parallel randomized trial

Lixilan-O-AP

A Randomized, 24 Week, Active-controlled, Open-label, 3-arm, Parallel-group Multicenter Study Comparing the Efficacy and Safety of iGlarLixi to Insulin Glargine and Lixisenatide in Type 2 Diabetes Mellitus Patients Insufficiently Controlled With Oral Antidiabetic Drug(s)

Type 2 diabetes (adults)NCT03798054S000170

Design

Randomized: 878
Start year: 2019
Treatment: 24 weeks, follow-up 24.43 weeks
Countries: China, Korea, Malaysia, Taiwan, Hong Kong (77 sites)
Sponsor: Sanofi (industry)
Eligibility: adults with T2D on metformin with or without a second OAD; HbA1c 7.5 to 11 percent, or 7 to 10 percent with a non SGLT2i second OAD

Conduct and analysis

Blinding: open label
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: treatment policy
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 with or without SGLT2 inhibitor; lifestyle: not reported	351	348	324
A2	Insulin glargine Insulin glargine 100 U/mL	metformin with or without SGLT2 inhibitor; lifestyle: not reported	350	349	322
A3	Lixisenatide 20 ug subcutaneous once daily Lixisenatide	metformin with or without SGLT2 inhibitor; lifestyle: not reported	177	175	148

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)	55.4	56.5	56.3
age	sd (years)	9.1	9.8	10.0
bmi: 24 or more	n	247	229	136
bmi: 24 or more	percent	70.4	65.4	76.8
bmi	mean (kg/m2)	26.10	25.92	26.12
bmi	sd (kg/m2)	3.63	3.92	3.38
diabetes duration	mean (years)	8.03	8.89	8.93
diabetes duration	sd (years)	5.40	5.71	5.23
female	n	171	164	81
female	percent	48.7	46.9	45.8
hba1c: 8 or more	n	223	223	113
hba1c: 8 or more	percent	63.5	63.7	63.8
hba1c	mean (percent)	8.4	8.3	8.3
hba1c	sd (percent)	0.9	0.8	0.9
metformin use	n	351	350	177
metformin use	percent	100.0	100.0	100.0
sglt2i use	n	14	16	8
sglt2i use	percent	4.0	4.6	4.5
weight	mean (kg)	70.6	70.2	71.0
weight	sd (kg)	12.6	13.6	11.8

Analyses this trial contributes to

Results

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

HbA1c change (8 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Detail
24	A1	final	6.3 percent	0.6		treatment policy; modified itt; R0013321:Table 2
24	A1	change	-1.9 percent	0.04		treatment policy; modified itt; R0013321:Table 2
24	A1 vs A2	md	-0.45 percent		-0.55 to -0.35	treatment policy; modified itt; R0013321:Table 2
24	A1 vs A3	md	-0.96 percent		-1.08 to -0.83	treatment policy; modified itt; R0013321:Table 2
24	A2	final	6.8 percent	0.6		treatment policy; modified itt; R0013321:Table 2
24	A2	change	-1.4 percent	0.04		treatment policy; modified itt; R0013321:Table 2
24	A3	change	-0.9 percent	0.06		treatment policy; modified itt; R0013321:Table 2
24	A3	final	7.3 percent	1.0		treatment policy; modified itt; R0013321:Table 2

Body weight change in kilograms (diabetes) (11 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Detail
24	A1 vs A2	md	-1.09 kg		-1.50 to -0.68	treatment policy; modified itt; R0013321:Table 2
24	A1	change	0.03 kg	0.16		treatment policy; modified itt; R0013321:Table 2
24	A1	change	0.10 kg			treatment policy; modified itt; R0013321:Figure 1F
24	A1	final	70.9 kg	13.1		treatment policy; modified itt; R0013321:Table 2
24	A1 vs A3	md	1.73 kg		1.22 to 2.24	treatment policy; modified itt; R0013321:Table 2
24	A2	change	1.20 kg			treatment policy; modified itt; R0013321:Figure 1F
24	A2	change	1.12 kg	0.16		treatment policy; modified itt; R0013321:Table 2
24	A2	final	71.1 kg	13.5		treatment policy; modified itt; R0013321:Table 2
24	A3	change	-1.66 kg			treatment policy; modified itt; R0013321:Figure 1F
24	A3	change	-1.70 kg	0.22		treatment policy; modified itt; R0013321:Table 2
24	A3	final	69.3 kg	11.5		treatment policy; modified itt; R0013321:Table 2

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
24	A1 vs A2	rd	18.6	12.1 to 25.1		treatment policy; modified itt; R0013321:Table 2
24	A1 vs A3	rd	49.5	42.0 to 57.1		treatment policy; modified itt; R0013321:Table 2
24	A1	responders			275 / 348	treatment policy; modified itt; R0013321:Table 2
24	A2	responders			211 / 349	treatment policy; modified itt; R0013321:Table 2
24	A3	responders			52 / 175	treatment policy; modified itt; R0013321:Table 2

Level 2 or 3 hypoglycemia (participants) (13 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	43 / 348	not stated; safety; R0009006:Table 1
A1	events	23 / 348	not stated; safety; R0013321:Table 3
A1	events	1 / 348	not stated; safety; R0009006:Table 1
A1	events	1 / 348	not stated; safety; R0013321:Table 3
A1	events	171 / 348	not stated; safety; R0013321:Table 3
A2	events	0 / 349	not stated; safety; R0009006:Table 1
A2	events	161 / 349	not stated; safety; R0013321:Table 3
A2	events	1 / 349	not stated; safety; R0013321:Table 3
A2	events	10 / 349	not stated; safety; R0013321:Table 3
A2	events	39 / 349	not stated; safety; R0009006:Table 1
A3	events	12 / 176	not stated; safety; R0013321:Table 3
A3	events	1 / 176	not stated; safety; R0013321:Table 3
A3	events	2 / 176	not stated; safety; R0013321:Table 3

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

Arm	Statistic	Estimate	Events / N	Detail
A1	rate	0.19	348	not stated; safety; R0013321:Table 3
A1	rate	3.38	348	not stated; safety; R0013321:Table 3
A1	rate	0.01	348	not stated; safety; R0013321:Table 3
A2	rate	0.06	349	not stated; safety; R0013321:Table 3
A2	rate	3.38	349	not stated; safety; R0013321:Table 3
A2	rate	0.01	349	not stated; safety; R0013321:Table 3
A3	rate	0.27	176	not stated; safety; R0013321:Table 3
A3	rate	0.03	176	not stated; safety; R0013321:Table 3
A3	rate	0.01	176	not stated; safety; R0013321:Table 3

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 348	not stated; safety; R0013321:Results
A2	events	0 / 349	not stated; safety; R0013321:Results
A3	events	1 / 176	not stated; safety; R0013321:Results

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	17 / 348	not stated; safety; R0013321:Table 3
A2	events	20 / 349	not stated; safety; R0013321:Table 3
A3	events	11 / 176	not stated; safety; R0013321:Table 3

Discontinuation due to adverse events (15 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	5 / 348	not stated; safety; nausea; R0013321:Table 3
A1	events	7 / 348	not stated; safety; R0013321:Supplement Figure S2
A1	events	13 / 348	not stated; safety; R0013321:Table 3
A1	events	1 / 348	not stated; safety; diarrhea; R0013321:Table 3
A1	events	1 / 348	not stated; safety; vomiting; R0013321:Table 3
A2	events	3 / 349	not stated; safety; R0013321:Supplement Figure S2
A2	events	3 / 349	not stated; safety; R0013321:Table 3
A2	events	0 / 349	not stated; safety; diarrhea; R0013321:Table 3
A2	events	0 / 349	not stated; safety; nausea; R0013321:Table 3
A2	events	0 / 349	not stated; safety; vomiting; R0013321:Table 3
A3	events	4 / 176	not stated; safety; vomiting; R0013321:Table 3
A3	events	18 / 176	not stated; safety; R0013321:Table 3
A3	events	0 / 176	not stated; safety; diarrhea; R0013321:Table 3
A3	events	5 / 176	not stated; safety; R0013321:Supplement Figure S2
A3	events	3 / 176	not stated; safety; nausea; R0013321:Table 3

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	48 / 348	not stated; safety; R0013321:Table 3
A2	events	2 / 349	not stated; safety; R0013321:Table 3
A3	events	36 / 176	not stated; safety; R0013321:Table 3

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	21 / 348	not stated; safety; R0013321:Table 3
A2	events	1 / 349	not stated; safety; R0013321:Table 3
A3	events	19 / 176	not stated; safety; R0013321:Table 3

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	22 / 348	not stated; safety; R0013321:Table 3
A2	events	8 / 349	not stated; safety; R0013321:Table 3
A3	events	12 / 176	not stated; safety; R0013321:Table 3

Discontinuation due to gastrointestinal adverse events (9 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	1 / 348	not stated; safety; diarrhea; R0013321:Table 3
A1	events	5 / 348	not stated; safety; nausea; R0013321:Table 3
A1	events	1 / 348	not stated; safety; vomiting; R0013321:Table 3
A2	events	0 / 349	not stated; safety; diarrhea; R0013321:Table 3
A2	events	0 / 349	not stated; safety; nausea; R0013321:Table 3
A2	events	0 / 349	not stated; safety; vomiting; R0013321:Table 3
A3	events	0 / 176	not stated; safety; diarrhea; R0013321:Table 3
A3	events	3 / 176	not stated; safety; nausea; R0013321:Table 3
A3	events	4 / 176	not stated; safety; vomiting; R0013321:Table 3

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 348	not stated; safety; pancreatitis; R0013321:Results
A2	events	0 / 349	not stated; safety; pancreatitis; R0013321:Results
A3	events	0 / 176	not stated; safety; pancreatitis; R0013321:Results

Death by suicide (3 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 348	not stated; safety; R0013321:Results
A2	events	0 / 349	not stated; safety; R0013321:Results
A3	events	0 / 176	not stated; safety; R0013321:Results