parallel randomized trial

LixiLan-O

A Randomized, 30 Week, Active-controlled, Open-label, 3-treatment Arm, Parallel-group Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination to Insulin Glargine Alone and to Lixisenatide Alone on Top of Metformin in Patients With Type 2 Diabetes Mellitus (T2DM)

Type 2 diabetes (adults)NCT02058147S001199

Design

Randomized: 1,170
Start year: 2014
Treatment: 30 weeks, follow-up 30.29 weeks
Countries: multinational
Sponsor: Sanofi (industry)
Eligibility: adults; HbA1c 7.5 to 10% on metformin or 7 to 9% on metformin plus second OAD; 7 to 10% after run in

Conduct and analysis

Blinding: open label
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: modified itt
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	IGlarLixi 2:1 pen subcutaneous once daily titrated iGlarLixi titrated once daily	metformin; lifestyle: not reported	469	468
A2	Insulin glargine Insulin glargine titrated once daily	metformin; lifestyle: not reported	467	466
A3	Lixisenatide 20 ug subcutaneous once daily Lixi	metformin; lifestyle: not reported	234	233

Baseline characteristics

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

Characteristic	Statistic	IGlarLixi 2:1 pen subcutaneous once daily titrated A1	Insulin glargine A2	Lixisenatide 20 ug subcutaneous once daily A3
age	mean (years)	58.2	58.3	58.7
age	sd (years)	9.5	9.4	8.7
asian	n	8	7	3
asian	percent	1.7	1.5	1.3
black	n	33	33	12
black	percent	7.0	7.1	5.1
bmi: 30 or more	percent	62.9	61.7	67.9
bmi	mean (kg/m2)	31.6	31.7	32.0
bmi	sd (kg/m2)	4.4	4.5	4.4
diabetes duration	mean (years)	8.9	8.7	8.9
diabetes duration	sd (years)	5.5	5.6	6.3
female	n	247	230	101
female	percent	52.7	49.3	43.2
hba1c: 8 or more	percent	55.9	55.7	56.0
hba1c	mean (percent)	8.1	8.1	8.1
hba1c	sd (percent)	0.7	0.7	0.7
hispanic	n	85	87	51
hispanic	percent	18.1	18.6	21.8
other race other	n	11	6	3
other race other	percent	2.3	1.3	1.3
weight	mean (kg)	89.4	89.8	90.8
weight	sd (kg)	17.2	16.3	16.3
white	n	417	421	216
white	percent	88.9	90.1	92.3

Analyses this trial contributes to

Results

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

HbA1c change (48 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A3	md	-0.9 percent	0.1			not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Figure 1
30	A1 vs A3	md	-0.69 percent	0.09			not stated; other; region:rest_of_world; R0012665:Table 3
30	A1	change	-1.2 percent	0.7		222	not stated; other; hba1c:less_than_8; R0012685:Table 1
30	A1	change	-1.9 percent	0.9		245	not stated; other; hba1c:8_or_more; R0012685:Table 1
30	A1 vs A2	md	-0.29 percent	0.07			not stated; other; region:rest_of_world; R0012665:Table 3
30	A1 vs A3	md	-0.8 percent		-0.96 to -0.65		not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A1	change	-2.9 percent			49	not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1
30	A1 vs A2	md	-0.4 percent		-0.81 to -0.04		not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1
30	A1 vs A3	md	-1.2 percent		-1.63 to -0.75		not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1
30	A1	change	-1.5 percent			290	not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A1 vs A3	md	-0.8 percent	0.06	-0.9 to -0.7		not stated; modified itt; R0013783:Supplement Table S2
30	A1	change	-1.6 percent	0.9		173	not stated; other; bmi:less_than_30; R0012685:Table 1
30	A1	change	-1.53 percent	0.87		332	not stated; other; region:rest_of_world; R0012665:Table 2
30	A1	change	-1.6 percent	0.04		467	not stated; modified itt; R0013783:Supplement Table S2
30	A1 vs A2	md	-0.3 percent		-0.43 to -0.18		not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A1 vs A3	md	-0.84 percent	0.12			not stated; other; region:north_america; R0012665:Table 3
30	A1	change	-1.6 percent	0.9		265	not stated; other; diabetes_duration:7_or_more; R0012685:Table 1
30	A1 vs A2	md	-0.3 percent	0.05	-0.4 to -0.2		not stated; modified itt; R0013783:Supplement Table S2
30	A1 vs A2	md	-0.31 percent	0.10			not stated; other; region:north_america; R0012665:Table 3
30	A1	change	-1.5 percent	0.9		202	not stated; other; diabetes_duration:less_than_7; R0012685:Table 1
30	A1	change	-1.5 percent	0.9		294	not stated; other; bmi:30_or_more; R0012685:Table 1
30	A1	change	-1.53 percent	0.91		136	not stated; other; region:north_america; R0012665:Table 2
30	A1	change	-1.9 percent			137	not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Figure 1
30	A1 vs A2	md	-0.3 percent	0.1			not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Figure 1
30	A2	change	-1.24 percent	0.88		311	not stated; other; region:rest_of_world; R0012665:Table 2
30	A2	change	-1.2 percent			287	not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A2	change	-1.3 percent	0.9		286	not stated; other; bmi:30_or_more; R0012685:Table 1
30	A2	change	-1.3 percent	0.04		464	not stated; modified itt; R0013783:Supplement Table S2
30	A2	change	-1.2 percent	0.9		178	not stated; other; bmi:less_than_30; R0012685:Table 1
30	A2	change	-1.3 percent	0.8		254	not stated; other; diabetes_duration:7_or_more; R0012685:Table 1
30	A2	change	-1.2 percent	0.9		210	not stated; other; diabetes_duration:less_than_7; R0012685:Table 1
30	A2	change	-1.6 percent			135	not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Figure 1
30	A2	change	-1.6 percent	0.8		241	not stated; other; hba1c:8_or_more; R0012685:Table 1
30	A2	change	-2.5 percent			55	not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1
30	A2	change	-0.8 percent	0.7		223	not stated; other; hba1c:less_than_8; R0012685:Table 1
30	A2	change	-1.22 percent	0.85		155	not stated; other; region:north_america; R0012665:Table 2
30	A3	change	-1.0 percent			67	not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Figure 1
30	A3	change	-0.7 percent			145	not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A3	change	-0.5 percent	0.9		109	not stated; other; hba1c:less_than_8; R0012685:Table 1
30	A3	change	-0.8 percent	0.8		96	not stated; other; diabetes_duration:less_than_7; R0012685:Table 1
30	A3	change	-0.8 percent	0.9		137	not stated; other; diabetes_duration:7_or_more; R0012685:Table 1
30	A3	change	-0.7 percent	0.8		74	not stated; other; bmi:less_than_30; R0012685:Table 1
30	A3	change	-0.84 percent	0.86		153	not stated; other; region:rest_of_world; R0012665:Table 2
30	A3	change	-0.70 percent	0.89		80	not stated; other; region:north_america; R0012665:Table 2
30	A3	change	-0.9 percent	0.05		233	not stated; modified itt; R0013783:Supplement Table S2
30	A3	change	-1.1 percent	0.8		124	not stated; other; hba1c:8_or_more; R0012685:Table 1
30	A3	change	-0.8 percent	0.9		159	not stated; other; bmi:30_or_more; R0012685:Table 1
30	A3	change	-1.7 percent			29	not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1

Body weight change in kilograms (diabetes) (48 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A3	md	2.3 kg	0.6	1.1 to 3.4		not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Supplement Figure S1
30	A1	change	0.3 kg	4.2		135	not stated; other; region:north_america; R0012665:Table 2
30	A1 vs A2	md	-1.57 kg	0.44			not stated; other; region:north_america; R0012665:Table 3
30	A1 vs A3	md	1.73 kg	0.53			not stated; other; region:north_america; R0012665:Table 3
30	A1	change	-0.5 kg	3.4		332	not stated; other; region:rest_of_world; R0012665:Table 2
30	A1 vs A2	md	-1.28 kg	0.30			not stated; other; region:rest_of_world; R0012665:Table 3
30	A1 vs A3	md	2.21 kg	0.37			not stated; other; region:rest_of_world; R0012665:Table 3
30	A1	change	-0.3 kg	0.2		467	not stated; modified itt; R0013783:Supplement Table S2
30	A1 vs A2	md	-1.4 kg	0.3	-1.9 to -0.9		not stated; modified itt; R0013783:Supplement Table S2
30	A1 vs A3	md	2.0 kg	0.3	1.4 to 2.6		not stated; modified itt; R0013783:Supplement Table S2
30	A1	change	-0.1 kg			290	not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A1 vs A2	md	-1.3 kg		-1.93 to -0.73		not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A1 vs A3	md	2.3 kg		1.51 to 2.99		not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A1	change	-0.6 kg	4.0		294	not stated; other; bmi:30_or_more; R0012685:Table 1
30	A1	change	0.3 kg	2.8		173	not stated; other; bmi:less_than_30; R0012685:Table 1
30	A1	change	-0.4 kg	3.7		265	not stated; other; diabetes_duration:7_or_more; R0012685:Table 1
30	A1	change	-0.3 kg	3.6		202	not stated; other; diabetes_duration:less_than_7; R0012685:Table 1
30	A1	change	0.3 kg			137	not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Supplement Figure S1
30	A1 vs A2	md	-1.4 kg	0.5	-2.3 to -0.4		not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Supplement Figure S1
30	A1	change	-0.7 kg	3.8		222	not stated; other; hba1c:less_than_8; R0012685:Table 1
30	A1	change	0.1 kg	3.5		245	not stated; other; hba1c:8_or_more; R0012685:Table 1
30	A1	change	1.3 kg			49	not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1
30	A1 vs A2	md	-0.8 kg		-2.24 to 0.69		not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1
30	A1 vs A3	md	2.8 kg		1.10 to 4.51		not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1
30	A2	change	1.8 kg	4.1		155	not stated; other; region:north_america; R0012665:Table 2
30	A2	change	0.5 kg	4.3		223	not stated; other; hba1c:less_than_8; R0012685:Table 1
30	A2	change	1.6 kg			135	not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Supplement Figure S1
30	A2	change	2.0 kg	3.4		178	not stated; other; bmi:less_than_30; R0012685:Table 1
30	A2	change	0.6 kg	4.4		287	not stated; other; bmi:30_or_more; R0012685:Table 1
30	A2	change	0.75 kg	4.1		311	not stated; other; region:rest_of_world; R0012665:Table 2
30	A2	change	1.2 kg	3.7		255	not stated; other; diabetes_duration:7_or_more; R0012685:Table 1
30	A2	change	1.3 kg			286	not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A2	change	2.0 kg			55	not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1
30	A2	change	1.0 kg	4.5		210	not stated; other; diabetes_duration:less_than_7; R0012685:Table 1
30	A2	change	1.1 kg	0.2		465	not stated; modified itt; R0013783:Supplement Table S2
30	A2	change	1.6 kg	3.8		242	not stated; other; hba1c:8_or_more; R0012685:Table 1
30	A3	change	-1.5 kg			29	not stated; modified itt; hba1c:9_or_more; R0015993:Figure 1
30	A3	change	-2.3 kg	0.3		233	not stated; modified itt; R0013783:Supplement Table S2
30	A3	change	-2.3 kg			145	not stated; modified itt; background:prior_second_oad; R0015993:Figure 1
30	A3	change	-2.6 kg	3.6		159	not stated; other; bmi:30_or_more; R0012685:Table 1
30	A3	change	-1.8 kg	2.7		74	not stated; other; bmi:less_than_30; R0012685:Table 1
30	A3	change	-2.4 kg	3.8		137	not stated; other; diabetes_duration:7_or_more; R0012685:Table 1
30	A3	change	-2.1 kg	2.8		96	not stated; other; diabetes_duration:less_than_7; R0012685:Table 1
30	A3	change	-2.0 kg			67	not stated; modified itt; hba1c:8_or_more_prior_second_oad; R0013783:Supplement Figure S1
30	A3	change	-2.1 kg	3.2		124	not stated; other; hba1c:8_or_more; R0012685:Table 1
30	A3	change	-2.6 kg	3.6		109	not stated; other; hba1c:less_than_8; R0012685:Table 1
30	A3	change	-1.48 kg	3.2		80	not stated; other; region:north_america; R0012665:Table 2
30	A3	change	-2.74 kg	3.4		153	not stated; other; region:rest_of_world; R0012665:Table 2

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
30	A1 vs A3	rd	40.6	33.6 to 47.6		not stated; modified itt; R0013783:Supplement Table S2
30	A1	responders			345 / 468	not stated; modified itt; R0013783:Supplement Table S2
30	A1 vs A2	rd	14.3	8.4 to 20.3		not stated; modified itt; R0013783:Supplement Table S2
30	A2	responders			277 / 466	not stated; modified itt; R0013783:Supplement Table S2
30	A3	responders			77 / 233	not stated; modified itt; R0013783:Supplement Table S2

Level 2 or 3 hypoglycemia (participants) (9 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 469	while on treatment; safety; R0014829:Table 3
A1	events	38 / 469	while on treatment; safety; R0015993:Table 1
A1	events	120 / 469	while on treatment; safety; R0013783:Supplement Table S2
A2	events	1 / 467	while on treatment; safety; R0014829:Table 3
A2	events	32 / 467	while on treatment; safety; R0015993:Table 1
A2	events	110 / 467	while on treatment; safety; R0013783:Supplement Table S2
A3	events	4 / 233	while on treatment; safety; R0015993:Table 1
A3	events	0 / 233	while on treatment; safety; R0014829:Table 3
A3	events	15 / 233	while on treatment; safety; R0013783:Supplement Table S2

Level 2 or 3 hypoglycemia (episode rate) (6 lines; O04B)

Arm	Statistic	Estimate	Events / N	Detail
A1	rate	0.24	469	while on treatment; safety; R0015993:Table 1
A1	rate	1.4	469	while on treatment; safety; R0013783:Supplement Table S2
A2	rate	1.2	467	while on treatment; safety; R0013783:Supplement Table S2
A2	rate	0.14	467	while on treatment; safety; R0015993:Table 1
A3	rate	0.06	233	while on treatment; safety; R0015993:Table 1
A3	rate	0.3	233	while on treatment; safety; R0013783:Supplement Table S2

Acute kidney injury (3 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 469	not stated; safety; registry:adverse_events
A2	events	0 / 467	not stated; safety; registry:adverse_events
A3	events	1 / 233	not stated; safety; registry:adverse_events

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 469	not stated; safety; death; registry:adverse_events
A2	events	0 / 467	not stated; safety; death; registry:adverse_events
A3	events	1 / 233	not stated; safety; R0014829:Table 1

Hospitalization for heart failure (9 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 469	not stated; safety; cardiac failure chronic; registry:adverse_events
A1	events	0 / 469	not stated; safety; cardiac failure acute; registry:adverse_events
A1	events	1 / 469	not stated; safety; cardiac failure congestive; registry:adverse_events
A2	events	1 / 467	not stated; safety; cardiac failure chronic; registry:adverse_events
A2	events	1 / 467	not stated; safety; cardiac failure acute; registry:adverse_events
A2	events	1 / 467	not stated; safety; cardiac failure congestive; registry:adverse_events
A3	events	0 / 233	not stated; safety; cardiac failure congestive; registry:adverse_events
A3	events	0 / 233	not stated; safety; cardiac failure acute; registry:adverse_events
A3	events	0 / 233	not stated; safety; cardiac failure chronic; registry:adverse_events

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	18 / 469	not stated; safety; registry:adverse_events
A2	events	19 / 467	not stated; safety; registry:adverse_events
A3	events	9 / 233	not stated; safety; R0014829:Table 1

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	12 / 469	not stated; randomized; registry:flow
A2	events	9 / 467	not stated; randomized; registry:flow
A3	events	21 / 233	not stated; safety; R0014829:Table 1

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	45 / 469	not stated; safety; R0015993:Table 1
A2	events	17 / 467	not stated; safety; R0015993:Table 1
A3	events	56 / 233	not stated; safety; R0015993:Table 1

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	15 / 469	not stated; safety; R0015993:Table 1
A2	events	7 / 467	not stated; safety; R0015993:Table 1
A3	events	15 / 233	not stated; safety; R0015993:Table 1

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	42 / 469	not stated; safety; R0015993:Table 1
A2	events	20 / 467	not stated; safety; R0015993:Table 1
A3	events	21 / 233	not stated; safety; R0015993:Table 1

Discontinuation due to gastrointestinal adverse events (11 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	1 / 469	not stated; safety; diarrhoea; R0015993:Table 1
A1	events	2 / 469	not stated; safety; nausea; R0015993:Table 1
A1	events	2 / 469	not stated; safety; vomiting; R0015993:Table 1
A2	events	0 /	not stated; other; R0014110:Results
A2	events	0 / 467	not stated; safety; diarrhoea; R0015993:Table 1
A2	events	0 / 467	not stated; safety; nausea; R0015993:Table 1
A2	events	0 / 467	not stated; safety; vomiting; R0015993:Table 1
A3	events	12 / 233	not stated; safety; R0014829:Table 2
A3	events	2 / 233	not stated; safety; diarrhoea; R0015993:Table 1
A3	events	6 / 233	not stated; safety; nausea; R0015993:Table 1
A3	events	4 / 233	not stated; safety; vomiting; R0015993:Table 1

Gallbladder and biliary disease (3 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 469	not stated; safety; cholecystitis chronic; registry:adverse_events
A2	events	0 / 467	not stated; safety; cholecystitis chronic; registry:adverse_events
A3	events	0 / 233	not stated; safety; cholecystitis chronic; registry:adverse_events

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Detail
A1	events	not stated; other; pancreatitis; R0014829:Results
A2	events	not stated; other; pancreatitis; R0014829:Results
A3	events	not stated; other; pancreatitis; R0014829:Results

Pancreatic cancer (4 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	0 / 469	not stated; safety; registry:adverse_events
A2	events	1 /	not stated; other; R0014829:Results
A2	events	1 / 467	not stated; safety; registry:adverse_events
A3	events	0 / 233	not stated; safety; registry:adverse_events