Table 1: Description of included randomized controlled trials

First author, year of publication	Inclusion criteria		Trial duration (w)	Baseline patient characteristics								Patients with heart failure (n/N)
First author, year of publication	Other anti- hyperglycemic agent(s)	A1C range (%)	Trial duration (w)	Prim. outcome	Mean age (yr)	Male (%)	Caucasian (%)	BMI (kg/m²)	DM (yr)	Mean A1C (%)	On insulin (%)	DPP4 inhibitor	Placebo
Trials with primary cardiovascular outcomes
Scirica, 2013, 2014 (SAVOR-TIMI 53)^4,5 (saxagliptin)	-	6.5-12	110 (med)	MACE	65	67	75	31	10.3 (med)	8.0	41	289/8280	228/8212
White, 2013 (EXAMINE)^6,7 (alogliptin)	-	6.5-11 (7-11)	76 (med)	MACE	61 (med)	68	73	29 (med)	7.2 (med)	8.0	30	106/2701	89/2679
Green, 2015 (TECOS)^8,25 (sitagliptin)	-	6.5-8	156 (med)	MACE	66	71	68	30	9.4 (med)	7.2	23	228/7332	229/7339
Trials with primary metabolic outcomes
Alogliptin
Nauck, 2009²⁶	Met	7-10	26	A1C	55	50	77	32	6	7.9	0	1/423	0/104
DeFronzo, 2008²⁷	-	7-10	26	A1C	53	53	67	n/r	n/r	7.9	0	0/264	0/64
Pratley, 2009²⁸	Sulf	7-10	26	A1C	57	52	71	30	7.7	8.1	0	1/401	0/99
Pratley, 2009²⁹	Pio	7-10	26	A1C	55	58	74	33	7.6	8.0	0	2/397	0/97
Rosenstock, 2009³⁰	Ins	≥ 8	26	A1C	55	41	65	32	12.6	9.3	100	0/261	0/129
Rosenstock, 2010³¹	Pio 30	7.5-11	26	A1C	53	49	80	31	3.2	8.8	0	0/327	0/163
Pratley, 2014³²	± Met	7.5-10	26	A1C	54	54	68	31	4.0	8-8.5	0	0/442	0/326
DeFronzo, 2012³³	Met ± Pio	7.5-10	26	A1C	54	45	71	3	6.2	8.5	0	0/1037	2/516
Mita, 2016³⁴	+Var	7-9.3	104	Intimal thickness	65	58	0	25	8.6	7.3	0	0/161	0/161
Linagliptin
Gomis, 2011³⁵	±Met	7.5-10 (11)	24	A1C	55	54	67	29	n/r	8.6	0	0/259	0/130
Haak, 2012,³⁶ 2013³⁷	±Met	7.5-10 (11)	24	A1C	55	54	67	29	2.5	8.7	0	2/428	0/363
Owens, 2011³⁸	+Met and Sulf	7-10	24	A1C	58	47	47	28	> 5	8.1	0	0/792	0/263
Taskinen, 2011³⁹	+Met	7-10	24	A1C	57	54	76	30	5	8.1	0	0/523	0/177
Thrasher 2014^40,41	-	7.5-11	24	A1C	54	54	0 (Black)	33	5-6	8.7	0	0/106	0/120
Barnett, 2013⁴²	-	≥ 7 (age ≥ 70)	24	A1C	75	68	97	30	10-12	7.8	21	0/162	0/79
Bajaj, 2014⁴³	+Met and Pio	7.5-10	24	A1C	54	49	27	28	1-2	8.4	0	0/183	0/89
Del Prato, 2011⁴⁴	-	7-10	24	A1C	56	48	54	29	n/r	8	0	0/336	0/167
McGill, 2013⁴⁵	-	7-10 (CRI)	52	A1C	64	60	74	32	> 5	8.2	82	2/68	1/65
Yki-Jarvinen, 2013⁴⁶	-	7-10	52	A1C	60	52	80	31	> 5	8.3	100	3/631	2/630
ClinicalTrials.gov⁴⁷	+Pio	7-10.5	84	A1C	57	53	n/r	n/r	n/r	8.1	0	0/392	1/409
Chen, 2015⁴⁸	-	7-10	24	A1C	54	59	0 (Asian)	25	n/r	8.0	0	0/200	0/99
ClinicalTrials.gov⁴⁹	+Met	7-10	24	A1C	56	50	0 (Asian)	26	n/r	8.0	0	0/205	0/100
DeFronzo, 2015⁵⁰/ Lewin, 2015⁵¹	±Met	7-10.5	24	A1C	55	54	74	31	~5	8.0	0	0/545	0/551
ClinicalTrials.gov⁵²	+Met	7.5-11	24	A1C	51	62	n/r	n/r	n/r	n/r	n/r	0/294	0/289
Wu, 2015⁵³	-	7-10	24	A1C	52	59	0 (Chinese)	24	0	8.0	0	0/33	0/22
ClinicalTrials.gov⁵⁴	+Empa and Met	7-10.5	24	A1C	57	57	n/r	n/r	n/r	n/r	n/r	0/238	0/240
Saxagliptin
Pfützner, 2011⁵⁵/Jadzinsky, 2009⁵⁶	+Met	8-12	76	A1C	52	49	76	30	1.7	9.4	0	1/643	2/328
Barnett, 2013⁵⁷	+Ins ±Met	7.5-11	52	A1C	57	41	78	32	12	8.7	100	2/304	0/151
Chacra, 2011⁵⁸	+Sulf	7.5-10	76	A1C	55	45	59	29	7	8.4	0	1/501	0/267
DeFronzo, 2009⁵⁹/Rosentock, 2013⁶⁰	+Met	7-10	24 (208 for mort)	A1C	55	51	82	31	6.5	8.0	0	3/564	2/179
Frederich, 2012⁶¹	-	7-10	24	A1C	55	46	70	31	1.7	8.0	0	0/291	0/74
Hollander, 2011⁶²	+TZD	7-10.5	76	A1C	54	50	55	30	5.2	8.3	0	0/381	1/184
Nowicki, 2011⁶³	+var	7-11 (CRI)	52	A1C	67	43	100	31	16.6	8.3	75	1/85	2/85
Pan, 2012⁶⁴	-	7-10	24	A1C	51	55	0 (Asian)	26	1	8.1	0	0/284	0/284
Rosenstock, 2009⁶⁵/Rosenstock, 2013⁶⁰	-	7-10	24 (208 for mort)	A1C	53	51	85	32	2.6	7.9	0	1/306	0/95
Moses, 2014⁶⁶	+Met and Sulf	7-10	24	A1C	57	60	45	29	n/r	8.3	0	0/129	0/128
Rosenstock, 2015⁶⁷	+Met and dap	8-12	24	A1C	54	49	70	32	7.3	8.9	0	0/179	0/179
Matthaei, 2015⁶⁸	+Met and dap	8-11.5	24	A1C	55	47	88	31	7.7	7.9	0	1/ 53	2/ 62
Sitagliptin
Charbonnel, 2006⁶⁹	+Met	7-10	24	A1C	55	57	64	31	4.6	8.0	0	1/464	0/237
Hermansen, 2007⁷⁰	+Sulf ±Met	7.5-10.5	24	A1C	56	53	63	31	8.8	8.3	0	1/222	0/219
Henry, 2014⁷¹	+Pio	7.5-11	54	A1C	52	56	67	31	3.9	8.9	0	2/691	0/693
Raz, 2008⁷²	+Met	8-11	30	A1C	55	46	44	30	7.9	9.2	0	0/96	0/94
Vilsbøll, 2011⁷³	+Ins ±Met	7.5-11	24	A1C	58	51	70	31	12	8.7	100	0/322	2/319
Williams-Herman, 2010⁷⁴/ Goldstein, 2007⁷⁵	±Met	7.5-11	104	A1C	53	49	52	32	4.5	8.8	0	1/372	0/364
Yoon, 2012,⁷⁶ 2011⁷⁷	+Pio	8-12	54	A1C	51	54	52	30	2.3	9.5	0	0/261	0/259
ClinicalTrials.gov⁷⁸	-	7-10	24	A1C	49	56	0 (India)	n/r	n/r	n/r	0	0/107	0/106
Yang, 2011⁷⁹	+Met	7-10	24	A1C	54	48	0 (Asian)	26	5.1	7.8	0	0/283	0/287
ClinicalTrials.gov⁸⁰	+Met	6.5-11	24	A1C	55	26	n/r	29	8.4	8.5	0	0/36	0/9
Barzilai, 2011⁸¹	-	7-10 (age ≥ 65)	24	A1C	72	47	79	31	7.1	7.8	0	0/102	0/104
Yang, 2012⁸²	+Met	7.5-11	24	A1C	55	51	0 (Chi-nese)	25	6.9	8.5	0	0/197	0/198
Rosenstock, 2006⁸³	+Pio	7-10	24	A1C	56	56	73	31	6.1	8.0	0	0/175	0/178
Aschner, 2006⁸⁴	-	7-10	24	A1C	54	52	51	30	4.4	8.0	0	0/488	0/253
Fonseca, 2013⁸⁵	+Met +Pio	7.5-11	26	A1C	56	62	50	30	9.8	8.7	0	0/157	0/156
Olansky, 2011⁸⁶	+Met	≥ 7.5	44	A1C	50	57	80	33	3.4	9.9	0	1/625	0/621
ClinicalTrials.gov⁸⁷	+Met	6/6.5-9	44	β-cell function	61	67	62	33	3.0	6.1	0	0/10	0/11
Dobs, 2013⁸⁸	+Met and Rosi	7.5-11	54	A1C	55	58	51	30	9.3	8.8	0	0/170	0/92
Moses, 2016⁸⁹	+Met and Sulf	7.5-10.5	24	A1C	55	46	n/r	n/r	n/r	8.4	0	0/210	0/212
Lavalle-González, 2013⁹⁰	-	7-10.5	26	A1C	55	48	72	32	6.8	7.9	0	1/366	0/183
Mathieu, 2015⁹¹	+Glar ±Met	7.5-11	24	A1C	59	48	70	32	13.5	8.7	100	0/329	0/329
Roden, 2013⁹²	-	7-10	76	A1C	55	59	34	28	< 5	7.9	0	1/223	0/223
ClinicalTrials.gov⁹³	+Acar	n/r	24	A1C	57	51	n/r	n/r	n/r	8.1	0	0/191	0/189
Skrivanek, 2014⁹⁴	+Met	7-9.5	26	A1C	54	49	51	31	7	8.1	0	0/355	0/177
ClinicalTrials.gov⁹⁵	+Met	n/r	156	A1C	55	47	72	n/r	n/r	n/r	n/r	1/302	0/101
Ji, 2016⁹⁶	±Met	7(0.5)-10(11)	24	A1C	53	61	0 (Chi-nese)	n/r	n/r	8.7	0	0/367	0/376
ClinicalTrials.gov⁹⁷	+Met and Ins	7-10	24	A1C	56	52	49	29	9.1	8.4	100	0/383	0/192
ClinicalTrials.gov⁹⁸	+Sulf ±Met	7.5-11	24	A1C	57	50	n/r	n/r	n/r	8.6	0	0/248	0/249
ClinicalTrials.gov⁹⁹	+Ins ±Met	7.5-11	24	A1C	58	53	0 (Chi-nese)	n/r	n/r	n/r	100	0/234	0/233
ClinicalTrials.gov¹⁰⁰	+Met	7.1-11	28	A1C	54	56	81	32	8.2	8.5	0	0/122	0/61
Ishikawa, 2014¹⁰¹	-	< 6.5	52	Carotid artery intima thickness	71	85	0 (Jap-anese)	25	n/r	5.6	0	0/37	0/39
Derosa, 2012^102-104	+Met	> 8.0	52	A1C	55	48	100	29	0.5	8.1	0	0/91	0/87
Derosa, 2014¹⁰⁵	+Var	> 7.0	104	A1C	n/r	49	100	29	n/r	8.1	0	0/102	0/103
Chien, 2011¹⁰⁶	+Var	≥ 7.0	24	A1C	73	58	0 (Chi-nese)	26	13.6	9.7	0	0/49	0/48
Weinstock, 2015¹⁰⁷	+Met	7/8-9.5	26	A1C	54	49	51	31	7.0	8.1	0	0/315	0/177
Mita, 2016¹⁰⁸	+Var	≥ 6.6	104	Intimal thickness	64	60	0 (Jap-anese)	25	17.3	8.1	100	0/137	0/137
ClinicalTrials.gov¹⁰⁹	-	n/r	24	A1C	60	69	0 (Jap-anese)	n/r	n/r	n/r	0	0/164*	0/82
Vildagliptin
Bosi, 2007¹¹⁰	+Met	7.5-11	24	A1C	54	57	74	33	6.3	8.4	0	0/360	0/181
Bosi, 2009¹¹¹	+Met	7.5-11	24	A1C	53	58	73	31	4.1	8.7	0	0/292	0/292
Fonseca, 2007¹¹²	+Ins	7.5-11	24	A1C	59	51	71	33	14.7	8.4	100	0/144	0/152
VIVIDD, 2014¹¹³	-	6.5-10 (LVEF < 40)	52	LVEF	63	77	n/r	29	n/r	7.8	34	13/128	10/125
Scherbaum, 2008^114,115	-	6.2-7.5	104	A1C	63	59	99	30	2.6	6.7	0	0/156	0/150
Strain, 2013¹¹⁶	-	7-10 (age > 70)	24	A1C	75	45	97	30	11.4	7.9	0	1/139	1/139
Vollmer, 2009¹¹⁷	+Met	6.5-8	24	A1C	61	46	96	n/r	n/r	7.2	0	0/274	0/131
Garber, 2007¹¹⁸	+Pio	7.5-11	24	A1C	54	43	69	32	4.7	8.7	0	1/305	1/158
Garber, 2008¹¹⁹	+Sulf	7.5-11	24	A1C	58	59	69	31	7.1	8.5	0	0/339	0/176
Yang, 2015¹²⁰	+Sulf	7.5-11	24	A1C	59	57	0 (Chi-nese)	25	6.9	8.7	0	0/143	0/136
Foley, 2011¹²¹/Bunck, 2012¹²²	-	≤ 7.5	52	β-cell function	57	59	93	30	1.0	6.0	0	0/29	0/30
Pan, 2012¹²³	+Met	7-10	24	A1C	54	47	0 (Chi-nese)	25	5	8.1	0	0/294	0/144
Lukashevich, 2014¹²⁴	+Met ±Sulf	7.5(8.5)-11	24	A1C	55	48	23	28	7.3	8.8	0	0/157	0/160
Macauley, 2015¹²⁵	+Met	≤ 7.6	26	Liver TG + Ins Sens	61	64	n/r	30	1.0	6.0	0	0/20	0/19
Ahren, 2004,¹²⁶ 2005¹²⁷	+Met	7-9.5	52	A1C	57	37	99	30	5.6	7.7	0	0/56	0/51
Goodman, 2009¹²⁸	+Met	7.5-11	24	A1C	55	58	66	32	n/r	8.6	0	0/248	0/122
Ito, 2011¹²⁹	-	> 7.0 (ESRD)	24	A1C	67	69	0 (Jap-anese)	23	n/r	6.7	0	0/30	0/21
Derosa, 2012^130-132	+Met	8.1-10.9	52	A1C+ β-cell func-tion	53	51	100	28	0.5	8.2	0	0/84	0/83
Zografou, 2015¹³³	+Met	7-9	26	Arter. stiffness	54	59	n/r	32	n/r	8.1	0	0/32	0/32
Gemigliptin
Yang, 2013¹³⁴	-	7-11	24	A1C	53	58	0 (Ind/Korean)	26	3	8.3	0	0/87	0/87
Teneligliptin
ClinicalTrials.gov¹³⁵	+Met	7-10	24	A1C	58	56					0	0/359	0/88
Anagliptin
Yang, 2015¹³⁶	-	6.5-10	24	A1C	56	54	0 (Korean)	25	3.6	7.1	0	0/68	1/40

Note: acar = acarbose, BMI = body mass index, CRI = chronic renal insufficiency, dap = dapagliflozin, DPP-4 = dipeptidyl peptidase-4, empa = empagliflozin, ESRD = end-stage renal disease, glar = glargine, Ind = Indian, ins = insulin, LVEF = left ventricular ejection fraction, MACE = major adverse cardiovascular events, med = median, met = metformin, n/N = number of patients with heart failure/total number of patients, n/r = not reported, pio = pioglitazone, rosi = rosiglitazaone, sulf = sulfonylurea, TZD = thiazolidinedione, var = various hypoglycemic agents.

*Randomized patients to 3 groups comparing both sitagliptin and omarigliptin to placebo; 0/166 heart failure events in the omarigliptin group.