Descriptive only

Thyroid cancer (any)

Type 2 diabetes (adults)

longest follow-upRecorded harmsDoses of a drug pooledHazard ratio (from event counts)

Randomized trials

Treatments

37,707

Participants

Events

In plain language

No network meta-analysis was fitted here. The protocol requires at least two trials forming a connected network; this outcome has 31 trials. The trial data below are shown as reported.

Network of trials

Each circle is a treatment; each line joins treatments that were randomized against each other in at least one trial.

Node area shows participants; line width shows trials comparing two treatments directly. Blue: GLP-1 receptor agonist containing treatments; grey: comparators. Hover over or tab to a node or line for details.

Comparability of the trials

Checked across designs (the set of treatments each trial compares) for eligibility, outcome definition and assessment, and the baseline factors above. Flags point to possible intransitivity; notes describe variation that is not tied to design.

NoteOutcome assessment, time point: selected time points span 5 to 365.26 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 2, modified_itt 2, other 1, randomized 2, randomized;safety 1, safety 23
NoteOutcome assessment, definition: mixed: hypoglycemia requiring medical assistance 1, investigator suspected pancreatitis 1, level 3 severe hypoglycemia 1, major, unable to self treat 1, malignant thyroid neoplasms 2, minor (symptomatic, glucose below 54 mg/dL) or major hypoglycemia 1, No severe or below 3 mmol/L hypoglycemia over whole 52 week study 1, not stated 17, primary MACE: serious cardiovascular death, myocardial infarction or stroke, defined retrospectively 1, severe hypoglycemia by ADA classification 1, Severe hypoglycemia needing another person to give carbohydrate, glucagon or other measures (protocol) 1, severe hypoglycemic events, adverse event of special interest 1, severe symptomatic hypoglycemia needing assistance 1, severe, needing assistance of another person 1
NoteOutcome assessment, adjudicated: mixed: no 4, not stated 20, yes 7
NoteOutcome assessment, proportion method: mixed: not stated 30, observed 1
NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 27, treatment_policy 2, while_on_treatment 2
NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 1, not stated 28, treatment_policy 2
NoteRisk of bias, blinding: mixed: double_blind 19, open_label 10, single_blind 2
NoteRisk of bias, funding: mixed: industry 30, non_industry 1
NoteData handling, input conversions: arms_combined 14, printed_denominator 6

Comparability items per trial
Trial	analysis set	time weeks	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	funding	start year	Eligibility
NCT03131687	safety	30	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2017	age 18 to 75; T2D at least 6 months; HbA1c 7.0 to 10.5%; BMI 23 to 50; diet and exercise or metformin
NCT00838916	safety	52	not stated	not stated	yes	not stated	not stated	not stated	open_label	industry	2009	age 18 or older, HbA1c 7.0 to 10.0 percent, BMI 20 to 45, creatinine clearance above 60
SURPASS-6	safety	56	not stated	not stated	not stated	not stated	while_on_treatment	not stated	open_label	industry	2020	adults 18 or older; HbA1c 7.5 to 11 percent; BMI 23 to 45; basal insulin at least 30 U/day with or without up to 2 oral drugs
NCT04965506	safety	24	investigator suspected pancreatitis	not stated	no	not stated	not stated	not stated	double_blind	industry	2021	age 18 to 75; HbA1c 7.0 to 10.5 percent; BMI 20 to under 40; diet or metformin
REWIND	randomized	365.26	Severe hypoglycemia needing another person to give carbohydrate, glucagon or other measures (protocol)	not stated	not stated	not stated	treatment_policy	not stated	double_blind	industry	2011	age 50 or older with T2D; HbA1c 9.5 percent or less; BMI 23 or more; CV disease or risk factors
DUAL™IV	safety	27	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2012	adults 18 or older; HbA1c 7.0 to 9.0 percent; BMI 40 or less; SU with or without metformin; insulin and GLP-1 RA naive
PB119	safety	24	No severe or below 3 mmol/L hypoglycemia over whole 52 week study	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2020	age 18 to 75; HbA1c 7.5 to 11.0 at screening and 7.0 to 10.5 at randomization; BMI 18.5 to 40; eGFR 60 or more; drug naive
PIONEER 10	safety	57	not stated	not stated	yes	not stated	while_on_treatment	treatment_policy	single_blind	industry	2017	Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
AWARD-7	safety	56	not stated	not stated	not stated	not stated	treatment_policy	treatment_policy	single_blind	industry	2012	adults with T2D and CKD stage 3 to 4 (eGFR 15 to below 60); HbA1c 7.5 to 10.5 percent on insulin; maximal ACEI or ARB; BMI 23 to 45
NCT01584232	safety	26	severe, needing assistance of another person	not stated	not stated	not stated	not stated	hypothetical	open_label	industry	2012	Japanese adults 20 years or older; BMI 18.5 to less than 35 kg/m2; HbA1c 7.0 to 10.0 percent; on sulfonylurea and/or biguanide
NCT00765817	full_analysis	30	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2008	adults 18 or older; insulin glargine 20 U/d or more alone or with metformin or pioglitazone; HbA1c 7.1 to 10.5 percent; BMI 45 or less
NCT01029886	modified_itt	26	primary MACE: serious cardiovascular death, myocardial infarction or stroke, defined retrospectively	not stated	no	observed	not stated	not stated	open_label	industry	2010	adults 18 or older with type 2 diabetes on oral agents, HbA1c 7.1 to 11.0 percent, BMI 45 or less
GETGOAL-L-ASIA	safety	24	severe symptomatic hypoglycemia needing assistance	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2009	age 25 to 81; type 2 diabetes at least 1 year; stable basal insulin at least 10 U/day with or without sulfonylurea; HbA1c 7 to 10 percent
NCT00849017	safety	52	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2009	age 18 or older; HbA1c 7.0 to 10.0 percent; BMI 20 to 45; diet and exercise only
AWARD-CHN1	safety	30.29	not stated	not stated	yes	not stated	not stated	not stated	double_blind	industry	2012	age 18 or older; BMI 19 to 35 kg/m2; HbA1c 7.0 to 10.5 percent OAM naive or 6.5 to 10.0 percent on OAM monotherapy
NCT02465515	safety	140.89	severe hypoglycemic events, adverse event of special interest	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2015	type 2 diabetes with established cardiovascular disease
DURATION-NEO-2	safety	28	minor (symptomatic, glucose below 54 mg/dL) or major hypoglycemia	not stated	not stated	not stated	not stated	not stated	open_label	industry	2013	age 18 or older; HbA1c 7.1 to 11.0 percent; BMI 45 or lower; metformin 1500 mg or more
DUALTM IX	safety	27	not stated	not stated	not stated	not stated	not stated	not stated	open_label	industry	2016	adults; insulin naive type 2 diabetes on SGLT2 inhibitor with or without other oral drugs; HbA1c 7.0 to 11.0 percent; BMI 20 to 40
SOLID-DKD	safety	18	level 3 severe hypoglycemia	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2024	age 18 to 75; T2D with UACR 300 to below 3000 mg/g; eGFR 30 or more; HbA1c 6.5 to 10; BMI 20 to 40
PIONEER 6	full_analysis	87	malignant thyroid neoplasms	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2017	T2D; age 50 or more with CVD or CKD, or 60 or more with CV risk factors
DUAL™ II China	safety	30	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2017	age 18 or older; BMI 24 or higher; HbA1c 7.5 or higher; basal insulin 20 to 50 U plus metformin
PIONEER 11	safety	31	not stated	not stated	yes	not stated	not stated	not stated	double_blind	industry	2019	age 18 or older; HbA1c 7.0 to 10.0 percent at screening, 7.0 to 9.5 at randomization; no glucose lowering drugs; eGFR 60 or more
SUSTAIN™ 5	safety	35	not stated	not stated	yes	not stated	not stated	not stated	double_blind	industry	2014	age 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; stable basal insulin with or without metformin; eGFR 30 or more
SUSTAIN™ 6	randomized	109	malignant thyroid neoplasms	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2013	T2D HbA1c 7.0 or more; age 50 or more with CVD, CHF or CKD stage 3 or more, or age 60 or more with CV risk factor
DUAL™ I Japan	randomized;safety	53	not stated	not stated	yes	not stated	not stated	not stated	open_label	industry	2015	Japanese adults 20 or older; HbA1c 7.0 to 11.0 percent; BMI at least 20; insulin naive on one oral drug
SUSTAIN™	safety	35	severe hypoglycemia by ADA classification	not stated	not stated	not stated	not stated	not stated	open_label	industry	2014	Japanese; age 20 or older; HbA1c 6.5 to 9.5 percent on one OAD or 7.0 to 10.5 percent on diet and exercise
NCT03311724	modified_itt	16	not stated	not stated	yes	not stated	not stated	not stated	double_blind	industry	2017	age 18 to 75; T2D at least 6 months; HbA1c 7.0 to 10.5%; BMI 23 to 45; diet or stable metformin
NCT04466904	safety	20	not stated	not stated	no	not stated	not stated	not stated	double_blind	industry	2020	age 18 to 75; T2D on diet and exercise or stable metformin; HbA1c 7.5 to 11.0 percent; BMI 20 to 35
NCT00700817	other	52	major, unable to self treat	not stated	not stated	not stated	not stated	not stated	open_label	industry	2008	age 18 to 80; HbA1c 7.5 to 10%; BMI 45 or less; metformin 1500 mg/day or more for 3 months
NCT06256523	safety	29	not stated	not stated	no	not stated	not stated	not stated	double_blind	industry	2022	age 18 to 65; HbA1c 7.0 to 10.0 percent; BMI 18.5 to 35; eGFR 60 or more
S003079	safety	5	hypoglycemia requiring medical assistance	not stated	not stated	not stated	not stated	not stated	open_label	non_industry	2010	age 18 to 80, HbA1c 7.5 to 12 percent, BMI 21 to 35, T2D at least 6 months

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the hazard ratio (from event counts) on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.

Trial data entering this analysis
Trial	Arm	Treatment	Week	Data	Events / N	Flags	Source
NCT03131687	A1	PLACEBO	30	arm, events	0 / 51		R0016215:Results
NCT03131687	A2+A3+A4+A5	TIRZ_SC	30	arm, events	0 / 213	arms_combined	R0016215:Results
NCT03131687	A6	DULA_SC	30	arm, events	0 / 54		R0016215:Results
NCT00838916	A1	ALBI_SC	52	arm, events	0 / 516		R0025374:p6
NCT00838916	A2	INS_GLARGINE	52	arm, events	0 / 263		R0025374:p6
SURPASS-6	A1+A2+A3	TIRZ_SC	56	arm, events	0 / 717	arms_combined	R0009666:Results
SURPASS-6	A4	INS_LISPRO	56	arm, events	0 / 711		R0009666:Results
NCT04965506	A1+A2+A3	MAZD_SC	24	arm, events	0 / 149	arms_combined	R0012443:Results
NCT04965506	A4	DULA_SC	24	arm, events	0 / 50		R0012443:Results
NCT04965506	A5	PLACEBO	24	arm, events	0 / 51		R0012443:Results
REWIND	A1	PLACEBO	365.26	arm, events	3 / 4,952		R0018537:Table 3
REWIND	A2	DULA_SC	365.26	arm, events	7 / 4,949		R0018537:Table 3
DUAL™IV	A1	IDEGLIRA_SC	27	arm, events	0 / 289		R0015199:Results
DUAL™IV	A2	PLACEBO	27	arm, events	0 / 146		R0015199:Results
PB119	A1	VISEPE_SC	24	arm, events	0 / 137		R0011471:Results
PB119	A2	PLACEBO	24	arm, events	0 / 136		R0011471:Results
PIONEER 10	A1+A2+A3	SEMA_PO	57	arm, events	0 / 393	arms_combined	R0018421:Table 2
PIONEER 10	A4	DULA_SC	57	arm, events	0 / 65		R0018421:Table 2
AWARD-7	A1	INS_GLARGINE	56	arm, events	0 / 194		R0017387:Supplement Results
AWARD-7	A2+A3	DULA_SC	56	arm, events	0 / 383	arms_combined	R0017387:Supplement Results
NCT01584232	A1	DULA_SC	26	arm, events	0 / 181		R0016159:Results
NCT01584232	A2	INS_GLARGINE	26	arm, events	0 / 180		R0016159:Results
NCT00765817	A1	EXEN_SC	30	arm, events	0 / 138		R0027069:Results
NCT00765817	A2	PLACEBO	30	arm, events	0 / 123		R0027069:Results
NCT01029886	A1	EXENER_SC	26	arm, events	0 / 461		R0011287:Results
NCT01029886	A2	LIRA_SC	26	arm, events	0 / 451		R0011287:Results
GETGOAL-L-ASIA	A1	LIXI_SC	24	arm, events	0 / 154		R0022626:Results
GETGOAL-L-ASIA	A2	PLACEBO	24	arm, events	0 / 157		R0022626:Results
NCT00849017	A1	PLACEBO	52	arm, events	0 / 105		R0022386:Results
NCT00849017	A2+A3	ALBI_SC	52	arm, events	0 / 204	arms_combined	R0022386:Results
AWARD-CHN1	A1+A2	DULA_SC	30.29	arm, events	0 / 492	arms_combined	R0014229:Results
AWARD-CHN1	A3	GLIMEPIRIDE	30.29	arm, events	0 / 245		R0014229:Results
NCT02465515	A1	PLACEBO	140.89	arm, events	0 / 4,732		registry:outcomes
NCT02465515	A2	ALBI_SC	140.89	arm, events	0 / 4,731		registry:outcomes
DURATION-NEO-2	A1	EXENER_SC	28	arm, events	0 / 182		R0010641:Table 3
DURATION-NEO-2	A2	SITAGLIPTIN	28	arm, events	0 / 122		R0010641:Table 3
DURATION-NEO-2	A3	PLACEBO	28	arm, events	0 / 61		R0010641:Table 3
DUALTM IX	A1	IDEGLIRA_SC	27	arm, events	0 / 210		R0014323:Results
DUALTM IX	A2	INS_GLARGINE	27	arm, events	0 / 210		R0014323:Results
SOLID-DKD	A1+A2	HRS7535_PO	18	arm, events	0 / 187	arms_combined	R0004355:Table 2
SOLID-DKD	A3	PLACEBO	18	arm, events	0 / 94		R0004355:Table 2
PIONEER 6	A1	SEMA_PO	87	arm, events	2 / 1,591		R0000453:Table 1
PIONEER 6	A2	PLACEBO	87	arm, events	0 / 1,592		R0000453:Table 1
DUAL™ II China	A1	IDEGLIRA_SC	30	arm, events	0 / 302		R0012135:Results
DUAL™ II China	A2	INS_DEGLUDEC	30	arm, events	0 / 151		R0012135:Results
PIONEER 11	A1+A2+A3	SEMA_PO	31	arm, events	1 / 390	arms_combined	R0019663:Supplement Table 6
PIONEER 11	A4	PLACEBO	31	arm, events	0 / 131		R0019663:Supplement Table 6
SUSTAIN™ 5	A1+A2	SEMA_SC	35	arm, events	0 / 264	arms_combined	R0012671:Results
SUSTAIN™ 5	A3	PLACEBO	35	arm, events	0 / 133		R0012671:Results
SUSTAIN™ 6	A5	SEMA_SC	109	arm, events	1 / 1,648	printed_denominator	R0000453:Table 1
SUSTAIN™ 6	A6	PLACEBO	109	arm, events	1 / 1,649	printed_denominator	R0000453:Table 1
DUAL™ I Japan	A1	IDEGLIRA_SC	53	arm, events	0 / 275		R0014857:Results
DUAL™ I Japan	A2	INS_DEGLUDEC	53	arm, events	0 / 271		R0014857:Results
DUAL™ I Japan	A3	LIRA_SC	53	arm, events	0 / 273		R0014857:Results
SUSTAIN™	A1+A2	SEMA_SC	35	arm, events	0 / 205	arms_combined	R0014736:Results
SUSTAIN™	A3	SITAGLIPTIN	35	arm, events	0 / 103		R0014736:Results
NCT03311724	A1	PLACEBO	16	arm, events	0 / 26		R0010282:Results
NCT03311724	A2+A3+A4	TIRZ_SC	16	arm, events	0 / 85	arms_combined	R0010282:Results
NCT04466904	A1+A2+A3	MAZD_SC	20	arm, events	0 / 24	arms_combined	R0009340:Results
NCT04466904	A4	DULA_SC	20	arm, events	0 / 6	printed_denominator	R0009340:Results
NCT04466904	A5	PLACEBO	20	arm, events	0 / 12	printed_denominator	R0009340:Results
NCT00700817	A1+A2	LIRA_SC	52	arm, events	0 / 446	arms_combined	R0024199:Results
NCT00700817	A3	SITAGLIPTIN	52	arm, events	0 / 219		R0024199:Results
NCT06256523	A1	BOFANG_SC	29	arm, events	0 / 27	printed_denominator	R0002476:Results
NCT06256523	A2	PLACEBO	29	arm, events	0 / 9	printed_denominator	R0002476:Results
S003079	A1	EXEN_SC	5	arm, events	0 / 18		R0025923:Results
S003079	A2	STANDARD_CARE	5	arm, events	0 / 18		R0025923:Results

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