LixiLan-D: Efficacy and Safety of Soliqua Versus Lantus in Ethnically/Racially Diverse Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Agents

• Sponsor: Sanofi (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03434119
• Collaborator: (none)
• Enrollment: 241
• Locations: 85
• Arms: 2
• Actual Duration (Months): 10.5
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Primary Objective:

• To demonstrate the superiority of Soliqua 100/33 versus Lantus in the hemoglobin A1c (HbA1c) change within the overall population.

• To demonstrate the benefit of Soliqua 100/33 versus Lantus in the HbA1c within each ethnic/racial subgroup evaluated (ie, Hispanics of any race, non-Hispanic black/African Americans and non-Hispanic Asians).

Secondary Objective:

• To assess the effects of Soliqua 100/33 versus Lantus on the secondary efficacy parameters within each ethnic/racial subgroup evaluated.

• To assess the change in daily insulin glargine dose within each ethnic/racial subgroup.

• To evaluate the safety and tolerability (e.g., gastrointestinal tolerability) of Soliqua 100/33 versus Lantus within each ethnic/racial subgroup.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Insulin glargine/Lixisenatide; Drug: Insulin glargine (HOE901); Drug: Background therapy	Phase 3

Detailed Description

The study duration was approximately 29 weeks including 2 weeks screening period, 26 weeks open label treatment period, and a 3 days follow-up period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 241 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 26-week Randomized, Open-label, Active-controlled, 2-treatment Arm, Parallel Group Multi-center Study, Comparing the Efficacy and Safety of Soliqua™100/33 Versus Lantus® in Ethnically/Racially Diverse Patients With Type 2 Diabetes Mellitus Inadequately Controlled on Basal Insulin and Oral Antidiabetic Agents
• Actual Study Start Date: Feb 20, 2018
• Actual Primary Completion Date: Jan 7, 2019
• Actual Study Completion Date: Jan 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Soliqua 100/33 Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of oral anti-diabetic drug (OAD) therapy for 26 weeks.	Drug: Insulin glargine/Lixisenatide; Insulin glargine (100 units per milliliter [U/mL]) and lixisenatide (33 micrograms per milliliter [mcg/mL]) self administered by a subcutaneous injection using a prefilled pen. Dose was individually titrated to achieve target fasting self-monitoring of plasma glucose (SMPG) of 80 to 100 milligrams per deciliter (mg/dL) (4.4 to 5.6 millimoles per liter [mmol/L]) while avoiding hypoglycemia.; Other Names: Soliqua 100/33 HOE901/AVE0010 ; Drug: Background therapy; Oral Anti diabetics Drugs (OADs) administered orally according to the locally approved label.
Active Comparator: Lantus Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.	Drug: Insulin glargine (HOE901); Insulin glargine 100 U/mL self-administered by a subcutaneous injection using a prefilled pen. Dose was individually titrated to achieve target fasting SMPG of 80 to 100 mg/dL (4.4 to 5.6 mmol/L) while avoiding hypoglycemia.; Other Names: Lantus HOE901 ; Drug: Background therapy; Oral Anti diabetics Drugs (OADs) administered orally according to the locally approved label.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26 [Baseline, Week 26]

   Change in HbA1c was calculated by subtracting baseline value from Week 26 value.

Secondary Outcome Measures

1. Percentage of Participants Achieving HbA1c Target of <7% at Week 26 [Week 26]

   Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.

2. Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Standardized Mixed Meal at Week 26 [Baseline, Week 26]

   The 2-hour PPG test measured blood glucose 2 hours after eating a standardized breakfast meal.

3. Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test at Week 26 [Baseline, Week 26]

4. Change From Baseline in Daily Insulin Glargine Dose at Week 26 [Baseline, Week 26]

   Change in daily dose was calculated by subtracting baseline value from Week 26 value.

5. Change From Baseline in Body Weight at Week 26 [Baseline, Week 26]

   Change in body weight was calculated by subtracting baseline value from Week 26 value.

6. Percentage of Participants With Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Hypoglycemia) During the On-Treatment Period [Baseline to Week 26]

   Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Documented hypoglycemia with plasma glucose cut-off of <=70 mg/dL (3.9 mmol/L) was any hypoglycemia documented by a measured plasma glucose <=70 mg/dL (3.9 mmol/L) and excluding plasma glucose <54 mg/dL regardless of symptoms. Documented hypoglycemia with plasma glucose cut-off of <54 mg/dL (3.0 mmol/L) was any hypoglycemia documented by a measured plasma glucose <54 mg/dL (3.0 mmol/L) regardless of symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria :

• Participants with type 2 diabetes mellitus (T2DM) diagnosed at least 1 year prior to the screening visit (signing of informed consent).

• Uncontrolled diabetes as demonstrated by a screening centrally measured hemoglobin A1c (HbA1c) between 7.5% and 10% (inclusive).

• Participants who were Hispanics of any race, non-Hispanic black/African Americans or non-Hispanic Asians. Note: Decision for ethnic/racial inclusion was made based on the participant's self-identification. Mixed-race participants must select 1 of the above-mentioned categories. If such selection could not be made, the candidate would be ineligible to participate in the study.

• Participants who had been treated with any basal insulin (ie, glargine - U100 or U300, detemir, degludec, intermediate-acting [human Neutral Protamine Hagedorn (NPH]) for at least 6 months prior to Visit 1.

• The basal insulin regimen (ie, type of insulin and time/frequency of the injection) had been stable for at least 3 months prior to Visit 1.

• The basal insulin dose had been stable (defined as up to ±20% [1/5 of the dose] variability) for at least 2 months prior to Visit 1 within the following dose ranges:

• 15 to 50 units/day if HbA1c at Visit 1 is less than or equal to (<=)8.5%, and

• 15 to 40 units/day if HbA1c at Visit 1 is greater than (>)8.5%.

• Participants receiving 1 or 2 of the following OAD drugs: metformin, pioglitazone/rosiglitazone, an sodium-glucose transport protein 2 (SGLT-2) inhibitor or a sulfonylurea (SU), at stable doses for at least 12 weeks prior to Visit 1.

Exclusion criteria:

• Age <18 years of age at Visit 1.

• A body mass index (BMI) <=20 or >40 kg/m^2 at Visit 1.

• Fasting plasma glucose (FPG) >200 mg/dL (by central lab measurement) at Visit 1 (1-time repeat measurement before Visit 2 is permitted).

• Type 1 DM or any diabetes other than T2DM.

• Any use of OAD drugs other than those described in the inclusion criteria (e.g., but not limited to, glucagon like peptide-1 receptor agonist (GLP-1 RA), dipeptidyl peptidase 4 (DPP4) inhibitors) within 12 weeks prior Visit 1.

• Use of any other type of insulin except for basal insulin (e.g., prandial or premixed insulin, insulin pump) within 6 months prior to Visit 1. Note: History of short-term treatment (i.e, <=10 days) with other insulin types due to intercurrent illness was permitted at the discretion of the Investigator.

• Known history of discontinuation of treatment with a GLP-1 RA due to safety/tolerability reasons.

• Use of systemic glucocorticoids for a total duration of >7 days within 12 weeks prior to Visit 1.

• Initiation/change in type or dose of a weight loss drug within 12 weeks prior to Visit

The above information is not intended to contain all considerations relevant to a participants's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 8400072	Montgomery	Alabama	United States	36106
2	Investigational Site Number 8400077	Little Rock	Arkansas	United States	72204
3	Investigational Site Number 8400095	Little Rock	Arkansas	United States	72205
4	Investigational Site Number 8400013	Little Rock	Arkansas	United States	72211
5	Investigational Site Number 8400076	Anaheim	California	United States	92801-4123
6	Investigational Site Number 8400052	Anaheim	California	United States	92801
7	Investigational Site Number 8400069	Anaheim	California	United States	92805
8	Investigational Site Number 8400060	Burbank	California	United States	91505
9	Investigational Site Number 8400049	Cerritos	California	United States	90703
10	Investigational Site Number 8400078	Chula Vista	California	United States	91910
11	Investigational Site Number 8400047	Escondido	California	United States	92025
12	Investigational Site Number 8400066	Fountain Valley	California	United States	92708
13	Investigational Site Number 8400050	Greenbrae	California	United States	94904
14	Investigational Site Number 8400092	Huntington Park	California	United States	90255
15	Investigational Site Number 8400015	Los Angeles	California	United States	90017
16	Investigational Site Number 8400011	Los Angeles	California	United States	90057
17	Investigational Site Number 8400301	Los Angeles	California	United States	90094
18	Investigational Site Number 8400302	Los Angeles	California	United States	90094
19	Investigational Site Number 8400303	Los Angeles	California	United States	90094
20	Investigational Site Number 8400304	Los Angeles	California	United States	90094
21	Investigational Site Number 8400006	Los Gatos	California	United States	95032
22	Investigational Site Number 8400048	Oakland	California	United States	94612
23	Investigational Site Number 8400053	Orange	California	United States	92868
24	Investigational Site Number 8400084	Pomona	California	United States	91766
25	Investigational Site Number 8400081	Pomona	California	United States	91767
26	Investigational Site Number 8400042	Rancho Cucamonga	California	United States	91730
27	Investigational Site Number 8400063	San Carlos	California	United States	94070
28	Investigational Site Number 8400091	San Diego	California	United States	92114
29	Investigational Site Number 8400086	San Jose	California	United States	95148
30	Investigational Site Number 8400074	Santa Ana	California	United States	92701
31	Investigational Site Number 8400037	Temecula	California	United States	92591
32	Investigational Site Number 8400087	Vallejo	California	United States	94592
33	Investigational Site Number 8400024	Van Nuys	California	United States	91405
34	Investigational Site Number 8400007	Ventura	California	United States	93003
35	Investigational Site Number 8400054	Englewood	Colorado	United States	80113
36	Investigational Site Number 8400023	Hamden	Connecticut	United States	06517
37	Investigational Site Number 8400041	Gainesville	Florida	United States	32653
38	Investigational Site Number 8400075	Jacksonville	Florida	United States	32204
39	Investigational Site Number 8400016	Miami Lakes	Florida	United States	33014
40	Investigational Site Number 8400036	Miami	Florida	United States	33144
41	Investigational Site Number 8400017	Miami	Florida	United States	33176
42	Investigational Site Number 8400014	Ocoee	Florida	United States	34761
43	Investigational Site Number 8400028	Port Charlotte	Florida	United States	33952
44	Investigational Site Number 8400097	Saint Petersburg	Florida	United States	00000
45	Investigational Site Number 8400035	Saint Petersburg	Florida	United States	33713
46	Investigational Site Number 8400094	Tampa	Florida	United States	33634
47	Investigational Site Number 8400025	Atlanta	Georgia	United States	30303
48	Investigational Site Number 8400051	Atlanta	Georgia	United States	30310
49	Investigational Site Number 8400093	Atlanta	Georgia	United States	30318
50	Investigational Site Number 8400005	Savannah	Georgia	United States	31406-2675
51	Investigational Site Number 8400038	Chicago	Illinois	United States	60607
52	Investigational Site Number 8400088	Chicago	Illinois	United States	60607
53	Investigational Site Number 8400031	Des Plaines	Illinois	United States	60018
54	Investigational Site Number 8400064	Evanston	Illinois	United States	60201
55	Investigational Site Number 8400057	Gurnee	Illinois	United States	60031
56	Investigational Site Number 8400030	Gretna	Louisiana	United States	70053
57	Investigational Site Number 8400009	New Orleans	Louisiana	United States	70124
58	Investigational Site Number 8400065	Baltimore	Maryland	United States	21237
59	Investigational Site Number 8400061	Rockville	Maryland	United States	20852
60	Investigational Site Number 8400079	Chelsea	Michigan	United States	48118
61	Investigational Site Number 8400001	Flint	Michigan	United States	48504
62	Investigational Site Number 8400012	Flint	Michigan	United States	48532-3447
63	Investigational Site Number 8400090	Las Vegas	Nevada	United States	89117
64	Investigational Site Number 8400082	Las Vegas	Nevada	United States	89148
65	Investigational Site Number 8400018	Linden	New Jersey	United States	07036
66	Investigational Site Number 8400003	Bronx	New York	United States	10455
67	Investigational Site Number 8400062	Philadelphia	Pennsylvania	United States	19107
68	Investigational Site Number 8400043	Columbia	South Carolina	United States	29204
69	Investigational Site Number 8400021	Dallas	Texas	United States	75230
70	Investigational Site Number 8400040	Fort Worth	Texas	United States	76132
71	Investigational Site Number 8400045	Houston	Texas	United States	77089
72	Investigational Site Number 8400002	Humble	Texas	United States	77338
73	Investigational Site Number 8400039	Kerrville	Texas	United States	78028
74	Investigational Site Number 8400096	Lufkin	Texas	United States	75904
75	Investigational Site Number 8400027	San Antonio	Texas	United States	78228
76	Investigational Site Number 8400083	San Antonio	Texas	United States	78230
77	Investigational Site Number 8400008	Splendora	Texas	United States	77372
78	Investigational Site Number 8400055	Spring	Texas	United States	77379
79	Investigational Site Number 8400070	Sugar Land	Texas	United States	77478
80	Investigational Site Number 8400085	Sugar Land	Texas	United States	77479
81	Investigational Site Number 8400059	Webster	Texas	United States	77598
82	Investigational Site Number 8400044	Manassas	Virginia	United States	20110
83	Investigational Site Number 8400068	Norfolk	Virginia	United States	23510
84	Investigational Site Number 8400033	Richmond	Virginia	United States	23219
85	Investigational Site Number 8400029	Richland	Washington	United States	99352

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Dec 18, 2017
• Statistical Analysis Plan - Feb 28, 2019

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT03434119
• Other Study ID Numbers: LPS14860; U1111-1200-1891
• First Posted: Feb 15, 2018
• Last Update Posted: Mar 28, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine; Lixisenatide

Study Results

Participant Flow

Recruitment Details	The study was conducted at 94 sites in United States (US). A total of 534 participants were screened between 20 February 2018 and 01 November 2018, of which 293 participants were screen failures. Screen failures were mainly due to glycated hemoglobin A1c (HbA1c) level less than (<)7.5% or greater than (>)10% at the screening visit.
Pre-assignment Detail	Randomization was stratified by self-reported ethnic/racial group, screening HbA1c values (<8.5% vs >=8.5%), background use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors (yes/no), background use of sulfonylureas (yes/no). Assignment to arms was done centrally by an interactive response technology (IRT) in 1:1 ratio (Soliqua 100/33:Lantus).

Arm/Group Title	Soliqua 100/33	Lantus
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of oral anti-diabetic drug (OAD) therapy for 26 weeks.	Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.
Period Title: Overall Study
STARTED	116	125
Treated	115	125
COMPLETED	9	12
NOT COMPLETED	107	113

Baseline Characteristics

Arm/Group Title	Soliqua 100/33	Lantus	Total
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of OAD therapy for 26 weeks.	Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.	Total of all reporting groups
Overall Participants	116	125	241
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.6 (9.7)	57.7 (11.9)	59.6 (11.1)
Sex: Female, Male (Count of Participants)
Female	57 49.1%	67 53.6%	124 51.5%
Male	59 50.9%	58 46.4%	117 48.5%
Race/Ethnicity, Customized (Count of Participants)
Hispanics of any race	60 51.7%	64 51.2%	124 51.5%
Non-Hispanic black or African Americans	39 33.6%	40 32%	79 32.8%
Non-Hispanic Asians	17 14.7%	21 16.8%	38 15.8%
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	30.90 (4.74)	30.67 (4.93)	30.78 (4.83)
Duration of Diabetes (Count of Participants)
<10 years	26 22.4%	39 31.2%	65 27%
>=10 years	90 77.6%	86 68.8%	176 73%
Glycated Haemoglobin (HbA1c %) (percentage of hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of hemoglobin]	8.62 (0.74)	8.62 (0.68)	8.62 (0.71)
Body Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	84.97 (15.89)	84.84 (19.34)	84.90 (17.73)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 26
Description	Change in HbA1c was calculated by subtracting baseline value from Week 26 value.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on intent-to-treat (ITT) population that included all randomized participants. Here, overall number of participants analyzed = participants with available data for the specified outcome measure.

Arm/Group Title	Soliqua 100/33	Lantus
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of OAD therapy for 26 weeks.	Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.
Measure Participants	19	26
Mean (Standard Deviation) [percentage of HbA1c]	-1.86 (0.96)	-1.07 (1.17)

2. Secondary Outcome

Title	Percentage of Participants Achieving HbA1c Target of <7% at Week 26
Description	Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for the specified outcome measure.

Arm/Group Title	Soliqua 100/33	Lantus
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of OAD therapy for 26 weeks.	Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.
Measure Participants	19	26
Number [percentage of participants]	52.6 45.3%	30.8 24.6%

3. Secondary Outcome

Title	Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Standardized Mixed Meal at Week 26
Description	The 2-hour PPG test measured blood glucose 2 hours after eating a standardized breakfast meal.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Data were not collected, hence planned analysis was not performed due to early termination of the study.

Arm/Group Title	Soliqua 100/33	Lantus
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of OAD therapy for 26 weeks.	Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.
Measure Participants	0	0

4. Secondary Outcome

Title	Change From Baseline in 2-Hour Blood Glucose Excursion During Standardized Meal Test at Week 26
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Data were not collected, hence planned analysis was not performed due to early termination of the study.

Arm/Group Title	Soliqua 100/33	Lantus
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of OAD therapy for 26 weeks.	Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.
Measure Participants	0	0

5. Secondary Outcome

Title	Change From Baseline in Daily Insulin Glargine Dose at Week 26
Description	Change in daily dose was calculated by subtracting baseline value from Week 26 value.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Soliqua 100/33	Lantus
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of OAD therapy for 26 weeks.	Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.
Measure Participants	9	11
Mean (Standard Deviation) [International Units (IU)]	18.7 (16.4)	14.1 (16.5)

6. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 26
Description	Change in body weight was calculated by subtracting baseline value from Week 26 value.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Soliqua 100/33	Lantus
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of OAD therapy for 26 weeks.	Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.
Measure Participants	18	24
Mean (Standard Deviation) [kilograms (kg)]	1.69 (3.74)	1.52 (2.92)

7. Secondary Outcome

Title	Percentage of Participants With Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Hypoglycemia) During the On-Treatment Period
Description	Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Documented hypoglycemia with plasma glucose cut-off of <=70 mg/dL (3.9 mmol/L) was any hypoglycemia documented by a measured plasma glucose <=70 mg/dL (3.9 mmol/L) and excluding plasma glucose <54 mg/dL regardless of symptoms. Documented hypoglycemia with plasma glucose cut-off of <54 mg/dL (3.0 mmol/L) was any hypoglycemia documented by a measured plasma glucose <54 mg/dL (3.0 mmol/L) regardless of symptoms.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population that included all randomized participants who received at least 1 dose of open-label investigational medicinal product (IMP), regardless of the amount of treatment administered. Participants were analyzed according to the treatment actually received.

Arm/Group Title	Soliqua 100/33	Lantus
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of OAD therapy for 26 weeks.	Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.
Measure Participants	115	125
Any hypoglycemia	48.7 42%	52.8 42.2%
Severe hypoglycemia	1.7 1.5%	2.4 1.9%
Documented hypoglycaemia <=70 mg/dL (3.9 mmol/L)	43.5 37.5%	48.8 39%
Documented hypoglycaemia <54 mg/dL (3.0 mmol/L)	12.2 10.5%	18.4 14.7%

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (maximum treatment exposure: 194 days) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description	Reported AEs and deaths are treatment emergent AEs that is AEs that developed/worsened or became serious and deaths that occurred during the 'on treatment period' (the time from the first injection of IMP up to 3 days after the last injection of IMP, regardless of the introduction of rescue therapy). Analysis was performed on safety population.
Arm/Group Title	Soliqua 100/33		Lantus
Arm/Group Description	Soliqua 100/33 (Insulin glargine/lixisenatide) once daily in the morning within 1 hour before breakfast, on top of OAD therapy for 26 weeks.		Lantus (Insulin glargine) once daily at any time of the day but at about the same time every day on top of OAD therapy for 26 weeks.
All Cause Mortality
	Soliqua 100/33		Lantus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/115 (0%)		0/125 (0%)
Serious Adverse Events
	Soliqua 100/33		Lantus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/115 (6.1%)		4/125 (3.2%)
Blood and lymphatic system disorders
Anaemia	0/115 (0%)	0	1/125 (0.8%)	1
Cardiac disorders
Acute Myocardial Infarction	1/115 (0.9%)	1	0/125 (0%)	0
Angina Unstable	0/115 (0%)	0	1/125 (0.8%)	1
Atrial Fibrillation	1/115 (0.9%)	1	0/125 (0%)	0
Cardiac Failure Congestive	1/115 (0.9%)	1	0/125 (0%)	0
Coronary Artery Disease	1/115 (0.9%)	1	0/125 (0%)	0
Myocardial Infarction	1/115 (0.9%)	1	0/125 (0%)	0
Gastrointestinal disorders
Rectal Haemorrhage	0/115 (0%)	0	1/125 (0.8%)	1
Infections and infestations
Gastroenteritis Viral	0/115 (0%)	0	1/125 (0.8%)	1
Metabolism and nutrition disorders
Hypoglycaemia	1/115 (0.9%)	1	0/125 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive Ductal Breast Carcinoma	1/115 (0.9%)	1	0/125 (0%)	0
Nervous system disorders
Facial Paralysis	1/115 (0.9%)	1	0/125 (0%)	0
Hypoglycaemic Unconsciousness	0/115 (0%)	0	1/125 (0.8%)	1
Psychiatric disorders
Alcohol Withdrawal Syndrome	0/115 (0%)	0	1/125 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/115 (0%)	0	1/125 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Soliqua 100/33		Lantus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/115 (18.3%)		20/125 (16%)
Gastrointestinal disorders
Diarrhoea	8/115 (7%)	13	3/125 (2.4%)	4
Nausea	8/115 (7%)	12	2/125 (1.6%)	2
Vomiting	6/115 (5.2%)	7	2/125 (1.6%)	2
Infections and infestations
Upper Respiratory Tract Infection	3/115 (2.6%)	3	10/125 (8%)	11
Nervous system disorders
Headache	7/115 (6.1%)	11	8/125 (6.4%)	12

Limitations/Caveats

Planned analysis could not be performed due to early study termination.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.