parallel randomized trial

STEP 2

Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity and Type 2 Diabetes

Type 2 diabetes (adults)NCT03552757S001740

Design

Randomized: 1,210
Start year: 2018
Treatment: 68 weeks, follow-up 75 weeks
Countries: multinational (149 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 or older; BMI 27 or more; HbA1c 7 to 10 percent; T2D on diet or up to 3 oral agents

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

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg	diet and exercise or up to 3 oral glucose lowering drugs; lifestyle: standard	403	403
A2	Semaglutide 2.4 mg subcutaneous once weekly Semaglutide 2.4 mg	diet and exercise or up to 3 oral glucose lowering drugs; lifestyle: standard	404	404
A3	Placebo Placebo	diet and exercise or up to 3 oral glucose lowering drugs; lifestyle: standard	403	403
A4	Pooled Semaglutide 1.0 and 2.4 mg pooled	lifestyle: standard

Baseline characteristics

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

Characteristic	Statistic	Semaglutide 1.0 mg subcutaneous once weekly A1	Semaglutide 2.4 mg subcutaneous once weekly A2	Placebo A3
age	mean (years)	56	55	55
age	sd (years)	10	11	11
asian	n	97	112	108
asian	percent	24.1	27.7	26.8
black	n	28	35	37
black	percent	6.9	8.7	9.2
bmi	mean (kg/m2)	35.3	35.9	35.9
bmi	sd (kg/m2)	5.9	6.4	6.5
diabetes duration	mean (years)	7.7	8.2	8.2
diabetes duration	sd (years)	5.9	6.2	6.2
egfr: 90 or more	n	265	270	259
egfr: 90 or more	percent	65.9	67.0	64.4
egfr: less than 90	n	137	133	143
egfr: less than 90	percent	34.1	33.0	35.6
egfr	mean (mL/min/1.73 m2)	95.4	96.3	94.6
egfr	sd (mL/min/1.73 m2)	18.1	18.5	19.3
established cvd	n	90	58	69
established cvd	percent	22.3	14.4	17.1
female	n	203	223	190
female	percent	50.4	55.2	47.1
hba1c	mean (percent)	8.1	8.1	8.1
hba1c	sd (percent)	0.8	0.8	0.8
hispanic	n	59	47	49
metformin use	n	372	364	353
other race american indian alaska native	n	0	4	2
other race american indian alaska native	percent		1.0	0.5
other race native hawaiian pacific islander	n	0	0	1
other race native hawaiian pacific islander	percent			0.2
other race other	n	6	16	13
other race other	percent	1.5	4.0	3.2
sbp	mean (mmHg)	130	130	130
sbp	sd (mmHg)	14	13	13
sglt2i use	n	90	95	99
sglt2i use	percent	22.3	23.5	24.6
uacr: 300 or more	n	17	13	11
uacr: 300 or more	percent	4.3	3.3	2.8
uacr: 30 to less than 300	n	72	64	71
uacr: 30 to less than 300	percent	18.2	16.2	17.8
uacr: less than 30	n	306	318	317
uacr: less than 30	percent	77.5	80.5	79.4
uacr	mean (mg/g)	13.7	12.5	13.2
weight	mean (kg)	99.0	99.9	100.5
weight	sd (kg)	21.1	22.5	20.9
white	n	272	237	242
white	percent	67.5	58.7	60.0

Results

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

HbA1c change (6 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
68	A1	change	-1.5 percent	1.1		376	treatment policy; full analysis; registry:outcomes
68	A2	change	-1.6 percent				treatment policy; full analysis; R0022984:Abstract
68	A2 vs A3	md	-1.5 percent		-1.7 to -1.4		hypothetical; full analysis; R0020858:Results
68	A2	change	-1.7 percent	1.2		381	treatment policy; full analysis; registry:outcomes
68	A3	change	-0.4 percent				treatment policy; full analysis; R0022984:Abstract
68	A3	change	-0.3 percent	1.3		374	treatment policy; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (3 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
68	A1	change	-7.1 kg	6.7	380	treatment policy; full analysis; registry:outcomes
68	A2	change	-9.9 kg	8.5	388	treatment policy; full analysis; registry:outcomes
68	A3	change	-3.4 kg	6.2	376	treatment policy; full analysis; registry:outcomes

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Events / N	Detail
68	A1	responders	272 / 376	treatment policy; full analysis; registry:outcomes
68	A2	responders	299 / 381	treatment policy; full analysis; registry:outcomes
68	A3	responders	99 / 374	treatment policy; full analysis; registry:outcomes

Level 2 or 3 hypoglycemia (episode rate) (2 lines; O04B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	rate				403	while on treatment; safety; registry:outcomes
	A3	rate				402	while on treatment; safety; registry:outcomes

Systolic blood pressure change (4 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
68	A1	change	-3 mmHg	15		379	treatment policy; full analysis; registry:outcomes
68	A2 vs A3	md	-4.8 mmHg		-6.7 to -2.9		hypothetical; full analysis; R0020858:Results
68	A2	change	-4 mmHg	14		387	treatment policy; full analysis; registry:outcomes
68	A3	change	0 mmHg	15		376	treatment policy; full analysis; registry:outcomes

Percent body weight change (15 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
68	A1	percent change	7.6 percent				hypothetical; full analysis; R0022984:Abstract
68	A1	percent change	-7.0 percent				treatment policy; full analysis; R0022984:Abstract
68	A1	percent change	-7.2 percent	6.6		380	treatment policy; full analysis; registry:outcomes
68	A2 vs A3	md	-7.6 percent		-8.6 to -6.6		hypothetical; full analysis; R0022984:Abstract
68	A2	percent change	-10.7 percent	7.8		404	while on treatment; full analysis; registry:outcomes
68	A2	percent change	-10.6 percent				hypothetical; full analysis; R0022984:Abstract
68	A2 vs A3	md	-6.2 percent		-7.3 to -5.2		treatment policy; full analysis; R0022984:Abstract
68	A2	percent change	-9.6 percent				treatment policy; full analysis; R0022984:Abstract
68	A2	percent change	-9.9 percent	8.0		404	treatment policy; full analysis; registry:outcomes
68	A2 vs A1	md	-2.7 percent		-3.7 to -1.6		treatment policy; full analysis; R0022984:Abstract
68	A2 vs A1	md	-3.1 percent		-4.1 to -2.1		hypothetical; full analysis; R0022984:Abstract
68	A3	percent change	-3.1 percent				hypothetical; full analysis; R0022984:Abstract
68	A3	percent change	-3.4 percent				treatment policy; full analysis; R0022984:Abstract
68	A3	percent change	-3.3 percent	5.5		403	treatment policy; full analysis; registry:outcomes
68	A3	percent change	-3.1 percent	5.2		403	while on treatment; full analysis; registry:outcomes

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
68	A1	responders			217 / 380	treatment policy; full analysis; registry:outcomes
68	A2	responders			257 / 404	while on treatment; full analysis; registry:outcomes
68	A2 vs A3	or	4.88	3.58 to 6.64		not stated; full analysis; registry:outcomes
68	A2	responders			267 / 404	treatment policy; full analysis; registry:outcomes
68	A2 vs A3	or	8.69	6.31 to 11.97		not stated; full analysis; registry:outcomes
68	A3	responders			94 / 403	while on treatment; full analysis; registry:outcomes
68	A3	responders			107 / 403	treatment policy; full analysis; registry:outcomes

Weight loss of 10 percent or more (3 lines; O11B)

Week	Arm	Statistic	Events / N	Detail
68	A1	responders	109 / 380	treatment policy; full analysis; registry:outcomes
68	A2	responders	177 / 388	treatment policy; full analysis; registry:outcomes
68	A3	responders	31 / 376	treatment policy; full analysis; registry:outcomes

Weight loss of 15 percent or more (3 lines; O11C)

Week	Arm	Statistic	Events / N	Detail
68	A1	responders	52 / 380	treatment policy; full analysis; registry:outcomes
68	A2	responders	100 / 388	treatment policy; full analysis; registry:outcomes
68	A3	responders	12 / 376	treatment policy; full analysis; registry:outcomes

Weight loss of 20 percent or more (3 lines; O11D)

Week	Arm	Statistic	Events / N	Detail
68	A1	responders	18 / 380	treatment policy; full analysis; registry:outcomes
68	A2	responders	51 / 388	treatment policy; full analysis; registry:outcomes
68	A3	responders	6 / 376	treatment policy; full analysis; registry:outcomes

Acute kidney injury (6 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	2 / 402	while on treatment; safety; R0020858:Table 2
A1	events	2 / 402	not stated; safety; registry:adverse_events
A2	events	3 / 403	while on treatment; safety; R0020858:Table 2
A2	events	2 / 403	not stated; safety; registry:adverse_events
A3	events	2 / 402	while on treatment; safety; R0020858:Table 2
A3	events	1 / 402	not stated; safety; registry:adverse_events

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	1 / 402	not stated; safety; registry:adverse_events
A2	events	1 / 403	not stated; safety; registry:adverse_events
A3	events	1 / 402	not stated; safety; registry:adverse_events

Hospitalization for heart failure (6 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	1 / 402	not stated; safety; cardiac failure congestive; registry:adverse_events
A1	events	0 / 402	not stated; safety; cardiac failure acute; registry:adverse_events
A2	events	0 / 403	not stated; safety; cardiac failure acute; registry:adverse_events
A2	events	1 / 403	not stated; safety; cardiac failure congestive; registry:adverse_events
A3	events	1 / 402	not stated; safety; cardiac failure acute; registry:adverse_events
A3	events	1 / 402	not stated; safety; cardiac failure congestive; registry:adverse_events

SF-36 physical component summary change (3 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
68	A1	change	1.9 points	6.4	370	treatment policy; full analysis; registry:outcomes
68	A2	change	2.3 points	7.2	376	treatment policy; full analysis; registry:outcomes
68	A3	change	0.9 points	6.6	365	treatment policy; full analysis; registry:outcomes

Physical functioning (any instrument) (6 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
68	A1	change	8.5 points	18.8	369	treatment policy; full analysis; registry:outcomes
68	A1	change	2.1 points	6.8	370	treatment policy; full analysis; registry:outcomes
68	A2	change	11.4 points	20.8	376	treatment policy; full analysis; registry:outcomes
68	A2	change	2.8 points	7.7	376	treatment policy; full analysis; registry:outcomes
68	A3	change	4.9 points	20.4	365	treatment policy; full analysis; registry:outcomes
68	A3	change	0.8 points	7.0	365	treatment policy; full analysis; registry:outcomes

Health related quality of life total score (any instrument) (3 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
68	A1	change	8.2 points	14.8	369	treatment policy; full analysis; registry:outcomes
68	A2	change	10.1 points	15.9	376	treatment policy; full analysis; registry:outcomes
68	A3	change	5.2 points	15.5	365	treatment policy; full analysis; registry:outcomes

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	31 / 402	not stated; safety; registry:adverse_events
A2	events	40 / 403	not stated; safety; registry:adverse_events
A3	events	37 / 402	not stated; safety; registry:adverse_events

Nausea (6 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	128 / 402	not stated; safety; registry:adverse_events
A1	events	2 / 402	not stated; safety; registry:adverse_events
A2	events	135 / 403	not stated; safety; registry:adverse_events
A2	events	1 / 403	not stated; safety; registry:adverse_events
A3	events	37 / 402	not stated; safety; registry:adverse_events
A3	events	0 / 402	not stated; safety; registry:adverse_events

Vomiting (6 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	54 / 402	not stated; safety; registry:adverse_events
A1	events	0 / 402	not stated; safety; registry:adverse_events
A2	events	86 / 403	not stated; safety; registry:adverse_events
A2	events	2 / 403	not stated; safety; registry:adverse_events
A3	events	11 / 402	not stated; safety; registry:adverse_events
A3	events	0 / 402	not stated; safety; registry:adverse_events

Diarrhea (6 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	88 / 402	not stated; safety; registry:adverse_events
A1	events	1 / 402	not stated; safety; registry:adverse_events
A2	events	86 / 403	not stated; safety; registry:adverse_events
A2	events	0 / 403	not stated; safety; registry:adverse_events
A3	events	48 / 402	not stated; safety; registry:adverse_events
A3	events	0 / 402	not stated; safety; registry:adverse_events

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	51 / 402	not stated; safety; registry:adverse_events
A2	events	70 / 403	not stated; safety; registry:adverse_events
A3	events	22 / 402	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (11 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 402	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	0 / 402	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	0 / 402	not stated; safety; cholecystitis chronic; registry:adverse_events
A2	events	1 / 403	not stated; safety; cholecystitis chronic; registry:adverse_events
A2	events	0 / 403	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	1 / 404	not stated; randomized; R0013578:Table 1
A2	events	1 / 403	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	0 / 402	not stated; safety; cholecystitis chronic; registry:adverse_events
A3	events	1 / 402	not stated; safety; cholecystitis acute; registry:adverse_events
A3	events	0 / 402	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	3 / 403	not stated; randomized; R0013578:Table 1

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 402	not stated; safety; obstructive pancreatitis; registry:adverse_events
A2	events	0 / 403	not stated; safety; obstructive pancreatitis; registry:adverse_events
A3	events	1 / 402	not stated; safety; obstructive pancreatitis; registry:adverse_events

Suicidal ideation or behavior (2 lines; O35A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A3	events				0 /	not stated; safety; R0040560:Figure 1
	A4	events				2 /	not stated; safety; R0040560:Figure 1

Intestinal obstruction or ileus (3 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 402	not stated; safety; small intestinal obstruction; registry:adverse_events
A2	events	1 / 403	not stated; safety; small intestinal obstruction; registry:adverse_events
A3	events	0 / 402	not stated; safety; small intestinal obstruction; registry:adverse_events