parallel randomized trial

SUSTAIN 8

Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes

Type 2 diabetes (adults)NCT03136484S001847

Design

Randomized: 788
Start year: 2017
Treatment: 52 weeks, follow-up 57 weeks
Countries: USA, Canada, UK, Ireland, Sweden, Lebanon, Malaysia, Argentina, Mexico, Brazil, India (111 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin 1500 mg or maximum tolerated

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: hypothetical
Analysis population: full analysis
Missing data: multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg plus canagliflozin placebo	metformin 1500 mg or more or maximum tolerated; lifestyle: not reported	394	394
A2	Canagliflozin Canagliflozin 300 mg plus semaglutide placebo	metformin 1500 mg or more or maximum tolerated; lifestyle: not reported	394	394

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	Canagliflozin A2
age	mean (years)	55.7	57.5
age	sd (years)	11.1	10.7
asian	n	62	63
black	n	28	30
female	n	171	193
hba1c	mean (percent)	8.3	8.2
hba1c	sd (percent)	1.0	1.0
hispanic	n	156	137
other race american indian alaska native	n	1	3
other race native hawaiian pacific islander	n	0	0
other race not applicable	n	0	1
other race other	n	6	7
white	n	297	290

Analyses this trial contributes to

Results

52 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
52	A1	change	-1.7 percent	1.1		394	hypothetical; full analysis; registry:outcomes
52	A1 vs A2	md	-0.49 percent		-0.65 to -0.33		not stated; full analysis; registry:outcomes
52	A1 vs A2	md	-0.49 percent		-0.65 to -0.33		not stated; full analysis; registry:outcomes
52	A1	change	-1.5 percent	1.3		394	treatment policy; full analysis; registry:outcomes
52	A2	change	-1.0 percent	1.0		394	hypothetical; full analysis; registry:outcomes
52	A2	change	-1.0 percent	1.1		394	treatment policy; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (2 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-5.7 kg	5.4		394	not stated; full analysis; registry:outcomes
52	A2	change	-4.3 kg	4.0		394	not stated; full analysis; registry:outcomes

HbA1c below 7 percent (2 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	responders	76.1			293	not stated; full analysis; registry:outcomes
52	A2	responders	50.8			313	not stated; full analysis; registry:outcomes

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				6 / 392	not stated; safety; registry:outcomes
	A2	events				5 / 394	not stated; safety; registry:outcomes

Systolic blood pressure change (2 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-3.7 mmHg	14.0		394	not stated; full analysis; registry:outcomes
52	A2	change	-5.8 mmHg	13.5		394	not stated; full analysis; registry:outcomes

Percent body weight change (2 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	percent change	-6.2 percent	6.1		394	not stated; full analysis; registry:outcomes
52	A2	percent change	-4.7 percent	4.0		394	not stated; full analysis; registry:outcomes

Weight loss of 5 percent or more (4 lines; O11A)

Week	Arm	Statistic	Estimate	Events / N	Detail
52	A1	responders	51.1	394	hypothetical; full analysis; R0024549:Figure 5
52	A1	responders	52.7	298	not stated; full analysis; registry:outcomes
52	A2	responders	46.6	394	hypothetical; full analysis; R0024549:Figure 5
52	A2	responders	47.0	313	not stated; full analysis; registry:outcomes

Weight loss of 10 percent or more (4 lines; O11B)

Week	Arm	Statistic	Estimate	Events / N	Detail
52	A1	responders	22.3	394	hypothetical; full analysis; R0024549:Figure 5
52	A1	responders	23.2	298	not stated; full analysis; registry:outcomes
52	A2	responders	8.9	313	not stated; full analysis; registry:outcomes
52	A2	responders	8.9	394	hypothetical; full analysis; R0024549:Figure 5

Weight loss of 15 percent or more (2 lines; O11C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	responders	6.8			394	hypothetical; full analysis; R0024549:Figure 5
52	A2	responders	0.9			394	hypothetical; full analysis; R0024549:Figure 5

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 392	not stated; safety; registry:adverse_events
	A2	events				0 / 394	not stated; safety; registry:adverse_events

SF-36 physical component summary change (2 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	2.7 points	6.7		394	not stated; full analysis; registry:outcomes
52	A2	change	2.9 points	6.2		394	not stated; full analysis; registry:outcomes

Physical functioning (any instrument) (2 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	1.9 points	7.1		394	not stated; full analysis; registry:outcomes
52	A2	change	2.7 points	6.7		394	not stated; full analysis; registry:outcomes

Health related quality of life total score (any instrument) (2 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	5.8 points	7.0		394	not stated; full analysis; registry:outcomes
52	A2	change	4.8 points	7.2		394	not stated; full analysis; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				18 / 392	not stated; safety; registry:adverse_events
	A2	events				21 / 394	not stated; safety; registry:adverse_events

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				89 / 392	not stated; safety; registry:adverse_events
	A2	events				26 / 394	not stated; safety; registry:adverse_events

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				50 / 392	not stated; safety; registry:adverse_events
	A2	events				9 / 394	not stated; safety; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	59 / 392	not stated; safety; registry:adverse_events
A1	events	1 / 392	not stated; safety; registry:adverse_events
A2	events	37 / 394	not stated; safety; registry:adverse_events
A2	events	0 / 394	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				20 / 392	not stated; safety; registry:adverse_events
	A2	events				23 / 394	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 392	not stated; safety; Cholecystitis chronic; registry:adverse_events
A1	events	0 / 392	not stated; safety; Cholelithiasis; registry:adverse_events
A2	events	3 / 394	not stated; safety; Cholelithiasis; registry:adverse_events
A2	events	1 / 394	not stated; safety; Cholecystitis chronic; registry:adverse_events

Intestinal obstruction or ileus (2 lines; O37B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 392	not stated; safety; Small intestinal obstruction; registry:adverse_events
	A2	events				1 / 394	not stated; safety; Small intestinal obstruction; registry:adverse_events