parallel randomized trial

LIRA-PRIME

Efficacy in Controlling Glycaemia With Victoza® (Liraglutide) as add-on to Metformin vs. OADs as add-on to Metformin After up to 104 Weeks of Treatment in Subjects With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy and Treated in a Primary Care Setting

Type 2 diabetes (adults)NCT02730377S000508

Design

Randomized: 1,991
Start year: 2016
Treatment: 104 weeks, follow-up 105 weeks
Countries: multinational (219 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: adults; HbA1c 7.5 to 9.0 percent; stable metformin monotherapy

Conduct and analysis

Blinding: open label
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: while on treatment
Analysis population: full analysis
Missing data: last on treatment value

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Liraglutide flexible dose injection once daily Liraglutide up to 1.8 mg	metformin; lifestyle: not reported	996	996
A2	Investigator choice oral drug Oral antidiabetic drug chosen by investigator	metformin; lifestyle: not reported	995	995

Baseline characteristics

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

Characteristic	Statistic	Liraglutide flexible dose injection once daily A1	Investigator choice oral drug A2
age	mean (years)	57.6	57.1
age	sd (years)	11.0	10.7
asian	n	149	141
asian	percent	15.0	14.2
black	n	101	106
black	percent	10.1	10.7
bmi	mean (kg/m2)	33.2	33.7
bmi	sd (kg/m2)	7.2	7.6
diabetes duration	mean (years)	7.3	7.1
diabetes duration	sd (years)	5.9	5.9
egfr	mean (mL/min/1.73 m2)	94.7	96.0
egfr	sd (mL/min/1.73 m2)	26.6	26.3
established cvd: macroangiopathy	n	61	41
established cvd: macroangiopathy	percent	6.1	4.1
female	n	476	471
female	percent	47.8	47.3
hba1c	mean (percent)	8.2	8.1
hba1c	sd (percent)	1.0	0.9
hispanic	n	176	189
hispanic	percent	17.7	19.0
other macroangiopathy	n	61	41
other macroangiopathy	percent	6.1	4.1
other race american indian alaska native	n	3	6
other race american indian alaska native	percent	0.3	0.6
other race native hawaiian pacific islander	n	3	2
other race native hawaiian pacific islander	percent	0.3	0.2
other race other	n	16	26
other race other	percent	1.6	2.6
weight	mean (kg)	93.8	95.9
weight	sd (kg)	23.5	25.3
white	n	724	714
white	percent	72.7	71.8

Analyses this trial contributes to

Results

55 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
104	A1	change	-0.99 percent	0.037		872	while on treatment; full analysis; R0022482:Supplement Table S4
104	A1	change	-0.90 percent	0.044		877	while on treatment; full analysis; R0022482:Supplement Table S4
104	A1 vs A2	md	-0.33 percent		-0.43 to -0.23		while on treatment; full analysis; R0022482:Table 2
104	A1 vs A2	md	-0.34 percent		-0.47 to -0.21		while on treatment; full analysis; R0022482:Supplement Table S4
104	A2	change	-0.66 percent	0.036		900	while on treatment; full analysis; R0022482:Supplement Table S4
104	A2	change	-0.57 percent	0.048		901	while on treatment; full analysis; R0022482:Supplement Table S4

Body weight change in kilograms (diabetes) (1 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
104	A1 vs A2	md	-0.61 kg		-1.07 to -0.16		while on treatment; full analysis; R0022482:Table 2

Level 2 or 3 hypoglycemia (participants) (6 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	18 / 980	while on treatment; safety; R0022482:Supplement Table S5
A1	events	1 / 980	while on treatment; safety; R0022482:Supplement Table S5
A1	events	50 / 980	while on treatment; safety; R0022482:Supplement Table S5
A2	events	21 / 984	while on treatment; safety; R0022482:Supplement Table S5
A2	events	6 / 984	while on treatment; safety; R0022482:Supplement Table S5
A2	events	53 / 984	while on treatment; safety; R0022482:Supplement Table S5

Level 2 or 3 hypoglycemia (episode rate) (9 lines; O04B)

Arm	Statistic	Estimate	95% CI	Detail
A1	rate			while on treatment; safety; R0022482:Supplement Table S5
A1 vs A2	rate ratio	0.589	0.310 to 1.118	while on treatment; safety; R0022482:Supplement Table S6
A1	rate			while on treatment; safety; R0022482:Supplement Table S5
A1 vs A2	rate ratio	0.154	0.019 to 1.284	while on treatment; safety; R0022482:Supplement Table S6
A1	rate			while on treatment; safety; R0022482:Supplement Table S5
A1 vs A2	rate ratio	0.607	0.358 to 1.029	while on treatment; safety; R0022482:Supplement Table S6
A2	rate			while on treatment; safety; R0022482:Supplement Table S5
A2	rate			while on treatment; safety; R0022482:Supplement Table S5
A2	rate			while on treatment; safety; R0022482:Supplement Table S5

Systolic blood pressure change (1 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
104	A1 vs A2	md	0.24 mmHg		-0.89 to 1.36		while on treatment; full analysis; R0022482:Table 2

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				6 / 980	not stated; safety; registry:adverse_events
	A2	events				2 / 984	not stated; safety; registry:adverse_events

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 980	not stated; safety; registry:adverse_events
	A2	events				8 / 984	not stated; safety; registry:adverse_events

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				92 / 980	while on treatment; safety; R0022482:Table 3
	A2	events				81 / 984	while on treatment; safety; R0022482:Table 3

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	79 / 996	not stated; randomized; registry:flow
A1	events	77 / 980	while on treatment; safety; R0022482:Supplement Table S7
A2	events	41 / 995	not stated; randomized; registry:flow
A2	events	41 / 984	while on treatment; safety; R0022482:Supplement Table S7

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				65 / 980	not stated; safety; registry:adverse_events
	A2	events				15 / 984	not stated; safety; registry:adverse_events

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 980	not stated; safety; registry:adverse_events
	A2	events				1 / 984	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 980	not stated; safety; registry:adverse_events
	A2	events				0 / 984	not stated; safety; registry:adverse_events

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				54 / 980	while on treatment; safety; R0022482:Supplement Table S7
	A2	events				9 / 984	while on treatment; safety; R0022482:Supplement Table S7

Gallbladder and biliary disease (2 lines; O28)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 980	not stated; safety; cholelithiasis; registry:adverse_events
	A2	events				2 / 984	not stated; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 980	not stated; safety; pancreatitis acute; registry:adverse_events
A1	events	1 / 980	not stated; safety; pancreatitis; registry:adverse_events
A2	events	1 / 984	not stated; safety; pancreatitis acute; registry:adverse_events
A2	events	1 / 984	not stated; safety; pancreatitis; registry:adverse_events

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 980	not stated; safety; papillary thyroid cancer; registry:adverse_events
	A2	events				0 / 984	not stated; safety; papillary thyroid cancer; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 980	not stated; safety; registry:adverse_events
	A2	events				1 / 984	not stated; safety; registry:adverse_events

Intestinal obstruction or ileus (2 lines; O37B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 980	not stated; safety; small intestinal obstruction; registry:adverse_events
	A2	events				0 / 984	not stated; safety; small intestinal obstruction; registry:adverse_events

Any cancer (2 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 980	while on treatment; safety; R0022482:Table 3
	A2	events				10 / 984	while on treatment; safety; R0022482:Table 3