Study ID	Endpoints	Definition
Bilezikian 2013	All‐cause mortality	"Deaths" (IO)
	Serious adverse events	NDb
	Health‐related quality of life	—
	Non serious adverse events	"Adverse events" (SO)
	Cardiovascular mortality	"Cardiac death" (IO)
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	—
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	"From weeks 8 to 16, subjects with mean daily glucose 6.1 mmol/L at the maximum tolerated doses of blinded RSG or MET received open‐label sulfonylurea. After 4 months of double‐blind study medication, subjects with HbA1c > 7.5% at the maximum dose of medication could up‐titrate or add open‐label sulfonylurea at the discretion of the investigator." (IO)
Campbell 1994	All‐cause mortality	NDb
	Serious adverse events	NDb
	Health‐related quality of life	—
	Non serious adverse events	—
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	—
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	NDb
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	—
Derosa 2003	All‐cause mortality	NDb
	Serious adverse events	"Serious adverse events" (IO)
	Health‐related quality of life	—
	Non serious adverse events	—
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	"Severe hypoglycaemia" (IO)
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	—
Derosa 2004	All‐cause mortality	NDb
	Serious adverse events	"Serious adverse events" (IO)
	Health‐related quality of life	—
	Non serious adverse events	"Adverse experiences" (SO)
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	"Severe hypoglycaemia" (IO)
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	—
Derosa 2009	All‐cause mortality	NDb
	Serious adverse events	"All adverse events" (IO)
	Health‐related quality of life	—
	Non serious adverse events	"All adverse events" (SO)
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	—
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	—
Erem 2014	All‐cause mortality	NDb
	Serious adverse events	NDb
	Health‐related quality of life	—
	Non serious adverse events	"Adverse events and side effects" (SO)
	Cardiovascular mortality	"Cardiovascular death" (IO)
	Non‐fatal myocardial infarction	"Myocardial infarction"c (IO)
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	"Hypoglycaemia"d (IO)
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	"Congestive heart failure" (IO)
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	—
Kahn 2006	All‐cause mortality	"Deaths from all causes" (IO)
	Serious adverse events	"Any event that was fatal, life threatening, or disabling; resulted in hospitalization or prolonged a hospital stay; was associated with a congenital abnormality, cancer, or a drug overdose (either accidental or intentional); or was regarded by the investigator as serious or suggested any substantial hazard, contraindication, side effect, or precaution." (IO)
	Health‐related quality of life	"Medical Outcomes Study 36‐Item Short‐Form Health Survey" (SO)
	Non serious adverse events	"Adverse events" (SO)
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	"Myocardial infarction… Nonfatal" (IO)
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	"Hypoglycaemia... Serious Events" (IO)
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	"Congestive heart failure" (AO)
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	"Treatment failure, which was defined as confirmed hyperglycemia (fasting plasma glucose level > 180 mg/dL) on consecutive (IO, AO)
Kiyici 2009	All‐cause mortality	NDb
	Serious adverse events	"Serious adverse effect" (IO)
	Health‐related quality of life	—
	Non serious adverse events	"Side effects" (SO)
	Cardiovascular mortality	NDb
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	—
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	—
Onuchin 2010	All‐cause mortality	NDb
	Serious adverse events	NDb
	Health‐related quality of life	"Medical Outcomes Study 36‐2‐item Short Form Health Survey" (SF‐36v2)" "Total physical health component" "Total mental health component" (SO)
	Non serious adverse events	—
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	NDb
	Anthropometric measures	BMI (IO)
	Glycaemic control	HbA1c (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	—
Pfützner 2011	All‐cause mortality	"Deaths" (IO)
	Serious adverse events	"Serious adverse events" (IO)
	Health‐related quality of life	—
	Non serious adverse events	"Adverse events" (SO)
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	"Hypoglycemia" (IO)
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	"Patients were eligible for rescue therapy based on progressively strict glycaemic control criteria over 24 weeks if FPG levels were as follows: > 240 mg/dL (week 6); > 220 mg/dL (week 8) and > 200 mg/dL (weeks 12, 16, 20 and 24). Patients who met rescue criteria were entered directly into the long‐term extension period, where they were administered open‐label pioglitazone 15 mg, which could be uptitrated to 45 mg, in addition to blinded study medication." (IO)
Rahman 2011	All‐cause mortality	NDb
	Serious adverse events	NDb
	Health‐related quality of life	—
	Non serious adverse events	—
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	—
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	—
Schernthaner 2004	All‐cause mortality	"Deaths" (IO)
	Serious adverse events	"AEs... judged as severe" (IO)
	Health‐related quality of life	—
	Non serious adverse events	"Adverse events" (SO)
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	—
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	—
Schweizer 2007	All‐cause mortality	"Deaths" (IO)
	Serious adverse events	"Serious adverse effects" (IO)
	Health‐related quality of life	—
	Non serious adverse events	"Adverse events" (SO)
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	"Severe hypoglycaemia was defined as any episode requiring the assistance of another party" (IO)
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	In the 52 week extension period: "Pioglitazone was added to the blinded study drug from the first visit of the extension as rescue medication for patients with confirmed fasting plasma glucose > 10 mmol/L, according to the investigator's clinical judgment and prescribing guidelines" (IO)
Teupe 1991	All‐cause mortality	NDb
	Serious adverse events	NDb
	Health‐related quality of life	—
	Non serious adverse events	"complaints according to a standardized questionnaire (side effects)" (SO)
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	—
	Non‐fatal stroke	—
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	—
	Anthropometric measures	Weight (IO)
	Glycaemic control	HbA1c (IO)
	Lactic acidosis	NDb
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	"Confirmed therapeutic failure" "HbA1c values exceeding 10 % were re‐checked after 4 weeks. If the elevation persisted, the patient was admitted to hospital for at least 5 days to decide whether this was due to non‐compliance to diet and/or drug treatment or to secondary failure of therapy" (IO)
UKPDS 34 1998	All‐cause mortality	ND
	Serious adverse events	"Serious adverse events" (IO)
	Health‐related quality of life	—
	Non serious adverse events	—
	Cardiovascular mortality	"Death due to cardiovascular disease is calculated by adding: fatal myocardial infarction, sudden death, fatal stroke, death from peripheral vascular disease" (IO)
	Non‐fatal myocardial infarction	"WHO clinical criteria with associated (IO)
	Non‐fatal stroke	"Major stroke‐stroke with symptoms that persisted for more than one month (ICD 430 to 434.9 and 436)" (IO)
	End‐stage renal disease	"Renal failure dialysis and/or plasma creatinine > 250 mmol/1 not ascribable" (IO)
	Blindness	"Blindness" (IO)
	Severe hypoglycaemia	"Major if third‐party help or medical intervention was necessary" (IO)
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	"Major limb complications‐requiring amputation of digit or limb for any reason (ICD codes 5.845 to 5.848)" (IO)
	Congestive heart failure	Heart failure (IO)
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	"Marked hyperglycaemia again developed" (IO)
Umpierrez 2014	All‐cause mortality	"Deaths" (IO)
	Serious adverse events	"Serious adverse events" (IO)
	Health‐related quality of life	—
	Non serious adverse events	"Adverse events" (SO)
	Cardiovascular mortality	"Fatal CV Event" (AO)
	Non‐fatal myocardial infarction	Acute myocardial infarctione (AO)
	Non‐fatal stroke	Strokee(AO)
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	"Severe hypoglycemia was any episode requiring the assistance of another person to actively administer therapy" (IO)
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	Cardiac failure congestive (AO)
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	"An add‐on re cue therapy was allowed for patients who met prespecified criteria for severe, persistent hyperglycaemia" (IO)
Williams‐Herman 2010	All‐cause mortality	"Deaths" (IO)
	Serious adverse events	"Serious adverse experiences" (IO)
	Health‐related quality of life	—
	Non serious adverse events	"Adverse experiences" (SO)
	Cardiovascular mortality	NDf
	Non‐fatal myocardial infarction	"Acute myocardial infarction"e (IO)
	Non‐fatal stroke	"Cerebrovascular accident"e (IO)
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	"Hypoglycaemia that required assistance (including medical treatment) or exhibited marked severity (i.e. depressed level of consciousness, loss of consciousness or seizure)" (IO)
	Anthropometric measures	BMI; weight (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	—
	Cardiac revascularisation	—
	Peripheral revascularisation	—
	Socioeconomic effects	—
	Intervention failure	"Glibenclamide; from week 0 to 6 glycaemic rescue criteria were FPG > 270 mg/dL, from week 6 to 12 FPG > 240 mg/dL, and from week 12 to 24 FPG > 200 mg/dL; from week 30 the criteria was HbA1c > 8.0%; from week 50 the criteria was HbA1c > 7.5%; participants requiring glycaemic rescue during the study continued treatment until discontinuation from or completion of the study" (IO)
Yamanouchi 2005	All‐cause mortality	NDb
	Serious adverse events	"Major adverse events" (IO)
	Health‐related quality of life	—
	Non serious adverse events	"Adverse events" (SO)
	Cardiovascular mortality	—
	Non‐fatal myocardial infarction	NDb
	Non‐fatal stroke	NDb
	End‐stage renal disease	—
	Blindness	—
	Severe hypoglycaemia	NDb
	Anthropometric measures	BMI (IO)
	Glycaemic control	HbA1c; FPG (IO)
	Lactic acidosis	—
	Amputation of lower extremity	—
	Congestive heart failure	NDb
	Cardiac revascularisation	NDb
	Peripheral revascularisation	NDb
	Socioeconomic effects	—
	Intervention failure	"Treatment failure" (IO)
aIn addition to definition of endpoint measurement, description who measured the outcome (AO: adjudicated outcome measurement; IO: investigator‐assessed outcome measurement; SO: self‐reported outcome measurement) bWe assume the outcome was evaluated but it was not stated explicitly in the full article cThere were no myocardial infarctions throughout the study including non‐fatal dThere were no hypoglycaemic incidents throughout the study including severe hypoglycaemia eCauses of death during the study are known and thus, these events are non‐fatal fCauses of death during the study are known and none were cardiovascular. AEs: adverse events; BMI: body mass index; CV: cardiovascular; FPG: fasting plasma glucose; HbA1c: glycosylated haemoglobin A1c; ICD: International Classification of Diseases and Related Health Problems; ND: not defined; UKPDS: United Kingdom Prospective Diabetes Study.