Table 2.

Summary of the clinical evidence of PPAR agonists in CVD.

Target	Drug Name	Clinical Phase (Sample Size)	Main Findings/Primary Endpoint	Reference/Clinical Trial Identifier
Dual PPARα/γ	Aleglitazar	III-terminated (7226)	▪ No effect on lowering CVD risk ▪ Induced side effects like gastrointestinal hemorrhages and renal dysfunction	[78]
		III-terminated (1999)	▪ Reduced HbA1c and blood lipids ▪ Increased incidence of hypoglycemia and muscular events	[79]
		II (332)	▪ Lowered HbA1c dose-dependently ▪ Caused edema, hemodilution, and weight gain	[60]
PPARα	Bezafibrate	NA (1568)	▪ Did not reduce incidence of coronary heart disease and stroke ▪ Reduced incidence of non-fatal coronary events	[83]
		NA (3090)	▪ Reduced mortality risk by 10% ▪ Risk reduction was more prominent in patients with hypertriglyceridemia	[84]
		NA (164)	▪ Improved lipid profile ▪ Reduced fibrinogen ▪ No effect on ultrasound measured arterial disease	[85]
		NA (50)	▪ Reduced fibrinogen ▪ Reduced incidence of angina and left ventricular failure	[86]
	Fenofibrate	NA (9795)	▪ Improved lipid profile ▪ Reduced CVD events	[87]
	Gemfibrozil	NA (4081)	▪ Improved lipid profile ▪ Reduced incidence of coronary heart disease	[88]
	Pemafibrate	III (10000)	▪ Primary endpoint: Number of patients with first occurrence of nonfatal MI, nonfatal ischemic stroke, hospitalization for unstable angina requiring unplanned coronary revascularization, or CV death.	NCT03071692
PPARγ	Pioglitazone	IV (24)	▪ Reduced HbA1c and blood pressure ▪ Enhanced myocardial insulin sensitivity, systolic function and left ventricular diastolic function	[92]
		III (5238)	▪ Reduced CVD events ▪ Reduced risk of recurrent stroke	[93]
		III (5238)	▪ Reduced incidence of major adverse cardiovascular events in long term	[94]
		III (5238)	▪ Reduced all-cause mortality, non-fatal myocardial infarction and stroke	[95]
		III (3876)	▪ Reduced risk of stroke and myocardial infarction among non-diabetic patients with high CVD risk	[96]
		NA (72)	▪ Reduced neointimal volume and inflammatory markers ▪ Increased circulating miRNA-24 and flow-mediated dilation	[97]
		NA (96)	▪ Reduced neointimal hyperplasia in patients with myocardial infarction treated with primary stent implantation	[98]
		NA (97)	▪ Suppressed in-stent neointimal proliferation ▪ Reduced incidence of target lesion revascularization after percutaneous coronary intervention	[99]
		NA (28)	▪ Reduced in-stent stenosis ▪ Reduced leptin and endothelial function	[100]
		III (462)	▪ Pioglitazone was superior to sulphonylurea in slowing the progression of carotid artery intima-media thickness	[101]
		III (543)	▪ Reduced atheroma volume ▪ Improved lipid profile	[102]
		NA (56)	▪ Reduced atherosclerotic plaque inflammation more effectively than sulphonylurea	[103]
		NA (120)	▪ Lowered the recurrence of stroke, but did not reach statistical significance	[104]
		NA (15)	▪ Did not enhance antiplatelet effect	[105]
		III (300)	▪ Efficacy of pioglitazone in cardiovascular function was comparable to sulphonylurea	[106]
	Pioglitazone + metformin	IV (3028)	▪ Combined therapy of pioglitazone with metformin was comparable to combined therapy of sulphonylurea with metformin in preventing CVD events	[107]
	Rosiglitazone	III (193)	▪ No effect on CVD events ▪ Improved glycemic control and cardiometabolic risk profile	[109]
		III (1425)	▪ Reduced carotid intima-media thickness	[110]