Table 2.

Study-level features of the integrated analyses describing the CV safety of DPP-4 inhibitors and GLP-1 receptor agonists trialled in randomized controlled studies

References	Incretin (dosage regimen)	No. of studies	Minimum trial duration (weeks)	Mean trial duration (weeks)	Analysis design
Abbas, 2016 [42]	Alogliptin 6.25–25 mg/daya; sitagliptin 100 mg/dayb; saxagliptin 2.5–5 mg/dayc	3	–	130d	Post hoc
Engel, 2013 [23]e	Sitagliptin (100 mg/day)	25	12	34	Post hoc
Iqbal, 2014 [24]f	Saxagliptin (2.5, 5, and 10 mg/day)g	20	4	59	Post hoc (8 studies) Prespecified (12 studies)
Kundu, 2016 [39]	Alogliptin 6.25–25 mg/daya; sitagliptin 100 mg/dayb; saxagliptin 2.5–5 mg/dayc	3	–	–	Post hoc
Lehrke, 2014 [22]	Linagliptin 5 mg/dayh	22	<2i	22	Post hoc
McInnes, 2015 [25]	Vildagliptin (50 mg od and bd)	37	12	50.3 versus 48.7j	Post hoc
Rosenstock, 2015 [21]	Linagliptin (≥5 mg/day)	19	12	35	Prespecified
White, 2013 [26]k	Alogliptin (≥12.5 mg/day)	11	12	29	Prespecified
Udell, 2015 [37]	Alogliptin 6.25–25 mg/daya; saxagliptin 2.5–5 mg/dayc	2	–	93	Post hoc
Agarwal, 2014 [33]	DPP-4 inhibitors	82	24	44	Post hoc
Kongwatcharapong, 2016 [38]	DPP-4 inhibitors	54	12	59	Post hoc
Li, 2016 [40]	DPP-4 inhibitors	43	12	61	Post hoc
Monami, 2013 [29]	DPP-4 inhibitors	63	24	46	Post hoc
Monami, 2014 [34]	DPP-4 inhibitors	82	24	47	Post hoc
Patil, 2012 [30]	DPP-4 inhibitors	18	24	52	Post hoc
Savarese, 2015 [36]	DPP-4 inhibitors	94	12	29d	Post hoc
Wang, 2016 [41]	DPP-4 inhibitors	68	24	24–52l	Post hoc
Wu, 2013 [31]	DPP-4 inhibitors	8	18	43	Post hoc
Wu, 2014 [35]	DPP-4 inhibitors	50	24	45	Post hoc
Zhang, 2014 [32]	DPP-4 inhibitors	12	18	NR	Post hoc
Fisher, 2015 [53]	Albiglutide (15–50 mg/week or 30 mg biweekly)	9	16	104	Prespecified
Ferdinand, 2016 [54]	Dulaglutide (0.1–1.5 mg/week)	9	12	45	Prespecified
Ratner, 2011 [51]	Exenatide (2.5, 5, and 10 µg bd)	12	12	23	Post hoc
Marso, 2011 [50]m	Liraglutide (0.045–3.0 mg/day)	15	26	NR	Post hoc
Seshasai, 2015 [52]	Taspoglutide 20 mg/week	9	24	52	Prespecified
Li, 2016 [56]	GLP-1 receptor agonists	21	16	78	Post hoc
Monami, 2013 [12]	GLP-1 receptor agonists	25	24	42	Post hoc
Sun, 2012 [55]	GLP-1 receptor agonists	45	8	27	Post hoc
Wang, 2016 [41]m	Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide	35	24	24–156 l	Post hoc

bd twice daily, od once daily, NR not reported

^a25 mg in patients with an estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m² of body surface area; 12.5 mg in patients with an eGFR of 30 to <60 mL/min/1.73 m²; and 6.25 mg in patients with an eGFR of <30 mL/min/1.73 m² [28]

^bOr 50 mg daily if the baseline eGFR was ≥30 and <50 mL/min/1.73 m² [44]

^c2.5 mg daily in patients with an eGFR ≤ 50 mL/min/1.73 m² [43]

^dMedian

^eDid not include data from TECOS [44]

^fDid not include data from SAVOR-TIMI 53 [43]

^g20, 40, or 100 mg/day was administered in one phase 2b study

^hOne of the 22 studies tested linagliptin 2.5 mg/day

ⁱNearly two-thirds of patients received treatment for at least 24 weeks [22]

^jMean duration of exposure for vildagliptin versus comparators [25]

^kDid not include data from EXAMINE [28]

^lRange of medians for studies of each DPP-4 inhibitor or GLP-1 receptor agonist

^mDid not include data from LEADER [57]