parallel randomized trial

PIONEER 5

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment

Type 2 diabetes (adults)Chronic kidney disease with diabetes NCT02827708S002025

Design

Randomized: 324
Start year: 2016
Treatment: 26 weeks, follow-up 31 weeks
Countries
Sponsor: Novo Nordisk A/S (industry)
Eligibility: type 2 diabetes; HbA1c 7.0 to 9.5 percent; moderate renal impairment

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: full analysis
Missing data: pattern mixture model; MMRM for trial product

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 14 mg oral once daily (original tablet) Oral semaglutide 14 mg	metformin or sulfonylurea or basal insulin with or without metformin; lifestyle: not reported	163	163
A2	Placebo Placebo	metformin or sulfonylurea or basal insulin with or without metformin; lifestyle: not reported	161	161

Baseline characteristics

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

Characteristic	Statistic	Semaglutide 14 mg oral once daily (original tablet) A1	Placebo A2	Whole trial ALL
age	mean (years)	71	70
age	sd (years)	8	8
asian	n	1	0
black	n	4	9
diabetes duration	mean (years)			14.0
diabetes duration	sd (years)			8.0
egfr: 15-<30	n			8
egfr: 15-<30	percent			2.5
egfr: 30-<60	n			285
egfr: 30-<60	percent			88.0
egfr: 60-<90	n			31
egfr: 60-<90	percent			9.6
egfr	mean (mL/min/1.73 m2)			47.6
egfr	sd (mL/min/1.73 m2)			9.7
female	n	80	88
hba1c	mean (percent)	8.0	7.9
hba1c	sd (percent)	0.7	0.7
hispanic	n	7	14
insulin use	n			115
metformin use	n			242
metformin use	percent			74.7
other background therapy: insulin with or without metformin	n			115
other background therapy: metformin	n			77
other background therapy: sulfonylurea with or without metformin	n			132
sbp	mean (mmHg)			137.5
sbp	sd (mmHg)			15.1
weight	mean (kg)			90.8
weight	sd (kg)			17.6
white	n	158	152

Analyses this trial contributes to

Results

58 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
26	A1 vs A2	md	-1.0 percent		-1.2 to -0.8		hypothetical; full analysis; registry:outcomes
26	A1	change	-1.2 percent	0.9		163	hypothetical; full analysis; registry:outcomes
26	A1	change	-1.1 percent	1.0		163	treatment policy; full analysis; registry:outcomes
26	A1 vs A2	md	-0.8 percent		-1.0 to -0.6		treatment policy; full analysis; registry:outcomes
26	A2	change	-0.1 percent	0.9		161	hypothetical; full analysis; registry:outcomes
26	A2	change	-0.2 percent	0.9		161	treatment policy; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (6 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A2	md	-2.7 kg		-3.5 to -1.9		hypothetical; full analysis; registry:outcomes
26	A1	change	-3.9 kg	3.6		163	hypothetical; full analysis; registry:outcomes
26	A1	change	-3.5 kg	3.8		163	treatment policy; full analysis; registry:outcomes
26	A1 vs A2	md	-2.5 kg		-3.2 to -1.8		treatment policy; full analysis; registry:outcomes
26	A2	change	-0.9 kg	2.9		161	treatment policy; full analysis; registry:outcomes
26	A2	change	-0.9 kg	2.9		161	hypothetical; full analysis; registry:outcomes

HbA1c below 7 percent (2 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	responders				89 / 154	not stated; full analysis; registry:outcomes
26	A2	responders				35 / 155	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				9 / 163	not stated; safety; registry:outcomes
	A2	events				3 / 161	not stated; safety; registry:outcomes

Systolic blood pressure change (2 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-8 mmHg	14		133	not stated; full analysis; registry:outcomes
26	A2	change	0 mmHg	13		141	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
26	A1	percent change	-3.75 percent	4.10		154	not stated; full analysis; registry:outcomes
26	A2	percent change	-0.92 percent	3.13		155	not stated; full analysis; registry:outcomes

Weight loss of 5 percent or more (2 lines; O11A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	responders				55 / 154	not stated; full analysis; registry:outcomes
26	A2	responders				15 / 155	not stated; full analysis; registry:outcomes

Weight loss of 10 percent or more (2 lines; O11B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	responders				13 / 154	not stated; full analysis; registry:outcomes
26	A2	responders				0 / 155	not stated; full analysis; registry:outcomes

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 163	not stated; safety; acute kidney injury; registry:adverse_events
	A2	events				1 / 161	not stated; safety; acute kidney injury; registry:adverse_events

All cause mortality (6 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	1 / 163	not stated; safety; registry:adverse_events
A1	events	1 / 15	not stated; full analysis; egfr:>=60; R0006400:Table 4
A1	events	0 / 148	not stated; full analysis; egfr:<60; R0006400:Table 4
A2	events	1 / 145	not stated; full analysis; egfr:<60; R0006400:Table 4
A2	events	2 / 161	not stated; safety; registry:adverse_events
A2	events	1 / 16	not stated; full analysis; egfr:>=60; R0006400:Table 4

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	1.78 points	7.16		163	not stated; full analysis; registry:outcomes
26	A2	change	-0.15 points	6.10		161	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
26	A1	change	0.71 points	7.21		163	not stated; full analysis; registry:outcomes
26	A2	change	-0.41 points	6.43		161	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				17 / 163	not stated; safety; registry:adverse_events
	A2	events				17 / 161	not stated; safety; registry:adverse_events

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				31 / 163	not stated; safety; registry:adverse_events
	A2	events				12 / 161	not stated; safety; registry:adverse_events

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				19 / 163	not stated; safety; registry:adverse_events
	A2	events				2 / 161	not stated; safety; registry:adverse_events

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				17 / 163	not stated; safety; registry:adverse_events
	A2	events				6 / 161	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				19 / 163	not stated; safety; registry:adverse_events
	A2	events				6 / 161	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (2 lines; O28)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 163	not stated; safety; biliary sepsis; registry:adverse_events
	A2	events				0 / 161	not stated; safety; biliary sepsis; registry:adverse_events

Any cancer (10 lines; O39)

Arm	Statistic	Events / N	Detail
A1	events	0 / 163	not stated; safety; bladder transitional cell carcinoma; registry:adverse_events
A1	events	0 / 163	not stated; safety; invasive ductal breast carcinoma; registry:adverse_events
A1	events	1 / 163	not stated; safety; lung neoplasm malignant; registry:adverse_events
A1	events	1 / 163	not stated; safety; malignant melanoma in situ; registry:adverse_events
A1	events	0 / 163	not stated; safety; renal cell carcinoma; registry:adverse_events
A2	events	1 / 161	not stated; safety; bladder transitional cell carcinoma; registry:adverse_events
A2	events	1 / 161	not stated; safety; invasive ductal breast carcinoma; registry:adverse_events
A2	events	0 / 161	not stated; safety; lung neoplasm malignant; registry:adverse_events
A2	events	0 / 161	not stated; safety; malignant melanoma in situ; registry:adverse_events
A2	events	1 / 161	not stated; safety; renal cell carcinoma; registry:adverse_events