PPAR Gamma Agonist Market: Competitive Landscape, Pipeline, and Market Analysis 2024

Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG), also known as the glitazone reverse insulin resistance receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3) is a type II nuclear receptor functioning as a transcription factor that in humans is encoded by the PPARG gene. PPARG is mainly present in adipose tissue, the colon, and macrophages. Two isoforms of PPARG are detected in humans PPAR-γ1, found in nearly all tissues except muscle, and PPAR-γ2, mostly found in adipose tissue and the intestine. PPARG regulates fatty acid storage and glucose metabolism. Mechanism of action (MOA) of PPAR Gamma agonists involves binding to and activating PPAR gamma receptors. Upon activation, PPAR gamma forms a heterodimer with another nuclear receptor called RXR (retinoid X receptor). This PPAR gamma/RXR complex then binds to specific DNA sequences known as PPAR response elements (PPREs) within the promoter regions of target genes.

Once bound to PPREs, the PPAR gamma/RXR complex recruits co-activator proteins, which facilitate the transcription of target genes. These genes are involved in various metabolic processes, including adipogenesis (formation of new fat cells), lipid metabolism, glucose homeostasis, insulin sensitivity, and inflammation. PPAR Gamma Agonist is used in the treatment of endocrine system diseases, diabetes mellitus, glucose metabolism disorder, acute coronary syndrome, digestive system diseases, hyperinsulinism, heart diseases, hypertension, liver diseases, blood coagulation disorder, brain diseases, etc. The rising prevalence of endocrine diseases, diabetes mellitus, and an aging population are the key drivers for the PPAR Gamma Agonist market. For instance, according to the World Health Organization 2023, About 422 million people worldwide have diabetes. Moreover, the development of novel molecules by many market players is coming up to overcome challenges in therapy. For instance, Roche’s Aleglitazar (R1439) for the treatment of diabetes mellitus is under the various stages of clinical studies.

Key Market Developments:

• In December 2022, according to the Biomedical Journal research findings, Peroxisome proliferator-activated receptor-γ agonist Pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus.

Drugs under the Pipeline for PPAR Gamma Agonist:

• Duvie (Lobeglitazone)
• Aleglitazar (R1439)
• Lipaglyn (Saroglitazar)
• Liovel (Alogliptin/Pioglitazone)
• Avandamet (Rosiglitazone/Metformin)
• Efatutazone (CS-7017)
• Bilessglu (Chiglitazar)
• Arhalofenate (MBX-102)
• Rivoglitazone (CS-011)
• Janacti (Sitagliptin/ Pioglitazone)
• Lanifibranor (IVA337)
• ABTL0812
• Indeglitazar (PLX204)
• EHP-101
• GSK376501
• Leriglitazone (MIN-102)
• Linagliptin/Pioglitazone
• Atx08-001
• T3D-959
• Pioglitazone SR (AD-4833 SR)
• Pioglitazone/Metformin/Dapagliflozin (BR3003)
• Actoplus Met XR (Pioglitazone/Metformin XR)
• Avandaryl (Rosiglitazone/Glimepiride)
• CB-0406
• DSP-8658
• KDT501
• MBX-2044
• Balaglitazone (DRF-2593)

Clinical Activity and Developments of PPAR Gamma Agonist:

Till July 2023, more than 30 companies have approximately 32 molecules targeting the many endocrine disorders and diabetes mellitus. For these molecules, more than 105 clinical trials are being conducted and the majority are in phase-2 and phase-3 clinical trials by the players across the globe. For instance,

• In November 2021, Roche completed the phase 2, randomized, double-blind, study to evaluate the effect of Aleglitazar (R1439) on glycemic control in patients with type 2 diabetes mellitus.
• In June 2023, Daiichi Sankyo completed a phase 2 study of the peroxisome proliferator-activated receptor gamma agonist, Efatutazone (CS-7017) in patients with previously treated, unresectable myxoid liposarcoma.