Is Saroglitazar (PPAR gamma agonist) useful in the management of acanthosis nigricans?

Saroglitazar in the Management of Acanthosis Nigricans

Saroglitazar is not specifically recommended for the management of acanthosis nigricans (AN) according to current guidelines, as there is insufficient evidence supporting its use for this condition. 1

Understanding Acanthosis Nigricans

• Acanthosis nigricans is a skin condition characterized by velvety, hyperpigmented, hyperkeratotic plaques commonly found on intertriginous areas such as the neck, axilla, and groin 2
• AN is strongly associated with insulin resistance, obesity, diabetes mellitus, and other endocrine disorders 3
• The condition serves as an important clinical marker for metabolic disorders, particularly in children and adolescents, where it can be an early indicator of insulin resistance and risk for type 2 diabetes 1

Primary Management Approaches

Weight Reduction - First-Line Approach

• Weight reduction is considered the most effective strategy for obesity-associated acanthosis nigricans 1
• A target of 7-10% decrease in excess weight is recommended for obese patients with AN 1
• This approach addresses the underlying insulin resistance that contributes to the development of AN 2

Treatment of Underlying Conditions

• Management should focus on identifying and treating underlying endocrinopathies such as PCOS 1
• Screening for type 2 diabetes with fasting glucose and a two-hour glucose tolerance test is recommended 1
• Additional testing should include thyroid function tests and lipid panels to evaluate for other metabolic disorders 1

Pharmacological Options for AN

Insulin Sensitizers

• Metformin has been studied for AN treatment with modest improvements in skin texture reported, though efficacy on AN lesions was limited in short-term studies 4
• Rosiglitazone (a PPAR-γ agonist similar to saroglitazar) showed significant reduction in insulin levels in small studies, but only modest improvement in skin texture 4
• Longer treatment periods with insulin sensitizers might be necessary to observe significant improvement in AN 4, 5

Saroglitazar's Potential Mechanism

• Saroglitazar is a dual PPAR-α/γ agonist with effects on lipid metabolism and insulin sensitivity 6
• It modulates adhesion molecule expression and provides anti-inflammatory effects through PPAR-α/γ-mediated mechanisms 6
• While these mechanisms could theoretically benefit AN by improving insulin sensitivity, there is no direct evidence supporting its use specifically for AN 6

Clinical Considerations

Relationship Between AN and Hepatic Disease

• Recent research indicates that AN independently predicts hepatic fibrosis in people with type 2 diabetes 7
• Saroglitazar has been studied for non-alcoholic fatty liver disease (NAFLD) 8, but not specifically for AN
• The American Association for the Study of Liver Diseases notes that thiazolidinediones (PPAR-γ agonists) can improve liver histology in NAFLD 8, but does not mention their use for associated AN

Treatment Limitations

• Complete cure and disappearance of AN lesions are difficult to achieve with any current treatment 2
• Long-term studies on the management of AN are lacking, making it difficult to establish definitive treatment recommendations 2

Practical Approach to AN Management

1. First-line approach: Focus on weight reduction with a target of 7-10% decrease in excess weight 1
2. Address underlying conditions: Screen for and treat diabetes, PCOS, and other endocrinopathies 1
3. Consider insulin sensitizers: Metformin may be tried for its modest effects on AN and underlying insulin resistance 5
4. Monitor for hepatic disease: Given the association between AN and hepatic fibrosis, consider screening for NAFLD 7

While saroglitazar's dual PPAR-α/γ activity might theoretically benefit patients with AN by improving insulin sensitivity and providing anti-inflammatory effects 6, there is currently insufficient evidence to recommend it specifically for AN management.