Trial ID	Intervention(s) and comparator(s)	Participants included in analysis (N)	Deaths (N)	Deaths(%)	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 (%)
Alfawaz 2018	I: metformin	59	—	—	—	—	—	—
	C1: intensive diet plus exercise	73	—	—	—	—	—	—
	C2: standard care	85	—	—	—	—	—	—
PREVENT‐DM 2017	I1: metformin	29	0	0	10	34.4	0	0
	C1: intensive diet plus exercise	33	0	0	0	0		0
	C2: standard care	30	0	0	0	0	0	0
Zeng 2013	I: metformin	68	—	—	—	—	—	—
	C1: Standard care	66	—	—	—	—	—	—
	C2: pioglitazone	70	—	—	—	—	—	—
Zhao 2013	I: metformin plus intensive diet plus exercise	45	—	—	Gastrointestinal symptoms: 1	Gastrointestinal symptoms: 2.2	—	—
	C: intensive diet plus exercise	46	—	—	Gastrointestinal symptoms: 0	Gastrointestinal symptoms: 0	—	—
Iqbal Hydrie 2012	I1: metformin plus intensive diet and physical activity	95	0	0	—	—	—	—
	C1: intensive diet and physical activity	114	0	0	—	—	—	—
	C2: standard care	108	2	1.9	—	—	—	—
Liao 2012	I: metformin	51	—	—	—	—	Cerebral haemorrhage: 1	Cerebral haemorrhage: 2.0
	C: acarbose	50	—	—	—	—	Lung cancer: 1 hepatitis: 1	Lung cancer: 2.0 hepatitis: 2.0
Ji 2011	I1: metformin	52	—	—	—	—	—	—
	C1: Intensive diet plus exercise	60	—	—	—	—	—	—
	C2: standard care	64	—	—	—	—	—	—
Lu 2010	I: metformin	115	—	—	Diarrhoea: 11 nausea: 14 vomiting: 7 abdominal distension: 11 weak: 17 indigestion: 15 abdominal discomfort and headache: 8 abnormal defecate: 16 low blood sugar: 4 muscle pain: 2 dizzy: 7 rash: 1 sweating increases: 2 taste abnormalities: 13 chest discomfort: 2 flu symptoms: 1 weight loss, etc: 33	Diarrhoea: 9.5 nausea: 12 vomiting: 6.1 abdominal distension: 9.5 weak: 14.8 indigestion: 13 abdominal discomfort and headache: 7.0 abnormal defecate: 13.9 low blood sugar: 3.5 muscle pain: 6.1 dizzy: 0.8 rash sweating increases: 1.7 taste abnormalities: 11.3 chest discomfort: 1.7 flu symptoms: 0.8 weight loss, etc: 28.7	—	—
	C: standard care	111	—	—	Diarrhoea: 7 nausea: 5 vomiting: 5 abdominal distension: 6 weak: 15 indigestion: 15 abdominal discomfort and headache: 3 abnormal defecate: 4 low blood sugar: 2 muscle pain: 0 dizzy: 8 rash: 0 sweating increases: 2 taste abnormalities: 1 chest discomfort: 1 flu symptoms: 2 weight loss, etc: 10	Diarrhoea: 6.3 nausea: 4.5 vomiting: 4.5 abdominal distension: 5.4 weak: 13.5 indigestion: 13.5 abdominal discomfort and headache: 2.7 abnormal defecate: 3.6 low blood sugar: 1.8 muscle pain: 0 dizzy: 7.2 rash: 0 sweating increases: 1.8 taste abnormalities: 0.9 chest discomfort: 0.9 flu symptoms: 1.8 weight loss, etc: 9	—	—
BIGPRO1 2009	I: metformin	21	—	—	—	—	—	—
	C: placebo	36	—	—	—	—	—	—
Chen 2009	I: metformin	44	—	—	—	—	—	—
	C: standard care	46	—	—	—	—	—	—
Jin 2009	I: metformin	45	—	—	Hypoglycaemia 0	Hypoglycaemia 0	Severe gastrointestinal reactions: 3	Severe gastrointestinal reactions: 6.7
	C1: standard care	41	—	—	Hypoglycaemia 0	Hypoglycaemia 0	—	—
	C2: rosiglitazone	41	—	—	Facial oedema: 1 intolerance of both lower limbs: 2 hypoglycaemia: 0	Facial oedema: 2.4 intolerance of both lower limbs: 4.9 hypoglycaemia: 0	0	0
Li 2009	I: metformin	77	—	—	—	—	—	—
	C: intensive diet plus exercise	83	—	—	—	—	—	—
Wang 2009	I: metformin	30	—	—	Gastrointestinal symptoms: 2	Gastrointestinal symptoms: 6.7	—	—
	C: standard care	32	—	—	—	—	—	—
IDPP‐1 2006	I1: metformin	128	0	0	—	0	—	—
	I2: metformin plus intensive diet and physical activity	121	1	0.8	—	—	—	—
	C1: intensive exercise plus diet	120	1	0.8	—	—	—	—
	C2: standard care	133	1	0.8	—	—	—	—
Maji 2005	I1: metformin	—	—	—	—	—	—	—
	C1: intensive lifestyle intervention	—	—	—	—	—	—	—
	C2: rosiglitazone	—	—	—	—	—	—	—
	C3: acarbose	—	—	—	—	—	—	—
Fang 2004	I: metformin	44	1	2.3	Diarrhea: 3	Diarrhea: 6.8	Death (liver cancer): 1	Death (liver cancer): 2.3
	C1: acarbose	45	0	0	Abdominal distension and diarrhoea: 3 rash: 1 frequent venting: 1	Abdominal distension and diarrhoea: 6.7 rash: 2.2 frequent venting: 2.2	—	—
	C2: intensive exercise and diet	36	0	0	0	0	0	0
	C3: standard care	35	0	0	0	0	0	0
DPP/DPPOS 2002	I: metformin	1073	6	0.6	Musculoskeletal symptoms: 20.0 events/100 person yearsa gastrointestinal symptoms: 77.8 events/100 person years	Musculoskeletal symptoms: — gastrointestinal symptoms: —
	C1: intensive exercise and diet	1079	3	0.3	Musculoskeletal symptoms: 24.1 events/100 person years gastrointestinal symptoms: 12.9 events/100 person years	Musculoskeletal symptoms: — gastrointestinal symptoms: —	—	—
	C2: placebo	1082	5	0.5	Musculoskeletal symptoms: 21.1 events/100 person years gastrointestinal symptoms: 30.7 events/100 person years	Musculoskeletal symptoms: — gastrointestinal symptoms: —	—	—
Lu 2002	I1: metformin	80	—	—	—	—	—	—
	C1: standard care	75	1	1.3	—	—	Death (cerebral thrombosis with pulmonary infection): 1	Death (cerebral thrombosis with pulmonary infection): 1.3
	C2: standard care plus diet instruction every 6th month	64	—	—	—	—	—	—
	C3: standard care plus fibre diet	51	—	—	—	—	Stomach cancer: 1	Stomach cancer: 2.0
Li 1999	I: metformin	33	0	0	(1) Mild diarrhoea and nausea: 3	(1) 9.1	—	—
	C: placebo	37	0	0	(1) Mild nausea: 6 (2) raised liver enzymes: 1	(1) 16 (2) 2.7	—	—
Papoz 1978	I1: metformin (plus placebo)	—	—	—	—	—	—	—
	C1: glibenclamide plus placebo	—	—	—	—	—	—	—
	C2: placebo	—	—	—	—	—	—	—
—: denotes not reported aAll adverse events from DPP are calculated from number of events/100 person years; some participants might have experienced more than one event. Therefore only the number of participants with an event cannot be calculated C: comparator; I: intervention.