parallel randomized trial

NCT04093752

A Randomized, Phase 3, Open-label Trial Comparing the Effect of Tirzepatide Once Weekly Versus Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes on Metformin With or Without a Sulfonylurea

Type 2 diabetes (adults)NCT04093752S000909

Design

Randomized: 917
Start year: 2019
Treatment: 40 weeks, follow-up 44 weeks
Countries: Australia, China, India, South Korea (66 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: adults with T2D on metformin with or without sulfonylurea

Conduct and analysis

Blinding: open label
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: hypothetical
Analysis population: modified itt
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Tirzepatide 5 mg subcutaneous once weekly Tirzepatide 5 mg	metformin with or without sulfonylurea; lifestyle: not reported	230	211
A2	Tirzepatide 10 mg subcutaneous once weekly Tirzepatide 10 mg	metformin with or without sulfonylurea; lifestyle: not reported	228	194
A3	Tirzepatide 15 mg subcutaneous once weekly Tirzepatide 15 mg	metformin with or without sulfonylurea; lifestyle: not reported	229	193
A4	Insulin glargine Insulin glargine	metformin with or without sulfonylurea; lifestyle: not reported	230	193

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Tirzepatide 5 mg subcutaneous once weekly A1	Tirzepatide 10 mg subcutaneous once weekly A2	Tirzepatide 15 mg subcutaneous once weekly A3	Insulin glargine A4
age	mean (years)	53.10	53.50	54.30	55.60
age	sd (years)	11.25	11.14	11.65	11.40
asian	n	225	225	226	216
black	n	0	0	0	0
bmi	mean (kg/m2)	28.1	27.7	27.8
bmi	sd (kg/m2)	3.9	3.8	3.8
diabetes duration	mean (years)	7.4	7.9	7.6
diabetes duration	sd (years)	5.9	5.7	5.6
egfr	mean (mL/min/1.73 m2)	102.1	102.0	100.5
egfr	sd (mL/min/1.73 m2)	14.6	14.3	16.0
female	n	96	102	100	102
hba1c	mean (percent)	8.77	8.70	8.67	8.68
hba1c	sd (percent)	0.976	0.955	0.960	0.934
other metformin alone	n	121	121	118
other metformin alone	percent	52.6	53.1	51.5
other race american indian alaska native	n	0	0	0	0
other race multiple	n	0	0	0	0
other race native hawaiian pacific islander	n	2	0	3	0
sbp	mean (mmHg)	129.5	129.2	129.0
sbp	sd (mmHg)	13.8	14.7	13.0
weight	mean (kg)	77.7	76.3	76.2
weight	sd (kg)	14.2	15.0	13.6
white	n	3	3	0	4

Analyses this trial contributes to

Results

99 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

HbA1c change (9 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1 vs A4	md	-1.29 percent		-1.49 to -1.09		hypothetical; modified itt; registry:outcomes
40	A1	change	-2.24 percent	0.070		211	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	md	-1.49 percent		-1.69 to -1.29		hypothetical; modified itt; registry:outcomes
40	A2	change	-2.44 percent	0.073		194	hypothetical; modified itt; registry:outcomes
40	A3	change	-2.53 percent	0.087			hypothetical; modified itt; age:less_than_65; R0007363:Results
40	A3	change	-2.49 percent	0.072		193	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	md	-1.54 percent		-1.74 to -1.34		hypothetical; modified itt; registry:outcomes
40	A3	change	-2.08 percent	0.160			hypothetical; modified itt; age:65_or_more; R0007363:Results
40	A4	change	-0.95 percent	0.073		193	hypothetical; modified itt; registry:outcomes

Body weight change in kilograms (diabetes) (13 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	-5.85 kg	0.509			hypothetical; modified itt; hba1c:8.5_or_less; R0007363:Results
40	A1	change	-5.42 kg	0.385			hypothetical; modified itt; bmi:25_or_more; R0007363:Results
40	A1	change	-5.0 kg	0.32		211	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	md	-6.5 kg		-7.4 to -5.6		hypothetical; modified itt; registry:outcomes
40	A1	change	-4.41 kg	0.447			hypothetical; modified itt; hba1c:more_than_8.5; R0007363:Results
40	A1	change	-3.66 kg	0.714			hypothetical; modified itt; bmi:less_than_25; R0007363:Results
40	A2 vs A4	md	-8.5 kg		-9.5 to -7.6		hypothetical; modified itt; registry:outcomes
40	A2	change	-7.0 kg	0.33		194	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	md	-8.7 kg		-9.6 to -7.7		hypothetical; modified itt; registry:outcomes
40	A3	change	-4.67 kg	0.728			hypothetical; modified itt; age:65_or_more; R0007363:Results
40	A3	change	-7.90 kg	0.393			hypothetical; modified itt; age:less_than_65; R0007363:Results
40	A3	change	-7.2 kg	0.33		193	hypothetical; modified itt; registry:outcomes
40	A4	change	1.5 kg	0.33		194	hypothetical; modified itt; registry:outcomes

HbA1c below 7 percent (7 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1 vs A4	or	14.54	8.94 to 23.64		hypothetical; modified itt; registry:outcomes
40	A1	responders	75.44		228	hypothetical; modified itt; registry:outcomes
40	A2	responders	86.04		222	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	or	28.76	16.72 to 49.49		hypothetical; modified itt; registry:outcomes
40	A3	responders	84.38		224	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	or	25.27	14.88 to 42.95		hypothetical; modified itt; registry:outcomes
40	A4	responders	23.72		215	hypothetical; modified itt; registry:outcomes

Weight loss of 5 percent or more (7 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	responders	55.70		228	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	or	21.89	11.63 to 41.20		hypothetical; modified itt; registry:outcomes
40	A2	responders	71.62		222	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	or	43.79	22.96 to 83.50		hypothetical; modified itt; registry:outcomes
40	A3	responders	74.11		224	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	or	48.41	25.34 to 92.49		hypothetical; modified itt; registry:outcomes
40	A4	responders	5.58		215	hypothetical; modified itt; registry:outcomes

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 230	not stated; safety; registry:adverse_events
A2	events	0 / 228	not stated; safety; registry:adverse_events
A3	events	1 / 229	not stated; safety; registry:adverse_events
A4	events	2 / 220	not stated; safety; registry:adverse_events

Health related quality of life total score (any instrument) (7 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	final	16.0 points	0.27		212	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	md	1.81 points		1.03 to 2.59		hypothetical; modified itt; registry:outcomes
40	A2	final	15.8 points	0.28		200	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	md	1.63 points		0.84 to 2.41		hypothetical; modified itt; registry:outcomes
40	A3	final	15.9 points	0.29		195	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	md	1.68 points		0.89 to 2.47		hypothetical; modified itt; registry:outcomes
40	A4	final	14.2 points	0.28		196	hypothetical; modified itt; registry:outcomes

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	15 / 230	not stated; safety; registry:adverse_events
A2	events	14 / 228	not stated; safety; registry:adverse_events
A3	events	15 / 229	not stated; safety; registry:adverse_events
A4	events	20 / 220	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (8 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	10 / 230	not stated; safety; R0015264:Table 2
A1	events	7 / 230	not stated; safety; R0015264:Table 2
A2	events	30 / 228	not stated; safety; R0015264:Table 2
A2	events	19 / 228	not stated; safety; R0015264:Table 2
A3	events	28 / 229	not stated; safety; R0015264:Table 2
A3	events	19 / 229	not stated; safety; R0015264:Table 2
A3	events	18 / 229	not stated; randomized; registry:flow
A4	events	4 / 230	not stated; randomized; registry:flow

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	46 / 230	not stated; safety; registry:adverse_events
A2	events	75 / 228	not stated; safety; registry:adverse_events
A3	events	73 / 229	not stated; safety; registry:adverse_events
A4	events	5 / 220	not stated; safety; registry:adverse_events

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	21 / 230	not stated; safety; registry:adverse_events
A2	events	34 / 228	not stated; safety; registry:adverse_events
A3	events	29 / 229	not stated; safety; registry:adverse_events
A4	events	3 / 220	not stated; safety; registry:adverse_events

Diarrhea (8 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	77 / 230	not stated; safety; registry:adverse_events
A1	events	0 / 230	not stated; safety; registry:adverse_events
A2	events	103 / 228	not stated; safety; registry:adverse_events
A2	events	1 / 228	not stated; safety; registry:adverse_events
A3	events	101 / 229	not stated; safety; registry:adverse_events
A3	events	0 / 229	not stated; safety; registry:adverse_events
A4	events	0 / 220	not stated; safety; registry:adverse_events
A4	events	3 / 220	not stated; safety; registry:adverse_events

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	12 / 230	not stated; safety; registry:adverse_events
A2	events	17 / 228	not stated; safety; registry:adverse_events
A3	events	23 / 229	not stated; safety; registry:adverse_events
A4	events	3 / 220	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (8 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 230	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	0 / 230	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	1 / 228	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	0 / 228	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	1 / 229	not stated; safety; cholecystitis acute; registry:adverse_events
A3	events	0 / 229	not stated; safety; cholelithiasis; registry:adverse_events
A4	events	0 / 220	not stated; safety; cholelithiasis; registry:adverse_events
A4	events	0 / 220	not stated; safety; cholecystitis acute; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 230	not stated; safety; registry:adverse_events
A2	events	0 / 228	not stated; safety; registry:adverse_events
A3	events	0 / 229	not stated; safety; registry:adverse_events
A4	events	1 / 220	not stated; safety; registry:adverse_events

Thyroid cancer (any) (4 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 230	not stated; safety; papillary thyroid cancer; registry:adverse_events
A2	events	2 / 228	not stated; safety; papillary thyroid cancer; registry:adverse_events
A3	events	0 / 229	not stated; safety; papillary thyroid cancer; registry:adverse_events
A4	events	0 / 220	not stated; safety; papillary thyroid cancer; registry:adverse_events

Intestinal obstruction or ileus (4 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 230	not stated; safety; mechanical ileus; registry:adverse_events
A2	events	1 / 228	not stated; safety; mechanical ileus; registry:adverse_events
A3	events	0 / 229	not stated; safety; mechanical ileus; registry:adverse_events
A4	events	0 / 220	not stated; safety; mechanical ileus; registry:adverse_events