Saroglitazar is a medication developed by the Indian pharmaceutical company Zydus Cadila. It is a new chemical entity designed to address certain metabolic disorders. The drug is marketed under the trade names Lipaglyn and Bilypsa.
Conditions It Addresses
Saroglitazar is approved to treat specific metabolic conditions, primarily diabetic dyslipidemia and non-alcoholic fatty liver disease (NAFLD), including its more severe form, non-alcoholic steatohepatitis (NASH). Diabetic dyslipidemia refers to abnormal blood lipid levels often seen in individuals with type 2 diabetes, characterized by high triglycerides, low “good” cholesterol (HDL), and high “bad” cholesterol (LDL). This imbalance contributes to an increased risk of cardiovascular disease.
Non-alcoholic fatty liver disease (NAFLD) involves the accumulation of excessive fat in liver cells, unrelated to alcohol consumption. If left unmanaged, NAFLD can progress to NASH, where liver fat is accompanied by inflammation and liver cell damage, potentially leading to fibrosis, cirrhosis, and liver failure. Saroglitazar addresses these conditions by improving lipid profiles and liver parameters.
Mechanism of Action
Saroglitazar operates through a unique dual mechanism, acting as an agonist for both peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ). PPARs are nuclear receptors that regulate the expression of genes involved in various metabolic processes, including lipid and glucose metabolism.
Activation of PPARα primarily influences lipid metabolism. This action leads to increased beta-oxidation of fatty acids in the liver, which reduces triglycerides and very low-density lipoprotein (VLDL) cholesterol.
Concurrently, PPARγ agonism primarily affects glucose metabolism. Activation of PPARγ enhances insulin sensitivity by modulating genes involved in glucose uptake and utilization. It also promotes the storage of free fatty acids in adipose tissue, rather than in other organs like the liver and muscles, which helps reduce insulin resistance. This combined action allows saroglitazar to simultaneously manage lipid abnormalities and improve insulin sensitivity.
Patient Outcomes and Side Effects
Saroglitazar effectively lowers high blood triglycerides, very low-density lipoprotein (VLDL) cholesterol, and low-density lipoprotein (LDL) cholesterol, while also increasing high-density lipoprotein (HDL) cholesterol. This improvement in lipid parameters is particularly beneficial for individuals with diabetic dyslipidemia, reducing cardiovascular risk. The drug also helps control blood sugar levels by reducing fasting plasma glucose and HbA1c in diabetes patients.
For individuals with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), saroglitazar has demonstrated promising results. It can reduce liver fat content, decrease inflammation, and improve markers of liver damage. Some studies also indicate potential for reducing liver fibrosis progression, though further research is ongoing to fully establish this benefit. A mild decrease in body weight, typically ranging from 1.5 to 3 kg over six months, has also been observed in some patients.
Saroglitazar can cause side effects. Common mild effects include gastrointestinal disturbances (nausea, vomiting, diarrhea, abdominal pain), headache, dizziness, weakness, fever, stomach inflammation, and chest pain. These are usually temporary and manageable.
More serious, though less common, side effects include liver function abnormalities, indicated by elevated liver enzymes, necessitating regular monitoring. Muscle-related side effects, such as myalgia (muscle pain) or muscle weakness, have been reported, and in rare cases, more severe conditions like myopathy or rhabdomyolysis. Saroglitazar does not cause hypoglycemia, but it may occur if used with other diabetes medications like sulfonylureas or insulin, which may require dose adjustments. Allergic reactions, though uncommon, can manifest as rash, itching, swelling, or difficulty breathing, requiring immediate medical attention.
Global Availability
Saroglitazar is primarily approved and available in India. The Drug Controller General of India (DCGI) cleared it for the treatment of diabetic dyslipidemia and hypertriglyceridemia in type 2 diabetes mellitus in June 2013. In March 2020, the DCGI also approved saroglitazar for the treatment of non-cirrhotic NASH in India.
Currently, no U.S. Food and Drug Administration (FDA) approved medications exist for NASH, and saroglitazar has not received FDA approval. Its regulatory status in other regions is under investigation. Clinical trials continue to explore its efficacy and safety for broader indications.