Table 1.

Main targets and safety of SPIOMET

	Main targets	Side effects to be avoided	Efficacy with low doses	Safety concerns with low doses
SPI (50 mg/d)	Less androgen effect More BAT activity (CXCL14)	Hyperkalaemia	+	None
PIO (7.5 mg/d)	Less hepatic fat More HMW-adip	Weight gain	+	None
MET (850 mg/d)	Multiple mechanisms Less appetite (GDF15)	Abdominal discomfort	+	None
SPIOMET	Improved metabolic health, including less ectopic fat and more ovulations	Safety concerns	+  +  +	None

Abbreviations: BAT Brown adipose tissue, CXCL14 C-X-C motif chemokine ligand-14, GDF15 Growth-and-differentiation factor 15, HMW-adip High molecular weight adiponectin, MET Metformin, PIO Pioglitazone, SPI Spironolactone, SPIOMET Spironolactone, pioglitazone and metformin