PPAR α/γ Agonist in Management of Diabetic Dyslipidemia: A Review

Cardiovascular diseases are major contributors of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM), while dyslipidemia and hyperglycemia are key modifiable risk factors to prevent coronary artery disease (CAD). Although healthy diet, regular physical activity and maintaining a normal body weight are advised, patients generally require single or multiple drugs to treat T2DM. Moreover, patients with T2DM are prone to atherogenic diabetic dyslipidemia (ADD), which is characterized by elevated triglyceride, small dense LDL particles and low High-density lipoprotein (HDL) cholesterol. Even though low-density lipoprotein cholesterol (LDL) remains the primary target of therapy, non-high density lipoprotein (non-HDL) cholesterol is as an important parameter to be considered in clinical practice. Unfortunately, high-dose statin therapy is not advised for long term, as it can increase risk of new onset T2DM. On the other hand, glitazars are newer molecules having dual peroxisome proliferator-activated receptors (PPAR) α/γ agonistic action that can improve lipid profile with improvement of insulin sensitivity. In conclusion, the overall safety of saroglitazar is acceptable due to minimal side effects, but improvement of β cell function, effect on insulin sensitivity by analysis of insulin resistance index by using the homeostatic model assessment (HOMAIR) and long term cardiovascular benefits like atherosclerotic plaque stabilization or regression need to be confirmed.