
11. What is Saroglitazar used for? - Patsnap Synapse, accessed August 27, 2025, https://synapse.patsnap.com/article/what-is-saroglitazar-used-for
12. What is the mechanism of Saroglitazar? - Patsnap Synapse, accessed August 27, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-saroglitazar
13. Pharmacokinetics, safety, and tolerability of saroglitazar (ZYH1), a predominantly PPARα agonist with moderate PPARγ agonist activity in healthy human subjects - PubMed, accessed August 27, 2025, https://pubmed.ncbi.nlm.nih.gov/24062180/
14. Exploring the Safety and Effectiveness of Saroglitazar Superior to Other Drugs in the Management of Diabetic Dyslipidemia, accessed August 27, 2025, https://www.johp.journalofhospitalpharmacy.in/admin/freePDF/h46ufh0p9x323a7595eg.pdf
15. The First Approved Agent in the Glitazar's Class: Saroglitazar | Request PDF - ResearchGate, accessed August 27, 2025, https://www.researchgate.net/publication/254263253_The_First_Approved_Agent_in_the_Glitazar's_Class_Saroglitazar
16. Efficacy and safety of saroglitazar for the management of dyslipidemia: A systematic review and meta-analysis of interventional studies | PLOS One - Research journals, accessed August 27, 2025, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269531
17. A Multicenter, Prospective, Randomized, Double-blind Study to ..., accessed August 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4390522/
18. Zydus announces clinical trials of Saroglitazar in patients with Severe Hypertriglyceridemia in USA - FirstWord Pharma, accessed August 27, 2025, https://firstwordpharma.com/story/3263386
19. Long Term Safety and Efficacy of Saroglitazar in Indian Patients with Diabetic Dyslipidemia and Very High Triglyceride Levels: Real World Evidence | Baidya | Clinical Diabetology - Via Medica Journals, accessed August 27, 2025, https://journals.viamedica.pl/clinical_diabetology/article/view/76311
20. Saroglitazar: Uses, Side Effects, Precautions and More - CARE Hospitals, accessed August 27, 2025, https://www.carehospitals.com/medicine-detail/saroglitazar
21. Pharmacokinetics, Safety, and Tolerability of Saroglitazar (ZYH1), a ..., accessed August 27, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC3824340/
22. Pharmacokinetics, Safety, and Tolerability of Saroglitazar (ZYH1), a Predominantly PPARα Agonist with Moderate PPARγ Agonist Activity in Healthy Human Subjects - ResearchGate, accessed August 27, 2025, https://www.researchgate.net/publication/256985254_Pharmacokinetics_Safety_and_Tolerability_of_Saroglitazar_ZYH1_a_Predominantly_PPARa_Agonist_with_Moderate_PPARg_Agonist_Activity_in_Healthy_Human_Subjects
23. Search for: Saroglitazar | Card Results | ClinicalTrials.gov, accessed August 27, 2025, https://www.clinicaltrials.gov/ct2/results?cond=&term=&type=&rslt=&age_v=&gndr=&intr=Saroglitazar+&titles=&outc=&spons=&lead=&id=&cntry=&state=&city=&dist=&locn=&rsub=&strd_s=&strd_e=&prcd_s=&prcd_e=&sfpd_s=&sfpd_e=&rfpd_s=&rfpd_e=&lupd_s=&lupd_e=&sort=
24. en.wikipedia.org, accessed August 27, 2025, https://en.wikipedia.org/wiki/Saroglitazar#:~:text=Saroglitazar%20is%20indicated%20for%20the,not%20controlled%20by%20statin%20therapy.
25. (PDF) A Multicenter, Prospective, Randomized, Double-blind Study ..., accessed August 27, 2025, https://www.researchgate.net/publication/262776484_A_Multicenter_Prospective_Randomized_Double-blind_Study_to_Evaluate_the_Safety_and_Efficacy_of_Saroglitazar_2_and_4_mg_Compared_to_Pioglitazone_45_mg_in_Diabetic_Dyslipidemia_PRESS_V
26. Long Term Safety and Efficacy of Saroglitazar in Indian Patients with Diabetic Dyslipidemia and Very High Triglyceride Levels: Real World Evidence | Baidya | Clinical Diabetology - Via Medica Journals, accessed August 27, 2025, https://journals.viamedica.pl/clinical_diabetology/article/view/DK.a2022.0039
27. Zydus Announces Positive Results From EVIDENCES IV Phase 2 Clinical Trial of Saroglitazar Magnesium in NAFLD and NASH - NATAP, accessed August 27, 2025, https://www.natap.org/2019/AASLD/AASLD_82.htm
28. Study Details | Saroglitazar Magnesium in Patients With Nonalcoholic Fatty Liver Disease and/or Nonalcoholic Steatohepatitis | ClinicalTrials.gov, accessed August 27, 2025, https://clinicaltrials.gov/study/NCT03061721
29. Saroglitazar, a PPAR-α/γ Agonist, for Treatment of NAFLD: A ..., accessed August 27, 2025, https://pubmed.ncbi.nlm.nih.gov/33811367/
30. Saroglitazar, a PPAR- α/γ Agonist, for Treatment of NAFLD: A Randomized Controlled Double - NATAP, accessed August 27, 2025, https://www.natap.org/2023/HCV/Saroglitazar_a_PPAR_____Agonist,_for_Treatment_of.9.pdf
31. Zydus announces Phase IV EVIDENCES-XI trial to generate Real World Evidence of Saroglitazar Mg in Non-Alcoholic Fatty Liver Dise, accessed August 27, 2025, https://zyduslife.com/investor/admin/uploads/21/83/Zydus-announces-Phase-IV-EVIDENCES-XI-trial-to-generate-Real-World-Evidence-of-Saroglitazar-Mg-in-Non-Alcoholic-Fatty-Liver-Disease-(NAFLD)-patients-with-comorbidities.pdf
32. A Study to Evaluate the Safety and Effectiveness of Saroglitazar 4 mg in Patients With NAFLD With Comorbidities | ClinicalTrials.gov, accessed August 27, 2025, https://clinicaltrials.gov/study/NCT05872269
33. Zydus granted Orphan Drug Designation by the USFDA for Saroglitazar in the treatment of patients with Primary Biliary Cholangitis (PBC), accessed August 27, 2025, https://www.zyduslife.com/public/pdf/pressrelease/Press_Release_Zydus_granted_Orphan_Drug_Designation_by_the_USFDA_for_Saroglitazar_in_the_treatment_of_patients_with_Primary_Biliary_Cholangitis%20(PBC).pdf
34. European Medicines Agency grants Orphan Drug Designation to Saroglitazar Mg for the treatment of patients with Primary Biliary Cholangitis (PBC), accessed August 27, 2025, https://www.zyduslife.com/public/pdf/pressrelease/European_Medicines_Agency_grants_Orphan_Drug_Designation_to_Saroglitazar_Mg_for_the_treatment_of_patients_with_PBC.pdf
35. EU/3/21/2460 - orphan designation for treatment of primary biliary cholangitis | European Medicines Agency (EMA), accessed August 27, 2025, https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-21-2460
36. Search Orphan Drug Designations and Approvals - FDA, accessed August 27, 2025, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=686819
37. Zydus granted Fast Track Designation by the USFDA for Saroglitazar in the treatment of patients with Primary Biliary Cholangitis (PBC), accessed August 27, 2025, https://www.zyduslife.com/public/pdf/pressrelease/Zydus_granted_Fast_Track_Designation_by_the_USFDA_for_Saroglitazar_in_the_treatment_of_patients_with_PBC.pdf
38. Zydus -Saroglitazar -FDA fast track designation for PBC - Canadian PBC Society, accessed August 27, 2025, https://pbc-society.ca/saroglitazar-fda-fast-track-designation-for-pbc/
39. EMA grants ODD to Saroglitazar Mg - Indian Pharma Post, accessed August 27, 2025, https://www.indianpharmapost.com/news/ema-grants-odd-to-saroglitazar-mg-9715
40. Saroglitazar for PBC Granted Orphan Drug Status in EU - Patient Worthy, accessed August 27, 2025, https://patientworthy.com/2021/07/26/saroglitazar-pbc-granted-eu-orphan-drug-designation/
41. Saroglitazar Magnesium 4 mg for Nonalcoholic Fatty Liver Disease (NAFLD) in People Living With HIV in the US (SARONAPLUS) - ClinicalTrials.gov, accessed August 27, 2025, https://clinicaltrials.gov/study/NCT05211284
42. Saroglitazar | New Drug Approvals, accessed August 27, 2025, https://newdrugapprovals.org/tag/saroglitazar/
43. Study Details | Saroglitazar Magnesium in the Treatment of Non-Alcoholic Steatohepatitis | ClinicalTrials.gov, accessed August 27, 2025, https://clinicaltrials.gov/study/NCT03863574
44. The first approved agent in the Glitazar's Class: Saroglitazar - PubMed, accessed August 27, 2025, https://pubmed.ncbi.nlm.nih.gov/23906191/
45. Study Details | Saroglitazar Magnesium for the Treatment of Nonalcoholic Steatohepatitis with Fibrosis | ClinicalTrials.gov, accessed August 27, 2025, https://clinicaltrials.gov/study/NCT05011305