parallel randomized trial

NCT05486065

Investigation of Once-weekly Semaglutide S.C. Dose-Response in Patients With Type 2 Diabetes and Overweight - a Participant- and Investigator-blinded and Sponsor Open-label Study

Type 2 diabetes (adults)NCT05486065S001555

Design

Randomized: 245
Start year: 2022
Treatment: 40 weeks, follow-up 49 weeks
Countries: Greece, Hungary, Poland, United States (75 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 to 64; HbA1c 7.0 to 10.5; BMI 27 or more; on metformin

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: multiple imputation, jump to reference

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 2.0 mg subcutaneous once weekly Semaglutide 2 mg	metformin; lifestyle: not reported	61	61	52
A2	Semaglutide 8 mg injection once weekly Semaglutide 8 mg	metformin; lifestyle: not reported	62	62	42
A3	Semaglutide 16 mg injection once weekly Semaglutide 16 mg	metformin; lifestyle: not reported	62	62	43
A4	Placebo Placebo (pooled)	metformin; lifestyle: not reported	60	60	44

Baseline characteristics

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

Characteristic	Statistic	Semaglutide 2.0 mg subcutaneous once weekly A1	Semaglutide 8 mg injection once weekly A2	Semaglutide 16 mg injection once weekly A3	Placebo A4
age	mean (years)	52.3	53.7	52.9	52.1
age	sd (years)	7.6	7.5	8.6	9.5
asian	n	1	1	0	1
asian	percent	2	2		2
black	n	6	11	4	4
black	percent	10	18	6	7
bmi: 35 or more	n	40	41	37	33
bmi: 35 or more	percent	66	66	60	55
bmi	mean (kg/m2)	37.0	37.6	38.6	37.4
bmi	sd (kg/m2)	5.8	6.4	7.8	6.9
diabetes duration	mean (years)	6.1	7.7	7.6	6.4
diabetes duration	sd (years)	4.7	7.7	5.5	4.3
established cvd: coronary artery disease	n	1	1	2	2
established cvd: coronary artery disease	percent	2	2	3	3
female	n	27	33	25	35
female	percent	44	53	40	58
hba1c	mean (percent)	8.4	8.3	8.3	8.4
hba1c	sd (percent)	1.0	1.0	0.9	1.0
hispanic	n	9	8	9	13
hispanic	percent	15	13	15	22
other race other	n	0	1	2	0
other race other	percent		2	3
sbp	mean (mmHg)	130	129	133	130
sbp	sd (mmHg)	15	14	11	13
waist	mean (cm)	119.2	119.1	123.2	115.0
waist	sd (cm)	19.4	14.4	20.3	18.4
weight	mean (kg)	109.6	109.8	113.9	105.2
weight	sd (kg)	21.6	20.6	27.8	23.4
white	n	54	49	56	55
white	percent	89	79	90	92

Analyses this trial contributes to

Results

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

HbA1c change (24 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	-1.9 percent			39	hypothetical; full analysis; R0005510:Results
40	A1	change	-1.9 percent	1.1		56	not stated; full analysis; registry:outcomes
40	A1	change	-1.8 percent			56	treatment policy; full analysis; R0005510:Results
40	A1 vs A4	md	-0.8 percent		-1.3 to -0.4		treatment policy; full analysis; R0005510:Figure 1
40	A1 vs A4	md	-2.0 percent		-2.9 to -1.1		hypothetical; full analysis; R0005510:Figure 1
40	A2 vs A4	md	-2.3 percent		-3.2 to -1.4		hypothetical; full analysis; R0005510:Figure 1
40	A2	change	-1.8 percent	1.5		57	not stated; full analysis; registry:outcomes
40	A2	change	-2.2 percent			28	hypothetical; full analysis; R0005510:Results
40	A2 vs A1	md	-0.3 percent		-0.7 to 0.2		hypothetical; full analysis; R0005510:Figure 1
40	A2	change	-1.8 percent			57	treatment policy; full analysis; R0005510:Results
40	A2 vs A1	md	0.0 percent		-0.4 to 0.5		treatment policy; full analysis; R0005510:Figure 1
40	A2 vs A4	md	-0.8 percent		-1.2 to -0.4		treatment policy; full analysis; R0005510:Figure 1
40	A3	change	-2.1 percent	1.5		56	not stated; full analysis; registry:outcomes
40	A3	change	-2.4 percent			38	hypothetical; full analysis; R0005510:Results
40	A3	change	-2.1 percent			56	treatment policy; full analysis; R0005510:Results
40	A3 vs A1	md	-0.3 percent		-0.7 to 0.2		treatment policy; full analysis; R0005510:Results
40	A3 vs A2	md	-0.3 percent		-0.7 to 0.1		treatment policy; full analysis; R0005510:Figure 1
40	A3 vs A4	md	-1.1 percent		-1.5 to -0.6		treatment policy; full analysis; R0005510:Figure 1
40	A3 vs A1	md	-0.5 percent		-1.0 to -0.1		hypothetical; full analysis; R0005510:Results
40	A3 vs A2	md	-0.3 percent		-0.7 to 0.2		hypothetical; full analysis; R0005510:Figure 1
40	A3 vs A4	md	-2.5 percent		-3.4 to -1.6		hypothetical; full analysis; R0005510:Figure 1
40	A4	change	-1.1 percent	1.3		54	not stated; full analysis; registry:outcomes
40	A4	change	-1.0 percent			54	treatment policy; full analysis; R0005510:Results
40	A4	change	0.1 percent			18	hypothetical; full analysis; R0005510:Results

Body weight change in kilograms (diabetes) (24 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	-8.3 kg			56	treatment policy; full analysis; R0005510:Figure 2
40	A1	change	-8.9 kg	8.5		56	not stated; full analysis; registry:outcomes
40	A1 vs A4	md	-6.2 kg		-9.7 to -2.6		hypothetical; full analysis; R0005510:Figure 2
40	A1	change	-9.6 kg			49	hypothetical; full analysis; R0005510:Figure 2
40	A1 vs A4	md	-5.7 kg		-8.4 to -3.1		treatment policy; full analysis; R0005510:Figure 2
40	A2 vs A1	md	-0.9 kg		-3.5 to 1.7		treatment policy; full analysis; R0005510:Figure 2
40	A2	change	-9.9 kg			38	hypothetical; full analysis; R0005510:Figure 2
40	A2 vs A1	md	-0.4 kg		-3.6 to 2.9		hypothetical; full analysis; R0005510:Figure 2
40	A2 vs A4	md	-6.5 kg		-10.2 to -2.8		hypothetical; full analysis; R0005510:Figure 2
40	A2	change	-10.1 kg	7.4		56	not stated; full analysis; registry:outcomes
40	A2	change	-9.3 kg			56	treatment policy; full analysis; R0005510:Figure 2
40	A2 vs A4	md	-6.7 kg		-9.3 to -4.0		treatment policy; full analysis; R0005510:Figure 2
40	A3	change	-13.1 kg	8.4		55	not stated; full analysis; registry:outcomes
40	A3 vs A2	md	-4.2 kg		-7.4 to -0.9		hypothetical; full analysis; R0005510:Figure 2
40	A3 vs A1	md	-4.5 kg		-7.6 to -1.4		hypothetical; full analysis; R0005510:Abstract
40	A3	change	-14.1 kg			44	hypothetical; full analysis; R0005510:Figure 2
40	A3	change	-11.7 kg			55	treatment policy; full analysis; R0005510:Figure 2
40	A3 vs A1	md	-3.4 kg		-6.0 to -0.8		treatment policy; full analysis; R0005510:Abstract
40	A3 vs A2	md	-2.5 kg		-5.1 to 0.1		treatment policy; full analysis; R0005510:Figure 2
40	A3 vs A4	md	-9.1 kg		-11.8 to -6.5		treatment policy; full analysis; R0005510:Figure 2
40	A3 vs A4	md	-10.7 kg		-14.2 to -7.1		hypothetical; full analysis; R0005510:Figure 2
40	A4	change	-3.4 kg			28	hypothetical; full analysis; R0005510:Figure 2
40	A4	change	-2.6 kg			53	treatment policy; full analysis; R0005510:Figure 2
40	A4	change	-2.3 kg	4.9		53	not stated; full analysis; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (4 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	1 / 60	not stated; safety; R0005510:Results
A2	events	0 / 60	not stated; safety; R0005510:Results
A3	events	0 / 62	not stated; safety; R0005510:Results
A4	events	1 / 59	not stated; safety; R0005510:Results

Percent body weight change (12 lines; O10)

Week	Arm	Statistic	Estimate	95% CI	Detail
40	A1	percent change	-7.3 percent		treatment policy; full analysis; R0005510:Results
40	A1	percent change	-8.3 percent		hypothetical; full analysis; R0005510:Results
40	A2	percent change	-9.0 percent		hypothetical; full analysis; R0005510:Results
40	A2	percent change	-8.3 percent		treatment policy; full analysis; R0005510:Results
40	A3 vs A2	md	-3.9 percent	-7.0 to -0.8	hypothetical; full analysis; R0005510:Results
40	A3	percent change	-12.9 percent		hypothetical; full analysis; R0005510:Results
40	A3 vs A1	md	-4.6 percent	-7.4 to -1.7	hypothetical; full analysis; R0005510:Results
40	A3	percent change	-10.8 percent		treatment policy; full analysis; R0005510:Results
40	A3 vs A1	md	-3.5 percent	-6.0 to -1.1	treatment policy; full analysis; R0005510:Results
40	A3 vs A2	md	-2.5 percent	-4.9 to 0	treatment policy; full analysis; R0005510:Results
40	A4	percent change	-2.8 percent		hypothetical; full analysis; R0005510:Results
40	A4	percent change	-2.0 percent		treatment policy; full analysis; R0005510:Results

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 60	not stated; safety; R0005510:Table 2
A2	events	0 / 60	not stated; safety; R0005510:Table 2
A3	events	0 / 62	not stated; safety; R0005510:Table 2
A4	events	1 / 59	not stated; safety; R0005510:Table 2

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 60	not stated; safety; R0005510:Table 2
A2	events	0 / 60	not stated; safety; R0005510:Table 2
A3	events	0 / 62	not stated; safety; R0005510:Table 2
A4	events	0 / 59	not stated; safety; R0005510:Table 2

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	4 / 60	not stated; safety; R0005510:Table 2
A2	events	2 / 60	not stated; safety; R0005510:Table 2
A3	events	1 / 62	not stated; safety; R0005510:Table 2
A4	events	2 / 59	not stated; safety; R0005510:Table 2

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	4 / 60	not stated; safety; R0005510:Table 2
A2	events	14 / 60	not stated; safety; R0005510:Table 2
A3	events	11 / 62	not stated; safety; R0005510:Table 2
A4	events	1 / 59	not stated; safety; R0005510:Table 2

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	13 / 60	not stated; safety; registry:adverse_events
A2	events	25 / 60	not stated; safety; registry:adverse_events
A3	events	23 / 62	not stated; safety; registry:adverse_events
A4	events	9 / 59	not stated; safety; registry:adverse_events

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	11 / 60	not stated; safety; registry:adverse_events
A2	events	14 / 60	not stated; safety; registry:adverse_events
A3	events	16 / 62	not stated; safety; registry:adverse_events
A4	events	4 / 59	not stated; safety; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	9 / 60	not stated; safety; registry:adverse_events
A2	events	20 / 60	not stated; safety; registry:adverse_events
A3	events	13 / 62	not stated; safety; registry:adverse_events
A4	events	7 / 59	not stated; safety; registry:adverse_events

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	2 / 60	not stated; safety; registry:adverse_events
A2	events	8 / 60	not stated; safety; registry:adverse_events
A3	events	12 / 62	not stated; safety; registry:adverse_events
A4	events	3 / 59	not stated; safety; registry:adverse_events

Discontinuation due to gastrointestinal adverse events (4 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	4 / 60	not stated; safety; R0005510:Supplement Table 5
A2	events	11 / 60	not stated; safety; R0005510:Supplement Table 5
A3	events	6 / 62	not stated; safety; R0005510:Supplement Table 5
A4	events	0 / 59	not stated; safety; R0005510:Supplement Table 5

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	2 / 60	not stated; safety; R0005510:Table 2
A2	events	1 / 60	not stated; safety; R0005510:Table 2
A3	events	3 / 62	not stated; safety; R0005510:Table 2
A4	events	0 / 59	not stated; safety; R0005510:Table 2

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 60	not stated; safety; R0005510:Table 2
A2	events	1 / 60	not stated; safety; R0005510:Table 2
A3	events	0 / 62	not stated; safety; R0005510:Table 2
A4	events	1 / 59	not stated; safety; R0005510:Table 2

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	0 / 60	not stated; safety; R0005510:Table 2
A2	events	0 / 60	not stated; safety; R0005510:Table 2
A3	events	1 / 62	not stated; safety; R0005510:Table 2
A4	events	0 / 59	not stated; safety; R0005510:Table 2