parallel randomized trial

LixiLan-G

A 26-Week Randomized, Open-label, Active Controlled, Parallel-group, Study Assessing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and Metformin (Alone or With Pioglitazone and/or SGLT2 Inhibitors), Followed by a Fixed Ratio Combination Single-arm 26-Week Extension Period

Type 2 diabetes (adults)NCT02787551S001125

Design

Randomized: 514
Start year: 2016
Treatment: 26 weeks, follow-up 26 weeks
Countries
Sponsor: Sanofi (industry)
Eligibility: T2D 1 year or more; HbA1c 7 to 9 percent; BMI over 20 to 40; maximum tolerated GLP-1 RA plus metformin

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	insulin glargine and lixisenatide (iGlarLixi) iGlarLixi	metformin with or without pioglitazone or SGLT2 inhibitor; lifestyle: not reported	257	252	230
A2	GLP-1 receptor agonist (liraglutide, exenatide, exenatide ER, albiglutide or dulaglutide) Continued GLP-1 RA	metformin with or without pioglitazone or SGLT2 inhibitor; lifestyle: not reported	257	253	246

Baseline characteristics

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

Characteristic	Statistic	iGlarLixi A1	Continued GLP-1 RA A2
age	mean (years)	59.2	60.0
age	sd (years)	9.6	10.3
asian	n	3	4
black	n	12	7
bmi: 30 or more	n	186	188
bmi: less than 30	n	71	69
bmi	mean (kg/m2)	32.8	32.9
bmi	sd (kg/m2)	4.4	4.4
diabetes duration	mean (years)	11.23	10.95
diabetes duration	sd (years)	7.42	6.08
egfr	mean (mL/min/1.73 m2)	89	86
egfr	sd (mL/min/1.73 m2)	25	23
female	n	131	113
hba1c	mean (percent)	7.78	7.80
hba1c	sd (percent)	0.62	0.56
other race american indian alaska native	n	0	0
other race native hawaiian pacific islander	n	1	0
uacr	median (mg/g)	11	10
weight	mean (kg)	94	95
weight	sd (kg)	16	18
white	n	241	244

Analyses this trial contributes to

Results

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

HbA1c change (11 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.02 percent	0.048		250	not stated; modified itt; registry:outcomes
26	A1	final	6.6 percent	0.7			not stated; modified itt; hba1c:more_than_7.5_to_8.0; R0003966:Results
26	A1 vs A2	md	-0.64 percent	0.067	-0.770 to -0.508		not stated; modified itt; registry:outcomes
26	A1	final	7.0 percent	0.8			not stated; modified itt; hba1c:more_than_8.0_to_9.0; R0003966:Results
26	A1	change	-0.99 percent	0.79		189	not stated; other; R0006249:Table 2
26	A1	final	6.6 percent	0.7			not stated; modified itt; hba1c:7.0_to_7.5; R0003966:Results
26	A2	final	7.7 percent	0.9			not stated; modified itt; hba1c:more_than_8.0_to_9.0; R0003966:Results
26	A2	change	-0.34 percent	0.79		162	not stated; other; R0006249:Table 2
26	A2	change	-0.38 percent	0.048		253	not stated; modified itt; registry:outcomes
26	A2	final	7.2 percent	0.6			not stated; modified itt; hba1c:7.0_to_7.5; R0003966:Results
26	A2	final	7.3 percent	0.7			not stated; modified itt; hba1c:more_than_7.5_to_8.0; R0003966:Results

Body weight change in kilograms (diabetes) (4 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	1.7 kg	3.9	189	not stated; other; R0006249:Table 2
26	A1	change	1.89 kg	0.222	251	not stated; modified itt; registry:outcomes
26	A2	change	-1.4 kg	3.1	162	not stated; other; R0006249:Table 2
26	A2	change	-1.14 kg	0.220	253	not stated; modified itt; registry:outcomes

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	responders	61.9		252	not stated; modified itt; registry:outcomes
26	A1 vs A2	rd	36.05	28.11 to 43.99		not stated; modified itt; registry:outcomes
26	A2	responders	25.7		253	not stated; modified itt; registry:outcomes

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 255	not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events
	A2	events				0 / 256	not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events

Level 2 or 3 hypoglycemia (episode rate) (4 lines; O04B)

Arm	Statistic	Estimate	Events / N	Detail
A1	rate	0.25	255	not stated; safety; registry:outcomes
A1	rate	1.54	255	not stated; safety; registry:outcomes
A2	rate	0.01	256	not stated; safety; registry:outcomes
A2	rate	0.08	256	not stated; safety; registry:outcomes

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 255	not stated; safety; registry:adverse_events
	A2	events				1 / 256	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				0 / 255	not stated; safety; registry:adverse_events
	A2	events				0 / 256	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				10 / 255	not stated; safety; R0003966:Results
	A2	events				9 / 256	not stated; safety; R0003966:Results

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				10 / 257	not stated; randomized; registry:flow
	A2	events				0 / 257	not stated; randomized; registry:flow

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				22 / 255	not stated; safety; registry:adverse_events
	A2	events				6 / 256	not stated; safety; registry:adverse_events

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				14 / 255	not stated; safety; registry:adverse_events
	A2	events				6 / 256	not stated; safety; registry:adverse_events

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 255	not stated; safety; papillary thyroid cancer; registry:adverse_events
	A2	events				0 / 256	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 / 255	not stated; safety; registry:adverse_events
	A2	events				0 / 256	not stated; safety; registry:adverse_events