parallel randomized trial

NCT02964247

LIRA-ADD2SGLT2i - Liraglutide Versus Placebo as add-on to SGLT2 Inhibitors

Type 2 diabetes (adults)NCT02964247S000022

Design

Randomized: 303
Start year: 2017
Treatment: 26 weeks, follow-up 27 weeks
Countries: Brazil, India, Israel, Mexico, Russian Federation, United Arab Emirates, United States (74 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 or more; HbA1c 7.0 to 9.5%; BMI 20 or more; stable SGLT2i at least 90 days with or without metformin; eGFR 60 or more

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: pattern mixture model multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg	SGLT2i with or without metformin; lifestyle: not reported	203	203	187
A2	Placebo Placebo	SGLT2i with or without metformin; lifestyle: not reported	100	100	93

Baseline characteristics

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

Characteristic	Statistic	Liraglutide 1.8 mg subcutaneous once daily A1	Placebo A2
age	mean (years)	54.7	56.0
age	sd (years)	10.1	9.9
asian	n	38	15
asian	percent	18.7	15.0
black	n	12	5
black	percent	5.9	5.0
bmi: 25 to less than 30	n	72	22
bmi: 25 to less than 30	percent	35.5	22.0
bmi: 30 to less than 35	n	64	34
bmi: 30 to less than 35	percent	31.5	34.0
bmi: 35 to less than 40	n	34	20
bmi: 35 to less than 40	percent	16.7	20.0
bmi: 40 or more	n	20	10
bmi: 40 or more	percent	9.9	10.0
bmi: less than 25	n	13	14
bmi: less than 25	percent	6.4	14.0
bmi	mean (kg/m2)	32.0	32.6
bmi	sd (kg/m2)	6.0	6.5
diabetes duration	mean (years)	10.1	9.6
diabetes duration	sd (years)	7.2	6.7
egfr: 60 to less than 90	n	53	28
egfr: 60 to less than 90	percent	26.1	28.0
egfr: 90 or more	n	149	72
egfr: 90 or more	percent	73.4	72.0
female	n	78	42
hba1c: 8.5 or more	n	51	21
hba1c: 8.5 or more	percent	25.1	21.0
hba1c: less than 8.5	n	152	79
hba1c: less than 8.5	percent	74.9	79.0
hba1c	mean (percent)	8.0	8.0
hba1c	sd (percent)	0.7	0.6
hispanic	n	59	35
metformin use	n	191	95
metformin use	percent	94.1	95.0
other race american indian alaska native	n	0	1
other race native hawaiian pacific islander	n	1	0
other race other	n	22	21
other race other	percent	10.8	21.0
sbp	mean (mmHg)	127.5	128.5
sbp	sd (mmHg)	12.7	14.4
sglt2i use	n	203	100
sglt2i use	percent	100.0	100.0
uacr: more than 30	n	51	18
uacr: more than 30	percent	25.9	18.6
weight	mean (kg)	91.0	91.4
weight	sd (kg)	21.0	21.4
white	n	131	59
white	percent	64.5	59.0

Results

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

HbA1c change (44 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A2	md	-0.67 percent		-0.87 to -0.47		treatment policy; full analysis; R0024267:Supplement Figure S2
26	A1	change	-1.07 percent			66	hypothetical; other; diabetes_duration:less_than_5.6; R0024029:Table 1
26	A1 vs A2	md	-0.57 percent		-0.94 to -0.20		hypothetical; other; diabetes_duration:less_than_5.6; R0024029:Table 1
26	A1 vs A2	md	-0.74 percent		-0.94 to -0.53		hypothetical; full analysis; R0024267:Supplement Table S3
26	A1	change	-1.11 percent			65	hypothetical; other; hba1c:7.0_to_less_than_7.6; R0024029:Table 1
26	A1 vs A2	md	-0.20 percent		-0.59 to 0.19		hypothetical; other; hba1c:7.0_to_less_than_7.6; R0024029:Table 1
26	A1	change	-1.05 percent	0.85		203	hypothetical; full analysis; registry:outcomes
26	A1	change	-0.99 percent			63	hypothetical; other; hba1c:7.6_to_8.1; R0024029:Table 1
26	A1 vs A2	md	-0.68 percent		-1.03 to -0.33		hypothetical; other; hba1c:7.6_to_8.1; R0024029:Table 1
26	A1 vs A2	md	-0.70 percent		-0.89 to -0.50		treatment policy; full analysis; R0024267:Supplement Figure S2
26	A1 vs A2	md	-0.98 percent		-1.33 to -0.64		hypothetical; other; hba1c:8.2_to_9.5; R0024029:Table 1
26	A1	change	-1.01 percent			75	hypothetical; other; hba1c:8.2_to_9.5; R0024029:Table 1
26	A1	change	-1.02 percent			203	hypothetical; full analysis; R0024267:Supplement Table S3
26	A1 vs A2	md	-0.65 percent		-0.85 to -0.45		treatment policy; full analysis; R0024267:Supplement Figure S2
26	A1 vs A2	md	-0.68 percent		-0.89 to -0.47		treatment policy; full analysis; R0024267:Supplement Figure S2
26	A1	change	-0.98 percent			202	treatment policy; full analysis; R0024267:Results
26	A1	change	-1.00 percent	0.86		203	treatment policy; full analysis; registry:outcomes
26	A1	change	-0.91 percent			61	hypothetical; other; bmi:28.6_to_33.9; R0024029:Table 1
26	A1 vs A2	md	-0.44 percent		-0.78 to -0.09		hypothetical; other; bmi:28.6_to_33.9; R0024029:Table 1
26	A1 vs A2	md	-0.61 percent		-0.83 to -0.40		hypothetical; full analysis; R0024267:Supplement Figure S2
26	A1	change	-1.10 percent			67	hypothetical; other; bmi:34.0_or_more; R0024029:Table 1
26	A1 vs A2	md	-0.70 percent		-1.07 to -0.33		hypothetical; other; bmi:34.0_or_more; R0024029:Table 1
26	A1 vs A2	md	-0.68 percent		-0.89 to -0.48		treatment policy; full analysis; R0024267:Results
26	A1	change	-1.08 percent			75	hypothetical; other; bmi:less_than_28.6; R0024029:Table 1
26	A1 vs A2	md	-0.97 percent		-1.36 to -0.59		hypothetical; other; bmi:less_than_28.6; R0024029:Table 1
26	A1 vs A2	md	-0.60 percent		-0.80 to -0.39		hypothetical; full analysis; R0024267:Supplement Figure S2
26	A1	change	-0.90 percent			68	hypothetical; other; diabetes_duration:11.7_or_more; R0024029:Table 1
26	A1 vs A2	md	-0.80 percent		-1.16 to -0.44		hypothetical; other; diabetes_duration:11.7_or_more; R0024029:Table 1
26	A1 vs A2	md	-0.66 percent		-0.88 to -0.45		hypothetical; full analysis; R0024267:Supplement Figure S2
26	A1	change	-1.12 percent			69	hypothetical; other; diabetes_duration:5.6_to_11.6; R0024029:Table 1
26	A1 vs A2	md	-0.69 percent		-1.04 to -0.33		hypothetical; other; diabetes_duration:5.6_to_11.6; R0024029:Table 1
26	A2	change	-0.32 percent	0.83		100	treatment policy; full analysis; registry:outcomes
26	A2	change	-0.30 percent			100	treatment policy; full analysis; R0024267:Results
26	A2	change	-0.48 percent			40	hypothetical; other; bmi:28.6_to_33.9; R0024029:Table 1
26	A2	change	-0.40 percent			34	hypothetical; other; bmi:34.0_or_more; R0024029:Table 1
26	A2	change	-0.10 percent			26	hypothetical; other; bmi:less_than_28.6; R0024029:Table 1
26	A2	change	-0.11 percent			32	hypothetical; other; diabetes_duration:11.7_or_more; R0024029:Table 1
26	A2	change	-0.44 percent			33	hypothetical; other; diabetes_duration:5.6_to_11.6; R0024029:Table 1
26	A2	change	-0.50 percent			35	hypothetical; other; diabetes_duration:less_than_5.6; R0024029:Table 1
26	A2	change	-0.90 percent			27	hypothetical; other; hba1c:7.0_to_less_than_7.6; R0024029:Table 1
26	A2	change	-0.31 percent			35	hypothetical; other; hba1c:7.6_to_8.1; R0024029:Table 1
26	A2	change	-0.02 percent			38	hypothetical; other; hba1c:8.2_to_9.5; R0024029:Table 1
26	A2	change	-0.28 percent			100	hypothetical; full analysis; R0024267:Supplement Table S3
26	A2	change	-0.35 percent	0.80		100	hypothetical; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (38 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-2.92 kg			203	hypothetical; full analysis; R0024267:Supplement Table S3
26	A1	change	-2.89 kg	3.81		203	hypothetical; full analysis; registry:outcomes
26	A1 vs A2	md	-0.86 kg		-1.77 to -0.04		hypothetical; full analysis; R0024267:Supplement Table S3
26	A1 vs A2	md	-0.86 kg	0.46	-1.77 to 0.04		hypothetical; full analysis; registry:outcomes
26	A1 vs A2	md	-1.26 kg		-2.86 to 0.33		hypothetical; other; hba1c:7.6_to_8.1; R0024029:Table 2
26	A1	change	-2.86 kg			63	hypothetical; other; hba1c:7.6_to_8.1; R0024029:Table 2
26	A1	change	-2.81 kg			203	treatment policy; full analysis; R0024267:Results
26	A1	change	-2.84 kg	3.83		203	treatment policy; full analysis; registry:outcomes
26	A1 vs A2	md	-0.82 kg		-1.73 to 0.09		treatment policy; full analysis; R0024267:Results
26	A1 vs A2	md	0.20 kg		-1.52 to 1.92		hypothetical; other; hba1c:7.0_to_less_than_7.6; R0024029:Table 2
26	A1	change	-3.01 kg			65	hypothetical; other; hba1c:7.0_to_less_than_7.6; R0024029:Table 2
26	A1	change	-2.74 kg			61	hypothetical; other; bmi:28.6_to_33.9; R0024029:Table 2
26	A1 vs A2	md	-0.58 kg		-2.09 to 0.94		hypothetical; other; bmi:28.6_to_33.9; R0024029:Table 2
26	A1 vs A2	md	-1.13 kg		-2.78 to 0.50		hypothetical; other; diabetes_duration:less_than_5.6; R0024029:Table 2
26	A1	change	-3.52 kg			67	hypothetical; other; bmi:34.0_or_more; R0024029:Table 2
26	A1 vs A2	md	-0.80 kg		-2.43 to 0.83		hypothetical; other; bmi:34.0_or_more; R0024029:Table 2
26	A1	change	-2.90 kg			69	hypothetical; other; diabetes_duration:5.6_to_11.6; R0024029:Table 2
26	A1	change	-2.44 kg			75	hypothetical; other; bmi:less_than_28.6; R0024029:Table 2
26	A1 vs A2	md	-1.14 kg		-2.84 to 0.57		hypothetical; other; bmi:less_than_28.6; R0024029:Table 2
26	A1 vs A2	md	-0.55 kg		-2.09 to 0.99		hypothetical; other; diabetes_duration:5.6_to_11.6; R0024029:Table 2
26	A1	change	-2.81 kg			68	hypothetical; other; diabetes_duration:11.7_or_more; R0024029:Table 2
26	A1 vs A2	md	-0.60 kg		-2.21 to 1.02		hypothetical; other; diabetes_duration:11.7_or_more; R0024029:Table 2
26	A1 vs A2	md	-0.96 kg		-2.49 to 0.57		hypothetical; other; hba1c:8.2_to_9.5; R0024029:Table 2
26	A1	change	-2.80 kg			75	hypothetical; other; hba1c:8.2_to_9.5; R0024029:Table 2
26	A1	change	-2.96 kg			66	hypothetical; other; diabetes_duration:less_than_5.6; R0024029:Table 2
26	A2	change	-1.85 kg			38	hypothetical; other; hba1c:8.2_to_9.5; R0024029:Table 2
26	A2	change	-2.06 kg			100	hypothetical; full analysis; R0024267:Supplement Table S3
26	A2	change	-2.09 kg	2.96		100	hypothetical; full analysis; registry:outcomes
26	A2	change	-1.99 kg			100	treatment policy; full analysis; R0024267:Results
26	A2	change	-2.02 kg	3.32		100	treatment policy; full analysis; registry:outcomes
26	A2	change	-2.16 kg			40	hypothetical; other; bmi:28.6_to_33.9; R0024029:Table 2
26	A2	change	-2.73 kg			34	hypothetical; other; bmi:34.0_or_more; R0024029:Table 2
26	A2	change	-1.30 kg			26	hypothetical; other; bmi:less_than_28.6; R0024029:Table 2
26	A2	change	-2.21 kg			32	hypothetical; other; diabetes_duration:11.7_or_more; R0024029:Table 2
26	A2	change	-2.35 kg			33	hypothetical; other; diabetes_duration:5.6_to_11.6; R0024029:Table 2
26	A2	change	-1.83 kg			35	hypothetical; other; diabetes_duration:less_than_5.6; R0024029:Table 2
26	A2	change	-3.21 kg			27	hypothetical; other; hba1c:7.0_to_less_than_7.6; R0024029:Table 2
26	A2	change	-1.59 kg			35	hypothetical; other; hba1c:7.6_to_8.1; R0024029:Table 2

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1 vs A2	or	5.13	2.67 to 9.87		treatment policy; full analysis; R0024267:Supplement Table S5
26	A1	responders			101 / 195	treatment policy; full analysis; R0024267:Supplement Table S5
26	A2	responders			22 / 95	treatment policy; full analysis; R0024267:Supplement Table S5

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 202	not stated; safety; R0024267:Table 2
A1	events	0 / 202	not stated; safety; R0024267:Table 2
A1	events	6 / 202	not stated; safety; R0024267:Table 2
A1	events	18 / 202	not stated; safety; R0024267:Table 2
A2	events	0 / 100	not stated; safety; R0024267:Table 2
A2	events	3 / 100	not stated; safety; R0024267:Table 2
A2	events	8 / 100	not stated; safety; R0024267:Table 2
A2	events	7 / 100	not stated; safety; R0024267:Table 2

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	rate				202	while on treatment; safety; registry:outcomes
	A2	rate				100	while on treatment; safety; registry:outcomes

Systolic blood pressure change (6 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A2	md	0.25 mmHg		-2.51 to 3.00		treatment policy; full analysis; R0024267:Results
26	A1	change	-2.17 mmHg			203	hypothetical; full analysis; R0024267:Supplement Table S3
26	A1 vs A2	md	0.77 mmHg		-2.23 to 3.77		hypothetical; full analysis; R0024267:Supplement Table S3
26	A1	change	-1.95 mmHg	13.42		203	treatment policy; full analysis; registry:outcomes
26	A2	change	-3.35 mmHg	12.36		100	treatment policy; full analysis; registry:outcomes
26	A2	change	-2.94 mmHg			100	hypothetical; full analysis; R0024267:Supplement Table S3

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 202	not stated; safety; R0024267:Results
A1	events	0 / 202	while on treatment; safety; registry:adverse_events
A2	events	1 / 100	not stated; safety; R0024267:Results
A2	events	1 / 100	while on treatment; safety; registry:adverse_events

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 202	not stated; safety; R0024267:Table 2
	A2	events				0 / 100	not stated; safety; R0024267:Table 2

Hospitalization for heart failure (2 lines; O23)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 202	while on treatment; safety; cardiac failure congestive; registry:adverse_events
	A2	events				0 / 100	while on treatment; safety; cardiac failure congestive; registry:adverse_events

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				5 / 202	not stated; safety; R0024267:Table 2
	A2	events				1 / 100	not stated; safety; R0024267:Table 2

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 203	not stated; randomized; R0024267:Supplement Figure S1
A1	events	8 / 202	not stated; safety; R0024267:Table 2
A2	events	2 / 100	not stated; safety; R0024267:Table 2
A2	events	0 / 100	not stated; randomized; R0024267:Supplement Figure S1

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				53 / 202	not stated; safety; R0024267:Table 2
	A2	events				6 / 100	not stated; safety; R0024267:Table 2

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				17 / 202	not stated; safety; R0024267:Table 2
	A2	events				2 / 100	not stated; safety; R0024267:Table 2

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				19 / 202	not stated; safety; R0024267:Table 2
	A2	events				3 / 100	not stated; safety; R0024267:Table 2

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				18 / 202	not stated; safety; R0024267:Table 2
	A2	events				0 / 100	not stated; safety; R0024267:Table 2

Discontinuation due to gastrointestinal adverse events (2 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 203	not stated; randomized; R0024267:Supplement Figure S1
	A2	events				0 / 100	not stated; randomized; R0024267:Supplement Figure S1

Gallbladder and biliary disease (2 lines; O28)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 202	while on treatment; safety; cholecystitis; registry:adverse_events
	A2	events				0 / 100	while on treatment; safety; cholecystitis; registry:adverse_events

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 202	not stated; safety; R0024267:Table 2
	A2	events				0 / 100	not stated; safety; R0024267:Table 2

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 202	not stated; safety; R0024267:Table 2
	A2	events				0 / 100	not stated; safety; R0024267:Table 2