What class of medication is saroglitazar?

Saroglitazar: A Dual PPAR α/γ Agonist

Saroglitazar is a dual peroxisome proliferator-activated receptor (PPAR) agonist with predominant PPAR-α activity and moderate PPAR-γ activity, primarily used for diabetic dyslipidemia.

Pharmacological Classification

Saroglitazar belongs to a unique class of dual PPAR agonists that combines properties of two established drug classes:

• Primary mechanism: Predominantly PPAR-α agonist (similar to fibrates)
• Secondary mechanism: Moderate PPAR-γ agonist (similar to thiazolidinediones like pioglitazone) 1

This dual mechanism differentiates it from:

• Pure PPAR-α agonists (fibrates like fenofibrate)
• Pure PPAR-γ agonists (thiazolidinediones like pioglitazone)

Pharmacological Effects

The dual PPAR agonist activity of saroglitazar produces several therapeutic effects:

1. PPAR-α effects (predominant):

   • Reduction in triglycerides (45-62%)
   • Reduction in total cholesterol (17-26%)
   • Reduction in non-HDL cholesterol (21-36%)
   • Increase in HDL cholesterol (up to 9%) 1

2. PPAR-γ effects (moderate):

   • Improvement in glycemic parameters
   • Reduction in HbA1c (0.7-1.6%)
   • Improvement in insulin sensitivity 2, 3

Clinical Applications

Saroglitazar is primarily indicated for:

• Diabetic dyslipidemia: Particularly effective for patients with elevated triglycerides 1
• Non-alcoholic fatty liver disease (NAFLD): Improves liver enzymes and reduces fatty liver 1, 4
• Type 2 diabetes with hypertriglyceridemia: Improves both lipid and glycemic parameters 2

Pharmacokinetics

• Absorption: Rapidly absorbed with peak plasma concentration in less than 1 hour
• Half-life: Average terminal half-life of 5.6 hours
• Elimination: Not eliminated via renal route
• Dosing: Supports once-daily dosing schedule 5

Safety Profile

Saroglitazar demonstrates a favorable safety profile:

• Well-tolerated up to doses much higher than therapeutic range (1-4 mg)
• No significant weight gain reported (unlike thiazolidinediones)
• No significant adverse events in studies up to 58 weeks 1, 5
• Minimal side effects reported include pruritus and mild gastrointestinal symptoms in rare cases 4

Comparison to Other PPAR Agonists

Unlike pure PPAR-γ agonists (thiazolidinediones) which carry boxed warnings for heart failure risk 6, saroglitazar's balanced dual action may offer advantages:

• No significant fluid retention or edema reported
• No weight gain observed in clinical studies
• No reported increase in fracture risk 1, 4

Clinical Considerations

When considering saroglitazar:

• Standard dosing is 4 mg once daily
• Monitor lipid parameters and glycemic control
• May be particularly beneficial in patients with combined dyslipidemia and diabetes
• Can improve liver parameters in NAFLD/NASH patients 1, 4

Saroglitazar represents a unique therapeutic option that bridges the gap between lipid-lowering and anti-diabetic medications through its dual PPAR-α/γ agonist mechanism.