parallel randomized trial

PIONEER 11

China Multi-regional Clinical Trial: Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only

Type 2 diabetes (adults)NCT04109547S001791

Design

Randomized: 521
Start year: 2019
Treatment: 26 weeks, follow-up 31 weeks
Countries: China, Taiwan, Hungary, Serbia, Ukraine (52 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 or older; HbA1c 7.0 to 10.0 percent at screening, 7.0 to 9.5 at randomization; no glucose lowering drugs; eGFR 60 or more

Conduct and analysis

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

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 3 mg oral once daily (original tablet) Oral semaglutide 3 mg	diet and exercise; lifestyle: not reported	130	130	121
A2	Semaglutide 7 mg oral once daily (original tablet) Oral semaglutide 7 mg	diet and exercise; lifestyle: not reported	130	130	122
A3	Semaglutide 14 mg oral once daily (original tablet) Oral semaglutide 14 mg	diet and exercise; lifestyle: not reported	130	130	118
A4	Placebo Placebo	diet and exercise; lifestyle: not reported	131	131	121

Baseline characteristics

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

Characteristic	Statistic	Semaglutide 3 mg oral once daily (original tablet) A1	Semaglutide 7 mg oral once daily (original tablet) A2	Semaglutide 14 mg oral once daily (original tablet) A3	Placebo A4
age	mean (years)	54	52	53	51
age	sd (years)	11	11	10	11
asian	n	97	98	97	98
asian	percent	74.6	75.4	74.6	74.8
bmi	mean (kg/m2)	27.8	28.4	28.2	28.4
bmi	sd (kg/m2)	4.8	5.1	5.8	5.0
diabetes duration	mean (years)	2.3	1.7	2.1	2.7
diabetes duration	sd (years)	3.0	2.4	3.3	3.8
egfr	mean (mL/min/1.73 m2)	102	102	102	104
egfr	sd (mL/min/1.73 m2)	14	14	14	15
female	n	58	41	47	43
female	percent	44.6	31.5	36.2	32.8
hba1c	mean (percent)	7.9	7.9	8.0	8.0
hba1c	sd (percent)	0.6	0.7	0.9	0.7
sbp	mean (mmHg)	127	127	127	129
sbp	sd (mmHg)	15	14	14	14
waist	mean (cm)	95.8	98.0	96.9	97.5
waist	sd (cm)	11.5	11.9	13.6	11.9
weight	mean (kg)	76.6	80.8	79.7	81.1
weight	sd (kg)	15.8	17.4	19.7	16.5
white	n	33	32	33	33
white	percent	25.4	24.6	25.4	25.2

Analyses this trial contributes to

Results

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

HbA1c change (16 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.1 percent	0.7		114	hypothetical; full analysis; registry:outcomes
26	A1 vs A4	md	-8 mmol/mol		-11 to -6		treatment policy; full analysis; R0019663:Figure 2
26	A1 vs A4	md	-13 mmol/mol		-15 to -10		hypothetical; full analysis; region:china; R0019663:Figure 3
26	A1 vs A4	md	-9 mmol/mol		-12 to -7		treatment policy; full analysis; region:china; R0019663:Figure 3
26	A1 vs A4	md	-1.0 percent		-1.2 to -0.8		hypothetical; full analysis; R0019663:Results
26	A2	change	-1.5 percent	0.8		117	hypothetical; full analysis; registry:outcomes
26	A2 vs A4	md	-18 mmol/mol		-20 to -16		hypothetical; full analysis; region:china; R0019663:Figure 3
26	A2 vs A4	md	-15 mmol/mol		-17 to -12		treatment policy; full analysis; region:china; R0019663:Figure 3
26	A2 vs A4	md	-13 mmol/mol		-15 to -10		treatment policy; full analysis; R0019663:Figure 2
26	A2 vs A4	md	-1.4 percent		-1.6 to -1.2		hypothetical; full analysis; R0019663:Results
26	A3 vs A4	md	-1.5 percent		-1.8 to -1.3		hypothetical; full analysis; R0019663:Results
26	A3 vs A4	md	-14 mmol/mol		-16 to -11		treatment policy; full analysis; R0019663:Figure 2
26	A3 vs A4	md	-18 mmol/mol		-20 to -16		hypothetical; full analysis; region:china; R0019663:Figure 3
26	A3 vs A4	md	-14 mmol/mol		-17 to -12		treatment policy; full analysis; region:china; R0019663:Figure 3
26	A3	change	-1.6 percent	1.0		116	hypothetical; full analysis; registry:outcomes
26	A4	change	-0.2 percent	0.9		106	hypothetical; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (16 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.1 kg	3.3		115	hypothetical; full analysis; registry:outcomes
26	A1 vs A4	md	-0.2 kg		-1.1 to 0.7		treatment policy; full analysis; region:china; R0019663:Figure 5
26	A1 vs A4	md	-0.1 kg		-1.0 to 0.8		hypothetical; full analysis; region:china; R0019663:Figure 5
26	A1 vs A4	md	-0.0 kg		-0.9 to 0.8		hypothetical; full analysis; R0019663:Results
26	A1 vs A4	md	-0.1 kg		-0.9 to 0.7		treatment policy; full analysis; R0019663:Figure 4
26	A2 vs A4	md	-1.1 kg		-2.0 to -0.3		treatment policy; full analysis; R0019663:Figure 4
26	A2	change	-2.2 kg	3.4		119	hypothetical; full analysis; registry:outcomes
26	A2 vs A4	md	-1.2 kg		-2.1 to -0.3		treatment policy; full analysis; region:china; R0019663:Figure 5
26	A2 vs A4	md	-1.2 kg		-2.0 to -0.4		hypothetical; full analysis; R0019663:Results
26	A2 vs A4	md	-1.2 kg		-2.1 to -0.4		hypothetical; full analysis; region:china; R0019663:Figure 5
26	A3 vs A4	md	-1.9 kg		-2.8 to -1.1		treatment policy; full analysis; R0019663:Figure 4
26	A3	change	-3.1 kg	3.7		116	hypothetical; full analysis; registry:outcomes
26	A3 vs A4	md	-2.0 kg		-2.8 to -1.2		hypothetical; full analysis; R0019663:Results
26	A3 vs A4	md	-1.9 kg		-2.8 to -1.0		hypothetical; full analysis; region:china; R0019663:Figure 5
26	A3 vs A4	md	-1.8 kg		-2.8 to -0.8		treatment policy; full analysis; region:china; R0019663:Figure 5
26	A4	change	-1.1 kg	2.7		106	hypothetical; full analysis; registry:outcomes

HbA1c below 7 percent (14 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	responders			75 / 114	hypothetical; full analysis; R0019663:Table 2
26	A1 vs A4	or	5.79	3.16 to 10.59		treatment policy; full analysis; R0019663:Table 2
26	A1	responders			79 / 124	treatment policy; full analysis; R0019663:Table 2
26	A1 vs A4	or	7.08	3.83 to 13.11		hypothetical; full analysis; R0019663:Table 2
26	A2	responders			102 / 126	treatment policy; full analysis; R0019663:Table 2
26	A2	responders			100 / 117	hypothetical; full analysis; R0019663:Table 2
26	A2 vs A4	or	22.26	11.03 to 44.94		hypothetical; full analysis; R0019663:Table 2
26	A2 vs A4	or	14.58	7.58 to 28.04		treatment policy; full analysis; R0019663:Table 2
26	A3 vs A4	or	22.04	10.94 to 44.37		hypothetical; full analysis; R0019663:Table 2
26	A3	responders			95 / 123	treatment policy; full analysis; R0019663:Table 2
26	A3 vs A4	or	13.10	6.91 to 24.83		treatment policy; full analysis; R0019663:Table 2
26	A3	responders			92 / 116	hypothetical; full analysis; R0019663:Table 2
26	A4	responders			29 / 124	treatment policy; full analysis; R0019663:Table 2
26	A4	responders			27 / 106	hypothetical; full analysis; R0019663:Table 2

Level 2 or 3 hypoglycemia (participants) (12 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	while on treatment; safety; registry:outcomes
A1	events	0 / 130	while on treatment; safety; R0019663:Table 3
A1	events	1 / 130	while on treatment; safety; R0019663:Table 3
A2	events	0 / 130	while on treatment; safety; registry:outcomes
A2	events	1 / 130	while on treatment; safety; R0019663:Table 3
A2	events	0 / 130	while on treatment; safety; R0019663:Table 3
A3	events	0 / 129	while on treatment; safety; R0019663:Table 3
A3	events	0 / 129	while on treatment; safety; R0019663:Table 3
A3	events	0 / 129	while on treatment; safety; registry:outcomes
A4	events	0 / 131	while on treatment; safety; R0019663:Table 3
A4	events	0 / 131	while on treatment; safety; registry:outcomes
A4	events	0 / 131	while on treatment; safety; R0019663:Table 3

Systolic blood pressure change (7 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	1 mmHg	13		121	while on treatment; safety; registry:outcomes
26	A1 vs A4	md	2 mmHg		-1 to 5		not stated; safety; R0019663:Supplement Table 7
26	A2	change	-2 mmHg	12		122	while on treatment; safety; registry:outcomes
26	A2 vs A4	md	-0 mmHg		-3 to 3		not stated; safety; R0019663:Supplement Table 7
26	A3 vs A4	md	-3 mmHg		-6 to 0		not stated; safety; R0019663:Supplement Table 7
26	A3	change	-4 mmHg	13		116	while on treatment; safety; registry:outcomes
26	A4	change	-2 mmHg	13		121	while on treatment; safety; registry:outcomes

Percent body weight change (14 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	percent change	-1 percent	4		124	treatment policy; full analysis; R0019663:Table 2
26	A1	percent change	-1 percent	4		115	hypothetical; full analysis; R0019663:Table 2
26	A1 vs A4	md	-0.1 percent		-1.2 to 0.9		hypothetical; full analysis; R0019663:Table 2
26	A1 vs A4	md	-0.2 percent		-1.3 to 0.8		treatment policy; full analysis; R0019663:Table 2
26	A2	percent change	-3 percent	4		119	hypothetical; full analysis; R0019663:Table 2
26	A2 vs A4	md	-1.6 percent		-2.7 to -0.6		treatment policy; full analysis; R0019663:Table 2
26	A2	percent change	-3 percent	4		127	treatment policy; full analysis; R0019663:Table 2
26	A2 vs A4	md	-1.7 percent		-2.7 to -0.6		hypothetical; full analysis; R0019663:Table 2
26	A3	percent change	-4 percent	5		123	treatment policy; full analysis; R0019663:Table 2
26	A3	percent change	-4 percent	5		116	hypothetical; full analysis; R0019663:Table 2
26	A3 vs A4	md	-2.7 percent		-3.7 to -1.6		hypothetical; full analysis; R0019663:Table 2
26	A3 vs A4	md	-2.6 percent		-3.7 to -1.4		treatment policy; full analysis; R0019663:Table 2
26	A4	percent change	-1 percent	3		106	hypothetical; full analysis; R0019663:Table 2
26	A4	percent change	-1 percent	3		124	treatment policy; full analysis; R0019663:Table 2

Weight loss of 5 percent or more (14 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	responders			17 / 115	hypothetical; full analysis; R0019663:Table 2
26	A1 vs A4	or	1.43	0.65 to 3.18		hypothetical; full analysis; R0019663:Table 2
26	A1	responders			18 / 124	treatment policy; full analysis; R0019663:Table 2
26	A1 vs A4	or	1.69	0.75 to 3.77		treatment policy; full analysis; R0019663:Table 2
26	A2 vs A4	or	3.26	1.54 to 6.92		treatment policy; full analysis; R0019663:Table 2
26	A2	responders			29 / 119	hypothetical; full analysis; R0019663:Table 2
26	A2 vs A4	or	2.91	1.39 to 6.08		hypothetical; full analysis; R0019663:Table 2
26	A2	responders			30 / 127	treatment policy; full analysis; R0019663:Table 2
26	A3 vs A4	or	5.28	2.58 to 10.80		hypothetical; full analysis; R0019663:Table 2
26	A3	responders			43 / 116	hypothetical; full analysis; R0019663:Table 2
26	A3	responders			44 / 123	treatment policy; full analysis; R0019663:Table 2
26	A3 vs A4	or	5.55	2.67 to 11.53		treatment policy; full analysis; R0019663:Table 2
26	A4	responders			11 / 106	hypothetical; full analysis; R0019663:Table 2
26	A4	responders			11 / 124	treatment policy; full analysis; R0019663:Table 2

Weight loss of 10 percent or more (14 lines; O11B)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	responders			6 / 124	treatment policy; full analysis; R0019663:Table 2
26	A1	responders			5 / 115	hypothetical; full analysis; R0019663:Table 2
26	A1 vs A4	or	8.29	0.49 to 139.1		hypothetical; full analysis; R0019663:Table 2
26	A1 vs A4	or	11.94	0.69 to 206.0		treatment policy; full analysis; R0019663:Table 2
26	A2	responders			7 / 119	hypothetical; full analysis; R0019663:Table 2
26	A2	responders			7 / 127	treatment policy; full analysis; R0019663:Table 2
26	A2 vs A4	or	15.65	0.92 to 265.3		treatment policy; full analysis; R0019663:Table 2
26	A2 vs A4	or	13.15	0.81 to 214.1		hypothetical; full analysis; R0019663:Table 2
26	A3 vs A4	or	22.59	1.44 to 355.7		hypothetical; full analysis; R0019663:Table 2
26	A3	responders			12 / 116	hypothetical; full analysis; R0019663:Table 2
26	A3	responders			12 / 123	treatment policy; full analysis; R0019663:Table 2
26	A3 vs A4	or	25.26	1.54 to 414.7		treatment policy; full analysis; R0019663:Table 2
26	A4	responders			0 / 124	treatment policy; full analysis; R0019663:Table 2
26	A4	responders			0 / 106	hypothetical; full analysis; R0019663:Table 2

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	while on treatment; safety; R0019663:Supplement Table 6
A2	events	1 / 130	while on treatment; safety; R0019663:Supplement Table 6
A3	events	0 / 129	while on treatment; safety; R0019663:Supplement Table 6
A4	events	0 / 131	while on treatment; safety; R0019663:Supplement Table 6

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	while on treatment; safety; R0019663:Table 3
A2	events	0 / 130	while on treatment; safety; R0019663:Table 3
A3	events	0 / 129	while on treatment; safety; R0019663:Table 3
A4	events	0 / 131	while on treatment; safety; R0019663:Table 3

Three point MACE (4 lines; O21)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	while on treatment; safety; R0019663:Supplement Table 6
A2	events	0 / 130	while on treatment; safety; R0019663:Supplement Table 6
A3	events	0 / 129	while on treatment; safety; R0019663:Supplement Table 6
A4	events	0 / 131	while on treatment; safety; R0019663:Supplement Table 6

Hospitalization for heart failure (4 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	while on treatment; safety; R0019663:Supplement Table 6
A2	events	0 / 130	while on treatment; safety; R0019663:Supplement Table 6
A3	events	0 / 129	while on treatment; safety; R0019663:Supplement Table 6
A4	events	0 / 131	while on treatment; safety; R0019663:Supplement Table 6

SF-36 physical component summary change (4 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	0.66 points	5.21	115	hypothetical; full analysis; registry:outcomes
26	A2	change	0.88 points	4.98	119	hypothetical; full analysis; registry:outcomes
26	A3	change	0.39 points	4.60	115	hypothetical; full analysis; registry:outcomes
26	A4	change	0.94 points	4.71	106	hypothetical; full analysis; registry:outcomes

Physical functioning (any instrument) (4 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	0.25 points	4.83	115	hypothetical; full analysis; registry:outcomes
26	A2	change	0.97 points	5.16	119	hypothetical; full analysis; registry:outcomes
26	A3	change	0.34 points	4.24	115	hypothetical; full analysis; registry:outcomes
26	A4	change	0.87 points	4.98	106	hypothetical; full analysis; registry:outcomes

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	6 / 130	while on treatment; safety; R0019663:Table 3
A2	events	10 / 130	while on treatment; safety; R0019663:Table 3
A3	events	5 / 129	while on treatment; safety; R0019663:Table 3
A4	events	2 / 131	while on treatment; safety; R0019663:Table 3

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	3 / 130	while on treatment; safety; R0019663:Table 3
A2	events	2 / 130	while on treatment; safety; R0019663:Table 3
A3	events	3 / 129	while on treatment; safety; R0019663:Table 3
A4	events	3 / 131	while on treatment; safety; R0019663:Table 3

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	6 / 130	while on treatment; safety; R0019663:Table 3
A2	events	4 / 130	while on treatment; safety; R0019663:Table 3
A3	events	8 / 129	while on treatment; safety; R0019663:Table 3
A4	events	2 / 131	while on treatment; safety; R0019663:Table 3

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	4 / 130	while on treatment; safety; R0019663:Table 3
A2	events	12 / 130	while on treatment; safety; R0019663:Table 3
A3	events	12 / 129	while on treatment; safety; R0019663:Table 3
A4	events	2 / 131	while on treatment; safety; R0019663:Table 3

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	1 / 130	while on treatment; safety; R0019663:Table 3
A2	events	7 / 130	while on treatment; safety; R0019663:Table 3
A3	events	3 / 129	while on treatment; safety; R0019663:Table 3
A4	events	0 / 131	while on treatment; safety; R0019663:Table 3

Gallbladder and biliary disease (8 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	not stated; safety; Cholelithiasis; registry:adverse_events
A1	events	0 / 130	not stated; safety; Cholecystitis acute; registry:adverse_events
A2	events	1 / 130	not stated; safety; Cholecystitis acute; registry:adverse_events
A2	events	2 / 130	not stated; safety; Cholelithiasis; registry:adverse_events
A3	events	0 / 129	not stated; safety; Cholecystitis acute; registry:adverse_events
A3	events	1 / 129	not stated; safety; Cholelithiasis; registry:adverse_events
A4	events	0 / 131	not stated; safety; Cholecystitis acute; registry:adverse_events
A4	events	0 / 131	not stated; safety; Cholelithiasis; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	while on treatment; safety; R0019663:Supplement Table 6
A2	events	0 / 130	while on treatment; safety; R0019663:Supplement Table 6
A3	events	0 / 129	while on treatment; safety; R0019663:Supplement Table 6
A4	events	0 / 131	while on treatment; safety; R0019663:Supplement Table 6

Medullary thyroid carcinoma (3 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	while on treatment; safety; R0019663:Supplement Table 6
A3	events	0 / 129	while on treatment; safety; R0019663:Supplement Table 6
A4	events	0 / 131	while on treatment; safety; R0019663:Supplement Table 6

Thyroid cancer (any) (4 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	while on treatment; safety; R0019663:Supplement Table 6
A2	events	1 / 130	while on treatment; safety; R0019663:Supplement Table 6
A3	events	0 / 129	while on treatment; safety; R0019663:Supplement Table 6
A4	events	0 / 131	while on treatment; safety; R0019663:Supplement Table 6

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	6 / 130	while on treatment; safety; diabetic retinopathy; R0019663:Results
A2	events	0 / 130	while on treatment; safety; diabetic retinopathy; R0019663:Results
A3	events	0 / 129	while on treatment; safety; diabetic retinopathy; R0019663:Results
A4	events	2 / 131	while on treatment; safety; diabetic retinopathy; R0019663:Results

Death by suicide (4 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 130	while on treatment; safety; R0019663:Table 3
A2	events	0 / 130	while on treatment; safety; R0019663:Table 3
A3	events	0 / 129	while on treatment; safety; R0019663:Table 3
A4	events	0 / 131	while on treatment; safety; R0019663:Table 3