parallel randomized trial

STEP HFpEF DM

Effect of Semaglutide 2.4 mg Once-weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction, and Type 2 Diabetes

Type 2 diabetes (adults)Heart failure with left ventricular ejection fraction above 40 percent NCT04916470S000161

Design

Randomized: 616
Start year: 2021
Treatment: 52 weeks, follow-up 57 weeks
Countries: multinational (108 sites)
Sponsor: Novo Nordisk (industry)
Eligibility: age 18 or older; heart failure with LVEF 45% or more; BMI 30 or more; type 2 diabetes with HbA1c 10% or less

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 2.4 mg subcutaneous once weekly Semaglutide 2.4 mg	existing glucose lowering drugs except GLP-1 RA; standard heart failure care; lifestyle: standard	310	310	260
A2	Placebo Placebo	existing glucose lowering drugs except GLP-1 RA; standard heart failure care; lifestyle: standard	306	306	260

Baseline characteristics

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

Characteristic	Statistic	Semaglutide 2.4 mg subcutaneous once weekly A1	Placebo A2
age	median (years)	69.0	70.0
age	q1 (years)	62.0	63.0
age	q3 (years)	74.0	75.0
asian	n	45	31
asian	percent	14.5	10.1
black	n	13	5
black	percent	4.2	1.6
bmi: 30 to less than 35	n	108	112
bmi: 30 to less than 35	percent	34.8	36.6
bmi: 35 or more	n	202	194
bmi: 35 or more	percent	65.2	63.4
bmi	median (kg/m2)	36.9	36.9
bmi	q1 (kg/m2)	33.6	33.5
bmi	q3 (kg/m2)	41.5	41.1
diabetes duration	median (years)	8.0	8.0
diabetes duration	q1 (years)	3.6	4.1
diabetes duration	q3 (years)	14.3	15.2
egfr	median (mL/min/1.73 m2)	70.0	68.3
egfr	q1 (mL/min/1.73 m2)	52.0	49.0
egfr	q3 (mL/min/1.73 m2)	89.0	87.0
established cvd: coronary artery disease	n	79	69
established cvd: coronary artery disease	percent	25.5	22.5
female	n	128	145
female	percent	41.3	47.4
hba1c	median (percent)	6.7	6.9
hba1c	q1 (percent)	6.2	6.2
hba1c	q3 (percent)	7.4	7.7
hispanic	n	38	38
hispanic	percent	12.3	12.4
insulin use	n	53	75
insulin use	percent	17.1	24.5
lvef: 45 to less than 50	n	57	49
lvef: 45 to less than 50	percent	18.4	16.0
lvef: 50 to 59	n	121	138
lvef: 50 to 59	percent	39.0	45.1
lvef: 60 or more	n	132	119
lvef: 60 or more	percent	42.6	38.9
lvef	median (percent)	57.0	55.0
lvef	q1 (percent)	50.0	50.0
lvef	q3 (percent)	61.0	60.0
metformin use	n	235	208
metformin use	percent	75.8	68.0
other dpp4i use	n	55	37
other dpp4i use	percent	17.7	12.1
other race other	n	1	2
other race other	percent	0.3	0.7
other sulfonylurea use	n	57	51
other sulfonylurea use	percent	18.4	16.7
sbp	median (mmHg)	132.0	136.5
sbp	q1 (mmHg)	123.0	127.0
sbp	q3 (mmHg)	144.0	145.0
sglt2i use	n	107	95
sglt2i use	percent	34.5	31.0
waist	median (cm)	122.0	118.5
waist	q1 (cm)	113.0	111.0
waist	q3 (cm)	131.5	129.0
weight	median (kg)	103.8	101.7
weight	q1 (kg)	91.9	89.5
weight	q3 (kg)	119.0	116.4
white	n	251	268
white	percent	81.0	87.6

Analyses this trial contributes to

Results

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

HbA1c change (12 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	change	-0.7 percent	-0.9 to -0.6	124	treatment policy; full analysis; hba1c:6.5_to_less_than_7.5; R0018972:Table 2
52	A1	change	-0.7 percent	-0.9 to -0.4	112	treatment policy; full analysis; hba1c:less_than_6.5; R0018972:Table 2
52	A1 vs A2	md	-0.4 percent	-0.7 to -0.1		treatment policy; full analysis; hba1c:less_than_6.5; R0018972:Table 2
52	A1 vs A2	md	-0.8 percent	-1.0 to -0.6		treatment policy; full analysis; R0020223:Table 2
52	A1 vs A2	md	-0.9 percent	-1.2 to -0.7		treatment policy; full analysis; hba1c:6.5_to_less_than_7.5; R0018972:Table 2
52	A1	change	-0.7 percent		310	treatment policy; full analysis; R0020223:Table 2
52	A1	change	-0.7 percent	-1.1 to -0.4	74	treatment policy; full analysis; hba1c:7.5_or_more; R0018972:Table 2
52	A1 vs A2	md	-1.2 percent	-1.5 to -0.9		treatment policy; full analysis; hba1c:7.5_or_more; R0018972:Table 2
52	A2	change	-0.3 percent	-0.5 to 0.0	115	treatment policy; full analysis; hba1c:less_than_6.5; R0018972:Table 2
52	A2	change	0.1 percent		306	treatment policy; full analysis; R0020223:Table 2
52	A2	change	0.2 percent	0.0 to 0.4	102	treatment policy; full analysis; hba1c:6.5_to_less_than_7.5; R0018972:Table 2
52	A2	change	0.5 percent	0.2 to 0.8	89	treatment policy; full analysis; hba1c:7.5_or_more; R0018972:Table 2

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

Arm	Statistic	Events / N	Detail
A1	events	30 / 310	not stated; safety; R0018972:Table 4
A1	events	13 / 310	while on treatment; safety; R0020223:Supplement Table S10
A1	events	0 / 310	treatment policy; safety; R0020223:Supplement Table S9
A1	events	5 / 310	not stated; safety; R0018972:Table 4
A2	events	21 / 306	not stated; safety; R0018972:Table 4
A2	events	13 / 306	while on treatment; safety; R0020223:Supplement Table S10
A2	events	4 / 306	not stated; safety; R0018972:Table 4
A2	events	0 / 306	treatment policy; safety; R0020223:Supplement Table S9

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	rate					not stated; safety; R0018972:Table 4
	A2	rate					not stated; safety; R0018972:Table 4

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1 vs A2	md	-2.5 mmHg	-5.3 to 0.3		treatment policy; full analysis; R0020223:Table 2
52	A1	change	-4.2 mmHg		310	treatment policy; full analysis; R0020223:Table 2
52	A2	change	-1.7 mmHg		306	treatment policy; full analysis; R0020223:Table 2

Percent body weight change (6 lines; O10)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1 vs A2	md	-7.9 percent	-9.0 to -6.8		hypothetical; full analysis; R0020223:Supplement Table S8
52	A1	percent change	-11.0 percent		237	hypothetical; full analysis; R0020223:Supplement Table S8
52	A1	percent change	-9.8 percent		310	treatment policy; full analysis; R0020223:Table 2
52	A1 vs A2	md	-6.4 percent	-7.6 to -5.2		treatment policy; full analysis; R0020223:Table 2
52	A2	percent change	-3.4 percent		306	treatment policy; full analysis; R0020223:Table 2
52	A2	percent change	-3.1 percent		235	hypothetical; full analysis; R0020223:Supplement Table S8

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders	51.4		310	treatment policy; full analysis; R0020223:Table 2
52	A1 vs A2	or	7.3	4.7 to 11.4		treatment policy; full analysis; R0020223:Table 2
52	A2	responders	10.4		306	treatment policy; full analysis; R0020223:Table 2

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1 vs A2	or	5.4	2.8 to 10.2		treatment policy; full analysis; R0020223:Table 2
52	A1	responders	22.4		310	treatment policy; full analysis; R0020223:Table 2
52	A2	responders	4.0		306	treatment policy; full analysis; R0020223:Table 2

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders	7.3		310	treatment policy; full analysis; R0020223:Table 2
52	A1 vs A2	or	3.2	1.3 to 8.2		treatment policy; full analysis; R0020223:Table 2
52	A2	responders	1.8		306	treatment policy; full analysis; R0020223:Table 2

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	2 / 310	while on treatment; safety; R0020223:Supplement Table S10
A1	events	2 / 310	treatment policy; safety; R0020223:Supplement Table S9
A2	events	7 / 306	treatment policy; safety; R0020223:Supplement Table S9
A2	events	7 / 306	while on treatment; safety; R0020223:Supplement Table S10

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	6 / 310	treatment policy; safety; R0020223:Table 3
A1	events	4 / 310	while on treatment; safety; R0020223:Table 3
A2	events	10 / 306	treatment policy; safety; R0020223:Table 3
A2	events	10 / 306	while on treatment; safety; R0020223:Table 3

Hospitalization for heart failure (4 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	8 / 310	treatment policy; safety; heart failure; R0020223:Supplement Table S9
A1	events	4 / 310	while on treatment; safety; heart failure; R0020223:Table 3
A2	events	28 / 306	treatment policy; safety; heart failure; R0020223:Supplement Table S9
A2	events	27 / 306	while on treatment; safety; heart failure; R0020223:Table 3

Heart failure events (3 lines; O23B)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1 vs A2	hr	0.40	0.15 to 0.92		treatment policy; full analysis; R0020223:Table 2
A1	events			7 / 310	treatment policy; safety; R0020223:Table 3
A2	events			18 / 306	treatment policy; safety; R0020223:Table 3

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	change	13.5 points		310	treatment policy; full analysis; R0020223:Table 2
52	A1 vs A2	md	7.3 points	4.2 to 10.4		treatment policy; full analysis; R0020223:Table 2
52	A2	change	6.2 points		306	treatment policy; full analysis; R0020223:Table 2

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	60 / 310	treatment policy; safety; R0020223:Supplement Table S9
A1	events	55 / 310	while on treatment; safety; R0020223:Table 3
A2	events	90 / 306	treatment policy; safety; R0020223:Supplement Table S9
A2	events	88 / 306	while on treatment; safety; R0020223:Table 3

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	33 / 310	while on treatment; safety; R0020223:Table 3
A1	events	6 / 310	while on treatment; safety; R0020223:Table 3
A2	events	25 / 306	while on treatment; safety; R0020223:Table 3
A2	events	11 / 306	while on treatment; safety; R0020223:Table 3

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

Arm	Statistic	Events / N	Detail
A1	events	20 / 310	while on treatment; safety; R0020223:Table 3
A1	events	1 / 310	while on treatment; safety; R0020223:Table 3
A2	events	0 / 306	while on treatment; safety; R0020223:Table 3
A2	events	9 / 306	while on treatment; safety; R0020223:Table 3

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	3 / 310	treatment policy; safety; R0020223:Supplement Table S9
A1	events	1 / 310	while on treatment; safety; R0020223:Supplement Table S10
A2	events	2 / 306	treatment policy; safety; R0020223:Supplement Table S9
A2	events	2 / 306	while on treatment; safety; R0020223:Supplement Table S10

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	2 / 310	treatment policy; safety; R0020223:Supplement Table S9
A1	events	1 / 310	while on treatment; safety; R0020223:Supplement Table S10
A2	events	0 / 306	while on treatment; safety; R0020223:Supplement Table S10
A2	events	0 / 306	treatment policy; safety; R0020223:Supplement Table S9

Any cancer (4 lines; O39)

Arm	Statistic	Events / N	Detail
A1	events	7 / 310	while on treatment; safety; R0020223:Supplement Table S10
A1	events	7 / 310	treatment policy; safety; R0020223:Supplement Table S9
A2	events	8 / 306	treatment policy; safety; R0020223:Supplement Table S9
A2	events	7 / 306	while on treatment; safety; R0020223:Supplement Table S10

Cardiovascular death or heart failure events (3 lines; O40)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			9 / 310	treatment policy; randomized; R0019192:Figure 2
A1 vs A2	hr	0.46	0.20 to 0.98		treatment policy; randomized; R0019192:Figure 2
A2	events			20 / 306	treatment policy; randomized; R0019192:Figure 2

KCCQ clinical summary score change (6 lines; O41)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	change	16.6 points		234	hypothetical; full analysis; R0020223:Supplement Table S8
52	A1 vs A2	md	8.6 points	5.6 to 11.6		hypothetical; full analysis; R0020223:Supplement Table S8
52	A1	change	13.7 points		310	treatment policy; full analysis; R0020223:Table 2
52	A1 vs A2	md	7.3 points	4.1 to 10.4		treatment policy; full analysis; R0020223:Table 2
52	A2	change	7.9 points		232	hypothetical; full analysis; R0020223:Supplement Table S8
52	A2	change	6.4 points		306	treatment policy; full analysis; R0020223:Table 2