parallel randomized trial

NCT04153929

A Phase II, Randomized, Parallel Group, Dose-finding Study of Subcutaneously Administered BI 456906 for 16 Weeks, Compared With Placebo and Open-label Semaglutide in Patients With Type 2 Diabetes Mellitus.

Type 2 diabetes (adults)NCT04153929S000172

Design

Randomized: 413
Start year: 2020
Treatment: 16 weeks, follow-up 20 weeks
Countries: multinational
Sponsor: Boehringer Ingelheim (industry)
Eligibility: age 18 to 75; HbA1c 7.0 to 10.0 percent; BMI 25 to 50; metformin at least 1000 mg

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: full analysis
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Survodutide 0.3 mg subcutaneous once weekly Survodutide 0.3 mg QW	metformin at least 1000 mg per day; lifestyle: standard	50	50	41
A2	Survodutide 0.9 mg subcutaneous once weekly Survodutide 0.9 mg QW	metformin at least 1000 mg per day; lifestyle: standard	50	50	45
A3	Survodutide 1.8 mg subcutaneous once weekly Survodutide 1.8 mg QW	metformin at least 1000 mg per day; lifestyle: standard	52	52	36
A4	Survodutide 2.7 mg subcutaneous once weekly Survodutide 2.7 mg QW	metformin at least 1000 mg per day; lifestyle: standard	50	50	33
A5	survodutide Survodutide 1.2 mg twice weekly	metformin at least 1000 mg per day; lifestyle: standard	51	51	45
A6	survodutide Survodutide 1.8 mg twice weekly	metformin at least 1000 mg per day; lifestyle: standard	50	49	37
A7	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg QW open label	metformin at least 1000 mg per day; lifestyle: standard	50	50	45
A8	Placebo Placebo	metformin at least 1000 mg per day; lifestyle: standard	60	59	49

Baseline characteristics

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

Characteristic	Statistic	Survodutide 0.3 mg subcutaneous once weekly A1	Survodutide 0.9 mg subcutaneous once weekly A2	Survodutide 1.8 mg subcutaneous once weekly A3	Survodutide 2.7 mg subcutaneous once weekly A4	Survodutide 1.2 mg twice weekly A5	Survodutide 1.8 mg twice weekly A6	Semaglutide 1.0 mg subcutaneous once weekly A7	Placebo A8
age	mean (years)	56.1	58.2	55.3	59.6	58.3	57.7	55.8	57.5
age	sd (years)	10.2	9.6	10.3	8.5	8.8	9.4	10.5	10.5
asian	n	4	5	8	4	5	3	5	8
asian	percent	8.0	10.0	15.4	8.0	9.8	6.1	10.0	13.6
black	n	3	1	2	2	4	3	2	3
black	percent	6.0	2.0	3.8	4.0	7.8	6.1	4.0	5.1
bmi	mean (kg/m2)	33.8	34.9	33.6	34.0	33.0	34.9	33.4	33.4
bmi	sd (kg/m2)	6.1	5.2	5.8	6.8	5.0	7.0	6.1	5.9
diabetes duration	mean (years)	6.1	7.7	7.0	7.9	8.8	7.4	7.9	7.9
diabetes duration	sd (years)	4.7	7.3	5.6	5.7	7.1	5.3	4.7	5.6
female	n	24	22	25	17	24	22	16	28
hba1c	mean (percent)	8.09	7.89	8.14	8.18	8.11	7.97	8.03	8.15
hba1c	sd (percent)	0.76	0.8	0.86	0.97	0.94	0.71	0.82	0.85
hispanic	n	11	8	12	12	10	9	14	15
other race american indian alaska native	n	1	0	0	0	0	1	0	0
other race american indian alaska native	percent	2.0					2.0
other race native hawaiian pacific islander	n	0	0	0	0	0	0	0	1
other race native hawaiian pacific islander	percent								1.7
waist	mean (cm)	110.6	111.5	107.2	110.7	109.0	115.1	108.1	110.4
waist	sd (cm)	12.8	15.6	20.0	16.4	18.2	28.7	13.5	16.5
weight	mean (kg)	97.6	100.1	95.9	96.6	95.0	98.3	96.7	93.0
weight	sd (kg)	19.7	19.8	22.8	22.8	22.1	24.4	20.0	21.0
white	n	42	44	42	43	41	42	43	47
white	percent	84.0	88.0	80.8	86.0	80.4	85.7	86.0	79.7

Results

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

HbA1c change (22 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
16	A1	change	-0.91 percent	0.71		41	not stated; full analysis; registry:outcomes
16	A1	change	-0.91 percent		-1.12 to -0.69	41	not stated; full analysis; R0007239:Results
16	A1 vs A8	md	-0.76 percent		-1.06 to -0.46		not stated; full analysis; registry:outcomes
16	A2	change	-1.46 percent		-1.67 to -1.25	46	not stated; full analysis; R0007239:Results
16	A2	change	-1.37 percent	0.93		46	not stated; full analysis; registry:outcomes
16	A2 vs A8	md	-1.31 percent		-1.6 to -1.01		not stated; full analysis; registry:outcomes
16	A3	change	-1.71 percent		-1.94 to -1.49	36	not stated; full analysis; R0007239:Results
16	A3	change	-1.79 percent	0.92		36	not stated; full analysis; registry:outcomes
16	A3 vs A8	md	-1.56 percent		-1.87 to -1.26		not stated; full analysis; registry:outcomes
16	A4	change	-1.56 percent		-1.79 to -1.32	33	not stated; full analysis; R0007239:Results
16	A4	change	-1.67 percent	0.78		33	not stated; full analysis; registry:outcomes
16	A4 vs A8	md	-1.41 percent		-1.72 to -1.1		not stated; full analysis; registry:outcomes
16	A5	change	-1.63 percent		-1.85 to -1.42	44	not stated; full analysis; R0007239:Results
16	A5	change	-1.68 percent	0.90		44	not stated; full analysis; registry:outcomes
16	A5 vs A8	md	-1.49 percent		-1.78 to -1.19		not stated; full analysis; registry:outcomes
16	A6	change	-1.68 percent		-1.91 to -1.45	36	not stated; full analysis; R0007239:Results
16	A6	change	-1.79 percent	0.76		36	not stated; full analysis; registry:outcomes
16	A6 vs A8	md	-1.53 percent		-1.84 to -1.22		not stated; full analysis; registry:outcomes
16	A7	change	-1.47 percent			45	not stated; full analysis; R0007239:Results
16	A7	change	-1.50 percent	0.84		45	not stated; full analysis; registry:outcomes
16	A8	change	-0.15 percent		-0.35 to 0.05	49	not stated; full analysis; R0007239:Results
16	A8	change	-0.23 percent	0.81		49	not stated; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (17 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
16	A1	change	-1.90 kg	3.12		41	not stated; full analysis; registry:outcomes
16	A1 vs A8	md	-0.66 kg		-2.34 to 1.03		not stated; full analysis; registry:outcomes
16	A2 vs A8	md	-3.28 kg		-4.95 to -1.61		not stated; full analysis; registry:outcomes
16	A2	change	-4.41 kg	4.07		46	not stated; full analysis; registry:outcomes
16	A3	change	-6.31 kg	4.53		36	not stated; full analysis; registry:outcomes
16	A3 vs A8	md	-4.93 kg		-6.62 to -3.23		not stated; full analysis; registry:outcomes
16	A4	change	-6.88 kg	4.41		33	not stated; full analysis; registry:outcomes
16	A4 vs A8	md	-5.76 kg		-7.53 to -4.0		not stated; full analysis; registry:outcomes
16	A5	change	-6.75 kg	6.10		44	not stated; full analysis; registry:outcomes
16	A5 vs A8	md	-5.44 kg		-7.11 to -3.77		not stated; full analysis; registry:outcomes
16	A6	change	-8.4 kg		-9.7 to -7.1	37	not stated; full analysis; R0007239:Results
16	A6	change	-8.88 kg	4.93		37	not stated; full analysis; registry:outcomes
16	A6 vs A8	md	-7.05 kg		-8.79 to -5.31		not stated; full analysis; registry:outcomes
16	A7	change	-5.2 kg		-6.4 to -4.0	45	not stated; full analysis; R0007239:Results
16	A7	change	-5.18 kg	4.52		45	not stated; full analysis; registry:outcomes
16	A7 vs A8	md	-3.85 kg		-5.52 to -2.18		not stated; full analysis; registry:outcomes
16	A8	change	-1.28 kg	3.05		49	not stated; full analysis; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (8 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	1 / 50	not stated; safety; registry:adverse_events
A2	events	1 / 50	not stated; safety; registry:adverse_events
A3	events	3 / 52	not stated; safety; registry:adverse_events
A4	events	2 / 50	not stated; safety; registry:adverse_events
A5	events	0 / 51	not stated; safety; registry:adverse_events
A6	events	3 / 49	not stated; safety; registry:adverse_events
A7	events	4 / 50	not stated; safety; registry:adverse_events
A8	events	2 / 59	not stated; safety; registry:adverse_events

Percent body weight change (17 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
16	A1	percent change	-1.86 percent	2.91		41	not stated; full analysis; registry:outcomes
16	A1 vs A8	md	-1.11 percent		-2.9 to 0.68		not stated; full analysis; registry:outcomes
16	A2	percent change	-4.43 percent	3.92		46	not stated; full analysis; registry:outcomes
16	A2 vs A8	md	-3.79 percent		-5.56 to -2.01		not stated; full analysis; registry:outcomes
16	A3	percent change	-6.6 percent		-7.9 to -5.3	36	not stated; full analysis; R0007239:Results
16	A3	percent change	-6.63 percent	5.13		36	not stated; full analysis; registry:outcomes
16	A3 vs A8	md	-5.61 percent		-7.41 to -3.81		not stated; full analysis; registry:outcomes
16	A4	percent change	-6.68 percent	4.05		33	not stated; full analysis; registry:outcomes
16	A4 vs A8	md	-6.25 percent		-8.12 to -4.38		not stated; full analysis; registry:outcomes
16	A5	percent change	-7.16 percent	6.06		44	not stated; full analysis; registry:outcomes
16	A5 vs A8	md	-6.25 percent		-8.02 to -4.47		not stated; full analysis; registry:outcomes
16	A6	percent change	-8.7 percent		-10.1 to -7.3	37	not stated; full analysis; R0007239:Results
16	A6	percent change	-8.95 percent	5.33		37	not stated; full analysis; registry:outcomes
16	A6 vs A8	md	-7.68 percent		-9.52 to -5.83		not stated; full analysis; registry:outcomes
16	A7	percent change	-5.3 percent		-6.6 to -4.1	45	not stated; full analysis; R0007239:Results
16	A7	percent change	-5.40 percent	4.33		45	not stated; full analysis; registry:outcomes
16	A8	percent change	-1.20 percent	3.52		49	not stated; full analysis; registry:outcomes

Weight loss of 5 percent or more (15 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	responders			4 / 50	not stated; full analysis; R0007239:Table 2
16	A1 vs A8	or	1.22	0.28 to 5.2		not stated; full analysis; R0007239:Table 2
16	A2	responders			19 / 50	not stated; full analysis; R0007239:Table 2
16	A2 vs A8	or	7.92	2.43 to 25.74		not stated; full analysis; R0007239:Table 2
16	A3	responders			22 / 52	not stated; full analysis; R0007239:Table 2
16	A3 vs A8	or	17.68	5.21 to 60.03		not stated; full analysis; R0007239:Table 2
16	A4	responders			23 / 50	not stated; full analysis; R0007239:Table 2
16	A4 vs A8	or	25.87	7.31 to 91.55		not stated; full analysis; R0007239:Table 2
16	A5	responders			29 / 51	not stated; full analysis; R0007239:Table 2
16	A5 vs A8	or	21.75	6.57 to 72.04		not stated; full analysis; R0007239:Table 2
16	A6	responders			28 / 49	not stated; full analysis; R0007239:Table 2
16	A6 vs A8	or	35.0	9.84 to 124.47		not stated; full analysis; R0007239:Table 2
16	A7	responders			19 / 50	not stated; full analysis; R0007239:Table 2
16	A7 vs A8	or	8.22	2.52 to 26.79		not stated; full analysis; R0007239:Table 2
16	A8	responders			4 / 59	not stated; full analysis; R0007239:Table 2

Weight loss of 10 percent or more (22 lines; O11B)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	responders			1 / 50	not stated; full analysis; R0007239:Table 2
16	A1 vs A8	or	3.67	0.14 to 95.68		not stated; full analysis; R0007239:Table 2
16	A1 vs A8	or	3.67	0.14 to 95.73		not stated; full analysis; registry:outcomes
16	A2	responders			3 / 50	not stated; full analysis; R0007239:Table 2
16	A2 vs A8	or	7.97	0.39 to 163.48		not stated; full analysis; R0007239:Table 2
16	A2 vs A8	or	7.97	0.39 to 163.56		not stated; full analysis; registry:outcomes
16	A3	responders			7 / 52	not stated; full analysis; R0007239:Table 2
16	A3 vs A8	or	25.17	1.35 to 470.86		not stated; full analysis; R0007239:Table 2
16	A3 vs A8	or	25.17	1.35 to 471.09		not stated; full analysis; registry:outcomes
16	A4	responders			8 / 50	not stated; full analysis; R0007239:Table 2
16	A4 vs A8	or	33.0	1.78 to 613.2		not stated; full analysis; R0007239:Table 2
16	A4 vs A8	or	33.01	1.78 to 613.51		not stated; full analysis; registry:outcomes
16	A5	responders			13 / 51	not stated; full analysis; R0007239:Table 2
16	A5 vs A8	or	42.43	2.37 to 761.05		not stated; full analysis; R0007239:Table 2
16	A5 vs A8	or	42.44	2.37 to 761.44		not stated; full analysis; registry:outcomes
16	A6	responders			17 / 49	not stated; full analysis; R0007239:Table 2
16	A6 vs A8	or	84.51			not stated; full analysis; R0007239:Table 2
16	A6 vs A8	or	84.53	4.71 to 999		not stated; full analysis; registry:outcomes
16	A7	responders			8 / 50	not stated; full analysis; R0007239:Table 2
16	A7 vs A8	or	22.44	1.22 to 413.13		not stated; full analysis; R0007239:Table 2
16	A7 vs A8	or	22.44	1.22 to 413.33		not stated; full analysis; registry:outcomes
16	A8	responders			0 / 59	not stated; full analysis; R0007239:Table 2

All cause mortality (8 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 50	not stated; safety; registry:adverse_events
A2	events	0 / 50	not stated; safety; registry:adverse_events
A3	events	0 / 52	not stated; safety; registry:adverse_events
A4	events	0 / 50	not stated; safety; registry:adverse_events
A5	events	0 / 51	not stated; safety; registry:adverse_events
A6	events	0 / 49	not stated; safety; registry:adverse_events
A7	events	0 / 50	not stated; safety; registry:adverse_events
A8	events	0 / 59	not stated; safety; registry:adverse_events

Serious adverse events (8 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	1 / 50	not stated; safety; R0007239:Table 3
A2	events	4 / 50	not stated; safety; R0007239:Table 3
A3	events	3 / 52	not stated; safety; R0007239:Table 3
A4	events	2 / 50	not stated; safety; R0007239:Table 3
A5	events	1 / 51	not stated; safety; R0007239:Table 3
A6	events	0 / 49	not stated; safety; R0007239:Table 3
A7	events	0 / 50	not stated; safety; R0007239:Table 3
A8	events	3 / 59	not stated; safety; R0007239:Table 3

Discontinuation due to adverse events (8 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	5 / 50	not stated; safety; R0007239:Table 3
A2	events	5 / 50	not stated; safety; R0007239:Table 3
A3	events	11 / 52	not stated; safety; R0007239:Table 3
A4	events	15 / 50	not stated; safety; R0007239:Table 3
A5	events	4 / 51	not stated; safety; R0007239:Table 3
A6	events	8 / 49	not stated; safety; R0007239:Table 3
A7	events	2 / 50	not stated; safety; R0007239:Table 3
A8	events	3 / 59	not stated; safety; R0007239:Table 3

Nausea (16 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	10 / 50	not stated; safety; R0007239:Table 3
A1	events	10 / 50	not stated; safety; registry:adverse_events
A2	events	14 / 50	not stated; safety; registry:adverse_events
A2	events	13 / 50	not stated; safety; R0007239:Table 3
A3	events	24 / 52	not stated; safety; R0007239:Table 3
A3	events	25 / 52	not stated; safety; registry:adverse_events
A4	events	20 / 50	not stated; safety; R0007239:Table 3
A4	events	23 / 50	not stated; safety; registry:adverse_events
A5	events	14 / 51	not stated; safety; R0007239:Table 3
A5	events	14 / 51	not stated; safety; registry:adverse_events
A6	events	22 / 49	not stated; safety; R0007239:Table 3
A6	events	23 / 49	not stated; safety; registry:adverse_events
A7	events	6 / 50	not stated; safety; R0007239:Table 3
A7	events	6 / 50	not stated; safety; registry:adverse_events
A8	events	5 / 59	not stated; safety; R0007239:Table 3
A8	events	5 / 59	not stated; safety; registry:adverse_events

Vomiting (24 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	6 / 50	not stated; safety; R0007239:Table 3
A1	events	7 / 50	not stated; safety; registry:adverse_events
A1	events	1 / 50	not stated; safety; registry:adverse_events
A2	events	7 / 50	not stated; safety; R0007239:Table 3
A2	events	9 / 50	not stated; safety; registry:adverse_events
A2	events	0 / 50	not stated; safety; registry:adverse_events
A3	events	12 / 52	not stated; safety; R0007239:Table 3
A3	events	12 / 52	not stated; safety; registry:adverse_events
A3	events	0 / 52	not stated; safety; registry:adverse_events
A4	events	13 / 50	not stated; safety; R0007239:Table 3
A4	events	13 / 50	not stated; safety; registry:adverse_events
A4	events	0 / 50	not stated; safety; registry:adverse_events
A5	events	0 / 51	not stated; safety; registry:adverse_events
A5	events	6 / 51	not stated; safety; R0007239:Table 3
A5	events	6 / 51	not stated; safety; registry:adverse_events
A6	events	11 / 49	not stated; safety; registry:adverse_events
A6	events	10 / 49	not stated; safety; R0007239:Table 3
A6	events	0 / 49	not stated; safety; registry:adverse_events
A7	events	2 / 50	not stated; safety; R0007239:Table 3
A7	events	2 / 50	not stated; safety; registry:adverse_events
A7	events	0 / 50	not stated; safety; registry:adverse_events
A8	events	1 / 59	not stated; safety; R0007239:Table 3
A8	events	3 / 59	not stated; safety; registry:adverse_events
A8	events	0 / 59	not stated; safety; registry:adverse_events

Diarrhea (24 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	12 / 50	not stated; safety; registry:adverse_events
A1	events	0 / 50	not stated; safety; registry:adverse_events
A1	events	11 / 50	not stated; safety; R0007239:Table 3
A2	events	5 / 50	not stated; safety; R0007239:Table 3
A2	events	8 / 50	not stated; safety; registry:adverse_events
A2	events	0 / 50	not stated; safety; registry:adverse_events
A3	events	8 / 52	not stated; safety; R0007239:Table 3
A3	events	9 / 52	not stated; safety; registry:adverse_events
A3	events	0 / 52	not stated; safety; registry:adverse_events
A4	events	7 / 50	not stated; safety; R0007239:Table 3
A4	events	7 / 50	not stated; safety; registry:adverse_events
A4	events	1 / 50	not stated; safety; registry:adverse_events
A5	events	8 / 51	not stated; safety; R0007239:Table 3
A5	events	8 / 51	not stated; safety; registry:adverse_events
A5	events	0 / 51	not stated; safety; registry:adverse_events
A6	events	11 / 49	not stated; safety; registry:adverse_events
A6	events	9 / 49	not stated; safety; R0007239:Table 3
A6	events	0 / 49	not stated; safety; registry:adverse_events
A7	events	4 / 50	not stated; safety; R0007239:Table 3
A7	events	5 / 50	not stated; safety; registry:adverse_events
A7	events	0 / 50	not stated; safety; registry:adverse_events
A8	events	5 / 59	not stated; safety; R0007239:Table 3
A8	events	7 / 59	not stated; safety; registry:adverse_events
A8	events	0 / 59	not stated; safety; registry:adverse_events

Constipation (8 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	3 / 50	not stated; safety; registry:adverse_events
A2	events	2 / 50	not stated; safety; registry:adverse_events
A3	events	7 / 52	not stated; safety; registry:adverse_events
A4	events	7 / 50	not stated; safety; registry:adverse_events
A5	events	8 / 51	not stated; safety; registry:adverse_events
A6	events	5 / 49	not stated; safety; registry:adverse_events
A7	events	3 / 50	not stated; safety; registry:adverse_events
A8	events	0 / 59	not stated; safety; registry:adverse_events

Discontinuation due to gastrointestinal adverse events (2 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A7	events				0 / 50	not stated; safety; R0007239:Results
	A8	events				1 / 59	not stated; safety; R0007239:Results

Gallbladder and biliary disease (8 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 50	not stated; safety; cholecystitis; registry:adverse_events
A2	events	0 / 50	not stated; safety; cholecystitis; registry:adverse_events
A3	events	0 / 52	not stated; safety; cholecystitis; registry:adverse_events
A4	events	0 / 50	not stated; safety; cholecystitis; registry:adverse_events
A5	events	0 / 51	not stated; safety; cholecystitis; registry:adverse_events
A6	events	0 / 49	not stated; safety; cholecystitis; registry:adverse_events
A7	events	0 / 50	not stated; safety; cholecystitis; registry:adverse_events
A8	events	1 / 59	not stated; safety; cholecystitis; registry:adverse_events