Pharmacotherapy for Type 2 Diabetes

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*IMPORTANT* This table has been individualized and some medications may have been removed based on patient characteristics.

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When sorting table by column, rows with equivalent values are sorted alphabetically. Therefore, the row order of equivalent values does not imply a preference. Up and down arrows (↑↓) indicate approximate relative effectiveness. Two or three arrows do not necessarily imply double or triple the effect.

Class▲	Effect on CV outcomes (people with diabetes and CVD)	Likelihood of hypoglycemia	Effect on weight	Relative A1C lowering when added to metformin	Cost	Other therapeutic considerations
Alpha-glucosidase inhibitor (acarbose)		Rare	Neutral	↓	$$	GI side effects; requires TID dosing
DPP-4 Inhibitors	Neutral: alogliptin, saxagliptin, sitagliptin	Rare	Neutral	↓ ↓	$$$	Caution with saxagliptin and heart failure; Rare joint pain
GLP1 receptor agonists	Liraglutide: Superior Exenatide LAR and lixisenatide: Neutral	Rare	↓ ↓	↓ ↓ to ↓ ↓ ↓	$$$$	GI side-effects Gallstone disease Contraindicated: Personal or family history of MTC or MEN2 Requires SC injection
Insulin	Neutral: glargine Non-inferior to glargine: degludec	High	↑ ↑	↓ ↓ ↓ ↓	$-$$$$	No dose ceiling, flexible regimens Requires SC injection
Insulin secretagogue: Meglitinide		Some	↑	↓ ↓	$$	Reduced post-prandial glycemia; requires TID-QID dosing
Metformin		Rare	↓	N/A	$	Some GI side effects
Insulin secretagogue: Sulfonylurea		Some	↑	↓ ↓	$	Gliclazide and glimepiride associated with less hypoglycemia than glyburide Poor durability
SGLT2 inhibitors	Canagliflozin and empagliflozin: superior	Rare	↓ ↓	↓ ↓ to ↓ ↓ ↓	$$$	Genital infections, UTI, hypotension Caution with renal dysfunction and loop diuretics, elderly Contraindications: Dapagliflozin and bladder cancer, canagliflozin and prior lower extremity amputation Rare DKA (may occur without hyperglycemia)
Thiazoladinediones	Neutral	Rare	↑ ↑	↓ ↓	$$	CHF, edema, fractures, cardiovascular controversy (rosiglitazone) Contraindications: pioglitazone and bladder cancer

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Acarbose	Meglitinide
DPP4-i	Metformin
GLP1RA	SU
Insulin - basal	SGLT2i
Insulin - mealtime	TZD

Recommendation:

Start healthy behaviour interventions; start metformin if glycemic targets not met within 3 months.

Start healthy behaviour interventions; start metformin immediately; consider starting a second agent concurrently.

Start healthy behaviour interventions; start insulin immediately (with or without metformin).

Encourage ongoing healthy behaviours and maintenance of glycemic control.

Start antihyperglycemic agent with demonstrated CV benefit (empagliflozin, liraglutide, canagliflozin).

start antihyperglycemic agent with demonstrated CV benefit (empagliflozin, liraglutide).

Start antihyperglycemic agent with demonstrated CV benefit (liraglutide).

Start healthy behaviour interventions.

Start healthy behaviour interventions; consider starting two agents concurrently.

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	A1C <1.5% above their target
	A1C ≥1.5% above their target
	Patient has metabolic decompensation