Trial ID	Intervention(s) and comparator(s)	Participants included in analysis (N)	Deaths (N)	Deaths (% of participants)	Participants with at least one adverse event (N)	Participants with at least one adverse event (%)	Participants with at least one severe/serious adverse event (N)	Participants with at least one severe/serious adverse event (%)
Bilezikian 2013	I: metformin	111	0	0	72	64.9	5	4.5
	C1: rosiglitazone	114	1	0.9	82	71.9	7	6.1
Campbell 1994	I: metformin	24	0	0	—	—	—	—
	C1: glipizide	24	0	0	—	—	—	—
Derosa 2003	I: metformin	56	—	—	—	—	0	0
	C1: repaglinide	56	—	—	—	—	0	0
Derosa 2004	I: metformin	75	0	0	2	2.7	0	0
	C1: glimepiride	73	0	0	0	0	0	0
Derosa 2009	I: metformin	67	—	—	—	—	—	—
	C1: rosiglitazone	69	—	—	—	—	—	—
Erem 2014	I: metformin	19	0	0	0	0	0	0
	C1: gliclazide	19	0	0	0	0	0	0
	C2: pioglitazone	19	0	0	0	0	0	0
Kahn 2006	I: metformin	1454	31	2.1	1010	69.5	331	22.8
	C1: rosiglitazone	1456	34	2.3	992	68.1	346	23.8
	C2: glibenclamide	1441	31	2.2	1013	70.3	308	21.4
Kiyici 2009	I: metformin	16	0	0	—	—	0	0
	C1: rosiglitazone	19	0	0	—	—	0	0
	C2: no intervention	15	0	0	—	—	0	0
Onuchin 2010	I: metformin	46	—	—	—	—	—	—
	C1: insulin	45	—	—	—	—	—	—
Pfützner 2011	I: metformin	328	5	1.5	224	68.3	15	4.6
	C1: saxagliptin	335	2	0.6	222	66.3	16	4.8
Rahman 2011	I: metformin	102	—	—	—	—	—	—
	C1: glimepiride	102	—	—	—	—	—	—
Schernthaner 2004	I: metformin	597	2	0.3	346	58.0	‐a	‐a
	C1: pioglitazone	597	3	0.5	316	52.9	‐a	‐a
Schweizer 2007	I: metformin	252b	2b	1.2	190b	75.4	13b	5.2
	C1: vildagliptin	519b	2b	0.6	364b	70.1	35b	6.7
Teupe 1991	I: metformin	50	—	—	—	—	—	—
	C1: no intervention	50	—	—	—	—	—	—
UKPDS 34 1998	I: metformin	342	—	—	—	—	—	—
	C1: glibenclamide	277	—	—	—	—	—	—
	C2: insulin	409	—	—	—	—	—	—
Umpierrez 2014	I: metformin	268	0	0	170	63.4	16	6.0
	C1: dulaglutide (1.5 mg/week)	269	0	0	177	65.8	15	5.6
	C2: dulaglutide (0.75 mg/week)	270	0	0	178	65.9	20	7.4
Williams‐Herman 2010	I: metformin (1000 mg/day)	182	1c	0.5	74d	40.7	7d	5.5
	I2: metformin (2000 mg/day)	182	0c	0	99d	54.4	9d	7.7
	C1: sitagliptin	179	0c	0	71d	39.7	13d	8.4
Yamanouchi 2005	I: metformin	39	—	—	0	0	0	0
	C1: pioglitazone	38	—	—	4	10.5	0	0
	C2: glimepiride	37	—	—	1	2.7	0	0
—: denotes not reported a7.4% and 4.9% of adverse events in the metformin and pioglitazone group, respectively, were judged to be serious adverse events bFrom the initial 52 weeks of intervention cFrom full article. Triasl register reports 0 deaths in all intervention groups dFrom full article. Trials register reports 10, 14 and 15 serious adverse events for metformin 1000 mg/day, 2000 mg/day and sitagliptin 100 mg/day, respectively C: comparator; I: intervention; N: number of participants; UKPDS: United Kingdom Prospective Diabetes Study.