Sipoglitazar

{{Drugbox | Verifiedfields = changed | verifiedrevid = 477241123 | IUPAC_name = (2S)-2-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenoxy]methyl]-3-methylbutanoic acid | image = Sipoglitazar.svg | width = 250 | CAS_number = 245105-44-8 | ATC_prefix = none | PubChem = 6918495 | ChemSpiderID = 5293663 | UNII = 0T3Z5K0M5K | KEGG = D08895 | ChEMBL = 2103870 | C=21 | H=25 | N=1 | O=4 | smiles = CCC1=CN=C(C=C1)CCOC2=CC=C(C=C2)OCC(C)C(C)C(=O)O | StdInChI = 1S/C21H25NO4/c1-4-18-10-11-19(22-12-18)9-13-25-17-8-6-16(7-5-17)26-14-15(2)20(3)21(23)24/h5-8,10-12,15,20H,4,9,13-14H2,1-3H3,(H,23,24) | StdInChIKey = ZQXKQXQKXJQZQK-UHFFFAOYSA-N }}

Sipoglitazar is a pharmaceutical compound that was investigated for its potential use in the treatment of type 2 diabetes mellitus. It is a member of the class of drugs known as thiazolidinediones, which are used to improve insulin sensitivity in patients with diabetes.

Mechanism of Action

Sipoglitazar is a dual peroxisome proliferator-activated receptor (PPAR) agonist, specifically targeting both the PPAR-alpha and PPAR-gamma receptors. These receptors are nuclear hormone receptors that regulate the expression of genes involved in glucose and lipid metabolism.

• PPAR-alpha activation: This leads to increased fatty acid oxidation and improved lipid profiles, which can be beneficial in reducing cardiovascular risk factors associated with diabetes.
• PPAR-gamma activation: This enhances insulin sensitivity by promoting the uptake of glucose in adipose tissue and muscle, thereby lowering blood glucose levels.

Clinical Development

Sipoglitazar was developed by Takeda Pharmaceutical Company and underwent clinical trials to evaluate its efficacy and safety in patients with type 2 diabetes. However, like many drugs in its class, concerns about potential side effects, such as cardiovascular disease and weight gain, led to challenges in its development.

Side Effects and Safety

The side effects associated with thiazolidinediones, including sipoglitazar, can include:

• Weight gain
• Edema (fluid retention)
• Increased risk of heart failure
• Potential bone fractures

Due to these concerns, the development of sipoglitazar was eventually discontinued.

Research and Future Directions

While sipoglitazar itself is no longer being developed, research into dual PPAR agonists continues, as they hold promise for addressing both glucose and lipid abnormalities in diabetes. Future compounds may aim to retain the beneficial effects while minimizing adverse outcomes.

Also see

• Thiazolidinedione
• Type 2 diabetes mellitus
• Peroxisome proliferator-activated receptor
• Insulin resistance