PPAR𝛾 Agonists: Potential as Therapeutics for Neovascular Retinopathies

Table 3

Comparison of pharmacological and other relevant properties of thiazolidinedione (TZD) full PPAR𝛾 agonists and dual angiotensin II type 1 receptor blocker/selective PPAR𝛾 modulator (ARB/SPPAR𝛾M).

Parameter	TZDs^†			ARBs^*
	Troglitazone	Pioglitazone	Rosiglitazone	Telmisartan	Irbesartan
Primary pharmacological target	PPAR𝛾	PPAR𝛾	PPAR𝛾	AT1-R	AT1-R
Type of PPAR𝛾 agonists	Full PPAR𝛾 agonists			Selective PPAR𝛾 modulator (SPPAR𝛾M)
Drug class (common names)	Thiazolidinedione (TZDs)			Angiotensin receptor blockers (ARBs)
PPAR𝛾 activation (EC50in𝜇M)	0.55	0.58	0.043	4.5	27
Therapeutic indication	Treatment of type 2 diabetes mellitus			Treatment of hypertension
Primary therapeutic mechanism	Increase insulin sensitivity			Lower blood pressure
Serious adverse effect (Black box warning)	Fluid retention/weight gain/heart failure			None	None
Supplier/Pharmaceutical Co.	Sigma-Aldrich, St. Louis, Mo, USA	Takeda Pharmaceuticals North America, Deerfield, Ill, USA	GlaxoSmithKline, NC, USA	Boehringer- Ingelheim Pharmaceuticals, Inc., Ridgefield, Conn, USA	Sanofi-Aventis, Bridgewater, NJ, USA

^†Thiazolidinedione full PPAR𝛾 agonists; troglitazone was withdrawn from the market (1998) because of association with rare cases of fatal hepatic failure. Rosiglitazone and pioglitazone have no such known association.^*Other FDA-approved ARBs had EC₅₀ values >100 𝜇M (see [37, 38]). EC₅₀ values shown were determined using the standard PPAR𝛾-GAL4 transactivation assays.