Table 2.

Cardiovascular outcomes for diabetes medications in those with diabetes and differences by age

Medication class	Specific medication	Trial	Overall CV events	Differences in CV events by age
DPP-IV inhibitors	Alogliptin [20–22, 23••]	EXAMINE	Neutrala	No differencee
	Saxagliptin	SAVOR	Neutrala	No differencef
	Sitagliptin	TECOS	Neutrala	No differencee,f
GLP-1 agonists	Lixisenatide [24–29]	ELIXA	Neutrala	No differencee
	Liraglutide	LEADER	Benefita	Possible neutral effect in adults >=60 yearsp
	Semaglutide	SUSTAIN	Benefita	No differencee
	Exenatide ER	EXSCEL	TBDg
	Albiglutide	HARMONY outcomes	TBDg
	Dulaglutide	REWIND	TBDg
SGLT-2 inhibitors	Empagliflozin [30••, 31, 32]	EMPA-REG	Benefita	Benefit if ≥65 years, neutral if <65 years (p = 0.01 for interaction)
	Canagliflozin [33]	CANVAS	Benefita	Possibly greater benefit in adults >=65 years oldp
	Dapagliflozin	DECLARE	TBDg
Insulin	Insulin glargine [34]	ORIGIN	Neutrala	No differencee
Sulfonylureas (SUs)/meglitinides	All SUs [35, 36]		? Harmb	Not studied
	2nd generation		Neutralb	Not studied
Thiazolidinediones	Rosiglitazone [37–40]		? Harmb	Not studied
	Pioglitazone		Neutralc	Not studied
Biguanides	Metformin [12, 41]		Benefit	Not studied
Alpha-glucosidase inhibitors	Acarbose [42]	ACE	TBDg,h	TBD
Amylin agonists	Pramlintide [43]		Neutrala	Not studied

Medications in italics were subject to the 2008 FDA’s industry guidance for assessing cardiovascular risks

^aOutcome is major adverse cardiovascular event (MACE): cardiovascular death, nonfatal myocardial infarction, or nonfatal CVA

^bBased off meta-analyses of cardiovascular outcomes; no large trials

^cBased on cardiovascular outcomes, but not MACE

^dWhen stratified by <60 and ≥60 years

^eWhen stratified by <65 and ≥65 years

^fWhen stratified by <75 and ≥75 years

^gTrial ongoing

^hTrial studying both those with prediabetes and DM2

^p value for interaction by age was not significant