Comparative efficacy vs. other combinations with metformin (quality of evidence)	Comparative harms vs. other combinations with metformin/class adverse effects and FDA warnings	Agents	Fair price for a 60-day supply*	Adverse effects
Sulfonylureas
Sulfonylurea plus metformin favored for weight vs. TZD plus metformin (moderate)	Higher risk for hypoglycemia than with metformin combinations with TZD, DPP-4 inhibitor, or SGLT-2 inhibitor	Glipizide (Glucotrol), 5 mg	$9	Diarrhea, gas, jitteriness, dizziness, uncontrollable shaking, red or itchy skin, rash, hives, and blisters
		Glimepiride (Amaryl), 4 mg	$14	Dizziness and nausea
		Glyburide, 5 mg	$13	Nausea and upper abdominal fullness
		Glyburide (micronized, 6 mg)	$10	Nausea and upper abdominal fullness
TZDs
TZD plus metformin favored for short-term CVD mortality (rosiglitazone [Avandia] only) (low) and A1C vs. DPP-4 inhibitor plus metformin (moderate)	TZDs increase risk for congestive heart failure	Pioglitazone (Actos), 30 mg	$30	Headache; muscle, arm, or leg pain; sore throat; and gas
	May also be associated with increased risk for fracture or bladder cancer	Rosiglitazone, 2 mg	$174	Headache, runny nose and other cold symptoms, sore throat, and back pain
DPP-4 inhibitors
DPP-4 inhibitor plus metformin favored for long-term all-cause mortality, long-term CVD mortality, and CVD morbidity vs. sulfonylurea plus metformin (low)	FDA warns that sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nesina) may be associated with potentially severe and disabling joint pain	Alogliptin, 25 mg	$346	Headache, stuffy or runny nose, sore throat, and joint pain
DPP-4 inhibitor plus metformin favored for short-term CVD morbidity vs. pioglitazone plus metformin (low)		Linagliptin, 5 mg	$728	Headache and joint pain
DPP-4 inhibitor plus metformin favored for weight vs. sulfonylurea plus metformin (high) or TZD plus metformin (moderate)		Saxagliptin, 5 mg	$746	Sore throat, headache, and joint pain
		Sitagliptin, 100 mg	$830	Stuffy or runny nose, sore throat, headache, diarrhea, nausea, and joint pain
SGLT-2 inhibitors
SGLT-2 inhibitor plus metformin favored for CVD mortality (low), A1C (moderate), weight (high), systolic blood pressure (high), and heart rate (moderate) vs. sulfonylurea plus metformin	Higher risk for genital mycotic infection than metformin alone or metformin combined with sulfonylurea or DPP-4 inhibitor	Canagliflozin, 300 mg	$888	Excessive urination, including at night; increased thirst; constipation; and dry mouth
SGLT-2 inhibitor plus metformin favored for weight and systolic blood pressure (moderate) vs. DPP-4 inhibitor plus metformin	FDA warns that canagliflozin (Invokana) may be associated with increased risk of bone fracture and decreased bone mineral density	Dapagliflozin (Farxiga), 10 mg	$896	Excessive urination, including at night, and increased thirst
		Empagliflozin (Jardiance), 25 mg	$832	Excessive urination, including at night, and increased thirst