Descriptive only

Medullary thyroid carcinoma

Type 2 diabetes (adults)

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

Randomized trials

Treatments

23,538

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 32 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 1, modified_itt 3, other 1, randomized 1, randomized;safety 1, safety 25
NoteOutcome assessment, definition: mixed: ADA severe hypoglycemia 1, hypoglycemia requiring medical assistance 1, investigator suspected pancreatitis 1, level 3 severe hypoglycemia 1, major, unable to self treat 1, minor (symptomatic, glucose below 54 mg/dL) or major hypoglycemia 1, not stated 20, 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 hypoglycemia, subject unable to treat self 1, severe symptomatic hypoglycemia needing assistance 1, severe, needing assistance of another person 1
NoteOutcome assessment, adjudicated: mixed: no 5, not stated 20, yes 7
NoteOutcome assessment, proportion method: mixed: not stated 31, observed 1
NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 28, treatment_policy 2, while_on_treatment 2
NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 1, not stated 29, treatment_policy 2
NoteRisk of bias, blinding: mixed: double_blind 19, open_label 11, single_blind 2
NoteRisk of bias, funding: mixed: industry 31, non_industry 1
NoteData handling, input conversions: arms_combined 17, printed_denominator 5

Comparability items per trial
Trial	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	funding	start year	Eligibility
NCT06256523	29	safety	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
NCT03131687	30	safety	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	52	safety	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	56	safety	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	24	safety	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	365.26	randomized	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	27	safety	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
PIONEER 10	57	safety	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	56	safety	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	26	safety	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	30	full_analysis	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	26	modified_itt	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
S002947	25	safety	not stated	not stated	no	not stated	not stated	not stated	double_blind	industry	2021	age 18 to 65; HbA1c 7.0 to 10.5 percent; BMI 20 to 35; diet or one oral agent washed out
S003079	5	safety	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
GETGOAL-L-ASIA	24	safety	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	52	safety	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
NCT01617434	27	safety	severe hypoglycemia, subject unable to treat self	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2012	age 18 to 80; HbA1c 7.0 to 10.0 percent; BMI 20 to 45; basal insulin analogue 20 U or more with or without metformin
AWARD-CHN1	30.29	safety	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
AWARD-8	24	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2013	age 18 or older; BMI up to 45; HbA1c 7.5 to 9.5 percent on sulfonylurea at least half maximal dose
DURATION-NEO-2	28	safety	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	27	safety	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	18	safety	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
SUSTAIN™	62	safety	ADA severe hypoglycemia	not stated	not stated	not stated	not stated	not stated	open_label	industry	2014	Japanese adults 20 or older; HbA1c 7.0 to 10.5 percent; diet and exercise or OAD monotherapy; eGFR 30 or more
DUAL™ II China	30	safety	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	31	safety	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	35	safety	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
DUAL™ I Japan	53	randomized;safety	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™	35	safety	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
GETGOAL-M	24	safety	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2008	type 2 diabetes on metformin 1.5 g/day or more for 3 months; HbA1c 7 to 10 percent; FPG 13.9 mmol/L or less
NCT03311724	16	modified_itt	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	20	safety	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	52	other	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

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	0 / 4,952		R0018537:Table 3
REWIND	A2	DULA_SC	365.26	arm, events	0 / 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
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
NCT01617434	A1	LIRA_SC	27	arm, events	0 / 226		R0026247:Results
NCT01617434	A2	PLACEBO	27	arm, events	0 / 225		R0026247: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
AWARD-8	A1	DULA_SC	24	arm, events	0 / 240		R0016038:Results
AWARD-8	A2	PLACEBO	24	arm, events	0 / 60		R0016038:Results
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
SUSTAIN™	A1+A2	SEMA_SC	62	arm, events	0 / 480	arms_combined	R0025024:Results
SUSTAIN™	A3	OTHER_ACTIVE_additional_OAD	62	arm, events	0 / 121		R0025024:Results
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+A3	SEMA_PO	31	arm, events	0 / 260	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
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
GETGOAL-M	A1+A2	LIXI_SC	24	arm, events	0 / 510	arms_combined	R0025872:Results
GETGOAL-M	A3	PLACEBO	24	arm, events	0 / 170	printed_denominator	R0025872: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
S002947	A1+A2+A3	ECNO_SC	25	arm, events	0 / 109	arms_combined	R0006482:Results
S002947	A4	PLACEBO	25	arm, events	0 / 36		R0006482: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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