parallel randomized trial

LixiLan-L

A Randomized, 30-week, Active-controlled, Open Label, 2- Treatment Arm, Parallel-group, Multicenter Study Comparing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination to Insulin Glargine With or Without Metformin in Patients With Type 2 Diabetes Mellitus (T2DM)

Type 2 diabetes (adults)NCT02058160S001409

Design

Randomized: 736
Start year: 2014
Treatment: 30 weeks, follow-up 30 weeks
Countries: multinational
Sponsor: Sanofi (industry)
Eligibility: adults with T2D on basal insulin 15 to 40 U/d; HbA1c 7 to 10% and glargine 20 to 50 U 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	Completed treatment
A1	IGlarLixi 2:1 pen subcutaneous once daily titrated iGlarLixi	metformin; lifestyle: not reported	367	366
A2	Insulin glargine Insulin glargine	metformin; lifestyle: not reported	369	365

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
age	mean (years)	59.6	60.3
age	sd (years)	9.4	8.7
asian	n	12	8
black	n	17	21
bmi	mean (kg/m2)	31.33	30.96
bmi	sd (kg/m2)	4.25	4.15
diabetes duration	mean (years)	12.02	12.13
diabetes duration	sd (years)	6.64	6.85
female	n	202	190
hba1c	mean (percent)	8.07	8.08
hba1c	sd (percent)	0.68	0.73
hispanic	n	66	66
other race other	n	1	2
weight region:north_america	mean (kg)	87.6	89.7
weight region:north_america	sd (kg)	14.0	16.1
weight region:rest_of_world	mean (kg)	87.9	86.2
weight region:rest_of_world	sd (kg)	14.6	14.2
white	n	337	338

Analyses this trial contributes to

Results

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

HbA1c change (39 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A2	md	-0.52 percent	0.06	-0.633 to -0.397		not stated; modified itt; registry:outcomes
30	A1 vs A2	md	-0.49 percent	0.12			not stated; other; diabetes_duration:more_than_10.75_to_15.67; R0007711:Figure 1
30	A1	change	-1.08 percent			90	not stated; other; diabetes_duration:more_than_15.67; R0007711:Figure 1
30	A1 vs A2	md	-0.62 percent	0.13			not stated; other; diabetes_duration:more_than_15.67; R0007711:Figure 1
30	A1	change	-1.09 percent			102	not stated; other; diabetes_duration:more_than_7.305_to_10.75; R0007711:Figure 1
30	A1 vs A2	md	-0.47 percent	0.13			not stated; other; diabetes_duration:more_than_7.305_to_10.75; R0007711:Figure 1
30	A1	change	-1.4 percent	0.9		199	not stated; other; hba1c:8_or_more; R0013638:Table 1
30	A1 vs A2	md	-0.5 percent	0.1			not stated; other; hba1c:8_or_more; R0013638:Table 1
30	A1	change	-0.8 percent	0.8		165	not stated; other; hba1c:less_than_8; R0013638:Table 1
30	A1 vs A2	md	-0.5 percent	0.1			not stated; other; hba1c:less_than_8; R0013638:Table 1
30	A1	change	-1.08 percent	1.01		105	not stated; other; region:north_america; R0012665:Table 2
30	A1 vs A2	md	-0.50 percent	0.13			not stated; other; region:north_america; R0012665:Table 3
30	A1	change	-1.10 percent	0.84		261	not stated; other; region:rest_of_world; R0012665:Table 2
30	A1 vs A2	md	-0.51 percent	0.08			not stated; other; region:rest_of_world; R0012665:Table 3
30	A1	change	-1.13 percent	0.057		364	not stated; modified itt; registry:outcomes
30	A1	change	-1.1 percent	0.9		209	not stated; other; bmi:30_or_more; R0013638:Table 1
30	A1 vs A2	md	-0.5 percent	0.1			not stated; other; bmi:30_or_more; R0013638:Table 1
30	A1	change	-1.1 percent	0.9		155	not stated; other; bmi:less_than_30; R0013638:Table 1
30	A1 vs A2	md	-0.6 percent	0.1			not stated; other; bmi:less_than_30; R0013638:Table 1
30	A1	change	-1.1 percent	0.9		198	not stated; other; diabetes_duration:10_or_more; R0013638:Table 1
30	A1 vs A2	md	-0.5 percent	0.1			not stated; other; diabetes_duration:10_or_more; R0013638:Table 1
30	A1	change	-1.07 percent			89	not stated; other; diabetes_duration:7.305_or_less; R0007711:Figure 1
30	A1 vs A2	md	-0.48 percent	0.12			not stated; other; diabetes_duration:7.305_or_less; R0007711:Figure 1
30	A1	change	-1.1 percent	0.9		166	not stated; other; diabetes_duration:less_than_10; R0013638:Table 1
30	A1 vs A2	md	-0.5 percent	0.1			not stated; other; diabetes_duration:less_than_10; R0013638:Table 1
30	A1	change	-1.12 percent			83	not stated; other; diabetes_duration:more_than_10.75_to_15.67; R0007711:Figure 1
30	A2	change	-0.62 percent	0.055		364	not stated; modified itt; registry:outcomes
30	A2	change	-0.66 percent			94	not stated; other; diabetes_duration:7.305_or_less; R0007711:Figure 1
30	A2	change	-0.47 percent			90	not stated; other; diabetes_duration:more_than_15.67; R0007711:Figure 1
30	A2	change	-0.8 percent	0.9		201	not stated; other; hba1c:8_or_more; R0013638:Table 1
30	A2	change	-0.6 percent	0.9		208	not stated; other; bmi:30_or_more; R0013638:Table 1
30	A2	change	-0.6 percent	0.9		150	not stated; other; diabetes_duration:less_than_10; R0013638:Table 1
30	A2	change	-0.57 percent	0.84		91	not stated; other; region:north_america; R0012665:Table 2
30	A2	change	-0.5 percent	0.9		156	not stated; other; bmi:less_than_30; R0013638:Table 1
30	A2	change	-0.51 percent			78	not stated; other; diabetes_duration:more_than_7.305_to_10.75; R0007711:Figure 1
30	A2	change	-0.68 percent			101	not stated; other; diabetes_duration:more_than_10.75_to_15.67; R0007711:Figure 1
30	A2	change	-0.6 percent	0.8		213	not stated; other; diabetes_duration:10_or_more; R0013638:Table 1
30	A2	change	-0.59 percent	0.87		274	not stated; other; region:rest_of_world; R0012665:Table 2
30	A2	change	-0.3 percent	0.8		163	not stated; other; hba1c:less_than_8; R0013638:Table 1

Body weight change in kilograms (diabetes) (39 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-0.4 kg	3.8		105	not stated; other; region:north_america; R0012665:Table 2
30	A1	change	-0.67 kg	0.181		365	not stated; modified itt; registry:outcomes
30	A1 vs A2	md	-1.37 kg	0.224	-1.808 to -0.93		not stated; modified itt; registry:outcomes
30	A1	change	-0.9 kg			210	not stated; other; bmi:30_or_more; R0013638:Figure 2
30	A1 vs A2	md	-1.5 kg				not stated; other; bmi:30_or_more; R0013638:Figure 2
30	A1	change	-0.1 kg			155	not stated; other; bmi:less_than_30; R0013638:Figure 2
30	A1 vs A2	md	-1.1 kg				not stated; other; bmi:less_than_30; R0013638:Figure 2
30	A1	change	-0.4 kg			199	not stated; other; diabetes_duration:10_or_more; R0013638:Figure 2
30	A1 vs A2	md	-1.2 kg				not stated; other; diabetes_duration:10_or_more; R0013638:Figure 2
30	A1	change	-0.5 kg			89	not stated; other; diabetes_duration:7.305_or_less; R0007711:Supplement Figure S3
30	A1 vs A2	md	-1.6 kg	0.4			not stated; other; diabetes_duration:7.305_or_less; R0007711:Supplement Figure S3
30	A1	change	-0.6 kg			166	not stated; other; diabetes_duration:less_than_10; R0013638:Figure 2
30	A1 vs A2	md	-1.5 kg				not stated; other; diabetes_duration:less_than_10; R0013638:Figure 2
30	A1	change	-1.0 kg			83	not stated; other; diabetes_duration:more_than_10.75_to_15.67; R0007711:Supplement Figure S3
30	A1 vs A2	md	-2.0 kg	0.5			not stated; other; diabetes_duration:more_than_10.75_to_15.67; R0007711:Supplement Figure S3
30	A1	change	-0.1 kg			90	not stated; other; diabetes_duration:more_than_15.67; R0007711:Supplement Figure S3
30	A1 vs A2	md	-0.5 kg	0.5			not stated; other; diabetes_duration:more_than_15.67; R0007711:Supplement Figure S3
30	A1	change	-0.5 kg			103	not stated; other; diabetes_duration:more_than_7.305_to_10.75; R0007711:Supplement Figure S3
30	A1 vs A2	md	-1.2 kg	0.4			not stated; other; diabetes_duration:more_than_7.305_to_10.75; R0007711:Supplement Figure S3
30	A1	change	-0.3 kg			199	not stated; other; hba1c:8_or_more; R0013638:Figure 2
30	A1 vs A2	md	-1.1 kg				not stated; other; hba1c:8_or_more; R0013638:Figure 2
30	A1	change	-0.8 kg			166	not stated; other; hba1c:less_than_8; R0013638:Figure 2
30	A1 vs A2	md	-1.7 kg				not stated; other; hba1c:less_than_8; R0013638:Figure 2
30	A1 vs A2	md	-1.58 kg	0.43			not stated; other; region:north_america; R0012665:Table 3
30	A1	change	-0.6 kg	3.0		261	not stated; other; region:rest_of_world; R0012665:Table 2
30	A1 vs A2	md	-1.29 kg	0.26			not stated; other; region:rest_of_world; R0012665:Table 3
30	A2	change	0.6 kg			78	not stated; other; diabetes_duration:more_than_7.305_to_10.75; R0007711:Supplement Figure S3
30	A2	change	0.4 kg			91	not stated; other; diabetes_duration:more_than_15.67; R0007711:Supplement Figure S3
30	A2	change	1.1 kg			101	not stated; other; diabetes_duration:more_than_10.75_to_15.67; R0007711:Supplement Figure S3
30	A2	change	0.7 kg			202	not stated; other; hba1c:8_or_more; R0013638:Figure 2
30	A2	change	0.9 kg			150	not stated; other; diabetes_duration:less_than_10; R0013638:Figure 2
30	A2	change	1.1 kg			94	not stated; other; diabetes_duration:7.305_or_less; R0007711:Supplement Figure S3
30	A2	change	1.0 kg			163	not stated; other; hba1c:less_than_8; R0013638:Figure 2
30	A2	change	0.7 kg	0.178		365	not stated; modified itt; registry:outcomes
30	A2	change	0.8 kg			214	not stated; other; diabetes_duration:10_or_more; R0013638:Figure 2
30	A2	change	1.2 kg	2.9		91	not stated; other; region:north_america; R0012665:Table 2
30	A2	change	1.1 kg			156	not stated; other; bmi:less_than_30; R0013638:Figure 2
30	A2	change	0.7 kg			209	not stated; other; bmi:30_or_more; R0013638:Figure 2
30	A2	change	0.7 kg	2.7		274	not stated; other; region:rest_of_world; R0012665:Table 2

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
30	A1	responders	54.9		366	not stated; modified itt; registry:outcomes
30	A1 vs A2	rd	25.52	18.94 to 32.10		not stated; modified itt; registry:outcomes
30	A2	responders	29.6		365	not stated; modified itt; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (10 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	4 / 365	while on treatment; safety; R0014829:Table 3
A1	events	146 / 365	while on treatment; safety; R0014829:Table 3
A1	events	2 / 365	not stated; safety; registry:adverse_events
A1	events	1 / 365	not stated; safety; hypoglycaemic seizure; registry:adverse_events
A1	events	2 / 365	not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events
A2	events	0 / 365	not stated; safety; hypoglycaemic seizure; registry:adverse_events
A2	events	0 / 365	not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events
A2	events	1 / 365	not stated; safety; registry:adverse_events
A2	events	155 / 365	while on treatment; safety; R0014829:Table 3
A2	events	1 / 365	while on treatment; safety; R0014829:Table 3

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	rate	3.03			365	while on treatment; safety; R0014829:Table 3
	A2	rate	4.22			365	while on treatment; safety; R0014829:Table 3

Hospitalization for heart failure (2 lines; O23)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 365	not stated; safety; cardiac failure congestive; registry:adverse_events
	A2	events				1 / 365	not stated; 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				20 / 365	not stated; safety; registry:adverse_events
	A2	events				18 / 365	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				12 / 367	not stated; randomized; registry:flow
	A2	events				3 / 369	not stated; randomized; registry:flow

Nausea (4 lines; O27A)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		38 / 365	not stated; safety; registry:adverse_events
A1	events	10.4		not stated; other; R0014829:Results and Discussion
A2	events	0.5		not stated; other; R0014829:Results and Discussion
A2	events		2 / 365	not stated; safety; registry:adverse_events

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events	3.6				not stated; other; R0014829:Results and Discussion
	A2	events	0.5				not stated; other; R0014829:Results and Discussion

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events	4.4				not stated; other; R0014829:Results and Discussion
	A2	events	2.7				not stated; other; R0014829:Results and Discussion

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				4 /	not stated; other; R0007711:Results
	A2	events				0 /	not stated; other; R0007711:Results

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 365	not stated; safety; cholecystitis chronic; registry:adverse_events
A1	events	0 / 365	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	1 / 365	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	0 / 365	not stated; safety; cholecystitis chronic; registry:adverse_events

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 /	not stated; other; pancreatitis; R0014829:Results and Discussion
	A2	events				0 /	not stated; other; pancreatitis; R0014829:Results and Discussion

Pancreatic cancer (2 lines; O38)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 /	not stated; other; R0014829:Results and Discussion
	A2	events				0 /	not stated; other; R0014829:Results and Discussion