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LixiLan-O

CompletedPhase 3Results posted

Efficacy and Safety of Insulin Glargine/ Lixisenatide Fixed Ratio Combination Compared to Insulin Glargine Alone and Lixisenatide Alone on Top of Metformin in Patients With T2DM

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)

Lead sponsor

Sanofi

Asset

Lixisenatide

Subcutaneous · GLP-1 agonist

Listed sites

273

Recruiting sites

—

Enrollment

1,170

actual

Study population

Type 2 diabetes

Key I/E criterion

—

Primary endpoint

•HbA1c, change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT02058147

Org study IDEFC12404

Secondary ID2013-003131-30

Secondary IDU1111-1148-4334UTN

Timeline

Milestones

Study first posted2014-02-07estimated

Results first posted2017-02-10actual

Last update posted2017-05-09actual

Study start2014-02 (month precision)

Primary completion2015-06actual (month precision)

Study completion2015-06actual (month precision)

Assets

Investigational agents

Lixisenatide

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Participants with type 2 diabetes mellitus diagnosed for at least 1 year before the screening visit, treated for at least 3 months prior to visit 1 with metformin alone or metformin and a second oral anti-diabetic treatment that could be a sulfonylurea, a glinide, a sodium glucose co-transporter-2 inhibitor or a di-peptidyl peptidase 4 (DPP-4) inhibitors, and who were not adequately controlled with this treatment.

•Signed written informed consent.

Exclusion criteria

•HbA1c at screening visit:

–less than 7.5% or more than 10% for participants previously treated with metformin alone,

–less than 7.0% or more than 9% for participants previously treated with metformin and a second oral anti-diabetic treatment.

•Pregnancy or lactation, women of childbearing potential with no effective contraceptive method.

•Use of oral glucose-lowering agents other than those stated in the inclusion criteria or any injectable glucose-lowering agents during the 3 months before screening.

•Previous Treatment with insulin (except for short-term treatment due to intercurrent illness including gestational diabetes, at the discretion of the trial physician).

•History of discontinuation of a previous treatment with a glucagon-like peptide (GLP-1) receptor agonist (GLP-1 RA) due to safety/tolerability issue or lack of efficacy.

•Participant who previously participated in any clinical trial with lixisenatide or the insulin glargine/lixisenatide fixed ratio combination or had previously received lixisenatide.

•Any contraindication to metformin use, according to local labeling.

•Use of weight loss drugs within 3 months prior to screening visit.

•Within the last 6 months prior to screening visit: history of stroke, myocardial infarction, unstable angina, or heart failure requiring hospitalization. Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period.

•History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy was already performed), chronic pancreatitis, pancreatitis during a previous treatment with incretin therapies, pancreatectomy, stomach/gastric surgery.

•Personal or immediate family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g, multiple endocrine neoplasia syndromes).

•Uncontrolled or inadequately controlled hypertension (systolic blood pressure above 180 mmHg or diastolic blood pressure above 95 mmHg) at screening visit.

•At screening visit, Body Mass Index (BMI) less than or equal to 20 or above 40 kg/m^2.

•At screening visit amylase and/or lipase more than 3 times the upper limit of the normal (ULN) laboratory range.

•At screening visit alanine aminotransferase (ALT) or alkaline phosphatase (AST) more than 3 ULN.

•At screening visit calcitonin above or equal to 20 pg/mL (5.9 pmol/L).

Exclusion Criteria for randomization at the end of the screening period:

•HbA1c less than 7% or above 10%;

•Fasting Plasma glucose above 250 mg/dL (13.9 mmol/L);

•Metformin maximal tolerated dose less than 1500 mg/day;

•Amylase and/or lipase more than 3 ULN.

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

Endpoints (15)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes

Safety / tolerability / PK

Weight & body composition

1 endpoint

Secondary/protocol endpoint

Change in Body Weight From Baseline to Week 30

Time frame:Baseline, Week 30

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), kg	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	-0.29	—
Insulin Glargine	1.11	—
Lixisenatide	-2.3	—

LS Mean Difference-1.495% CI-1.891 – -0.91p<0.0001Mixed Models Analysis

Glycemic / diabetes

11 endpoints

Primary/protocol endpoint

Change in HbA1c From Baseline to Week 30

Time frame:Baseline, Week 30

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), percentage of hemoglobin	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	-1.63	—
Insulin Glargine	-1.34	—
Lixisenatide	-0.85	—

Least Square (LS) Mean Difference-0.7895% CI-0.898 – -0.665p<0.0001Mixed Models Analysis

LS Mean Difference-0.2995% CI-0.384 – -0.194Mixed Models Analysis

LS Mean Difference-0.2995% CI-0.384 – -0.194p<0.0001Mixed Models Analysis

Secondary/protocol endpoint

Percentage of Participants With HbA1c <7.0% or ≤6.5% at Week 30

Time frame:Week 30

HbA1c <7.0% achievement

threshold achievement, improvement

componentsHbA1c <7.0% achievement, HbA1c <6.5% achievement

LOINC 4548-4

Posted result

Group	Value (number), percentage of participants	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio CombinationHbA1c <7.0%	73.7	—
HbA1c ≤6.5%	55.8	—
Insulin GlargineHbA1c <7.0%	59.4	—
HbA1c ≤6.5%	39.5	—
LixisenatideHbA1c <7.0%	33	—
HbA1c ≤6.5%	19.3	—

Difference in percentage40.6195% CI33.63 – 47.59p<0.0001Cochran-Mantel-Haenszel

Difference in percentage36.3895% CI29.81 – 42.95p<0.0001Cochran-Mantel-Haenszel

Difference in percentage14.3195% CI8.37 – 20.25p<0.0001Cochran-Mantel-Haenszel

Difference in percentage16.3595% CI10.13 – 22.58p<0.0001Cochran-Mantel-Haenszel

Secondary/protocol endpoint

Change in Plasma Glucose Excursion From Baseline to Week 30

Time frame:Baseline, Week 30

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mmol/L	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	-2.31	—
Insulin Glargine	-0.18	—
Lixisenatide	-3.23	—

LS Mean Difference-2.1395% CI-2.498 – -1.77p<0.0001ANCOVA

Secondary/protocol endpoint

Change in Fasting Plasma Glucose (FPG) From Baseline to Week 30

Time frame:Baseline, Week 30

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), mmol/L	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	-3.46	—
Insulin Glargine	-3.27	—
Lixisenatide	-1.5	—

LS Mean Difference-1.9695% CI-2.246 – -1.682p<0.0001Mixed Models Analysis

Secondary/protocol endpoint

Mean Change in 7-point Self-monitored Plasma Glucose (SMPG) Profile From Baseline to Week 30

Time frame:Baseline, Week 30

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mmol/L	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	-3.35	—
Insulin Glargine	-2.66	—
Lixisenatide	-1.95	—

LS Mean Difference-1.495% CI-1.645 – -1.158p<0.0001Mixed Models Analysis

LS Mean Difference-0.6995% CI-0.892 – -0.495p<0.0001Mixed Models Analysis

Secondary/protocol endpoint

Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30

Time frame:Week 30

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), percentage of participants	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	43.2	—
Insulin Glargine	25.1	—
Lixisenatide	27.9	—

Difference in percentage18.0895% CI12.15 – 24.01p<0.0001Cochran-Mantel-Haenszel

Secondary/protocol endpoint

Percentage of Participants Reaching HbA1c <7.0% With No Body Weight Gain at Week 30 and No Documented Symptomatic Hypoglycemia (Plasma Glucose [PG] ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period

Time frame:Baseline up to Week 30

HbA1c <7.0% achievement

threshold achievement, improvement

componentsHbA1c <7.0% achievement, Body weight, absolute change (kg), Documented hypoglycemia

LOINC 4548-4

Posted result

Group	Value (number), percentage of participants	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	31.8	—
Insulin Glargine	18.9	—
Lixisenatide	26.2	—

Difference in percentage12.9895% CI7.5 – 18.45p< 0.0001Cochran-Mantel-Haenszel

Secondary/protocol endpoint

Average Daily Insulin Glargine Dose at Week 30

Time frame:Week 30

descriptive

Posted result

Group	Value (least_squares_mean), Units (U)	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	39.77	—
Insulin Glargine	40.46	—

LS Mean Difference-0.6995% CI-2.632 – 1.252p0.4857Mixed Models Analysis

Secondary/protocol endpoint

Change in 2-Hour Postprandial Plasma Glucose (PPG) From Baseline to Week 30

Time frame:Baseline, Week 30

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mmol/L	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	-5.68	—
Insulin Glargine	-3.31	—
Lixisenatide	-4.58	—

Secondary/protocol endpoint

Percentage of Participants Reaching HbA1c <7.0% at Week 30 With No Documented Symptomatic Hypoglycemia (PG ≤ 70 mg/dL [3.9 mmol/L]) During 30-Week Treatment Period

Time frame:Baseline up to Week 30

HbA1c <7.0% achievement

threshold achievement, improvement

componentsHbA1c <7.0% achievement, Documented hypoglycemia

Posted result

Group	Value (number), percentage of participants	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	53.6	—
Insulin Glargine	44.4	—
Lixisenatide	30.5	—

Secondary/protocol endpoint

Percentage of Participants Requiring Rescue Therapy During 30-Week Treatment Period

Time frame:Baseline up to Week 30

threshold achievement, event

Posted result

Group	Value (number), percentage of participants	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	3.6	—
Insulin Glargine	3.4	—
Lixisenatide	12.4	—

Safety / tolerability / PK

3 endpoints

Secondary/protocol endpoint

Number of Documented Symptomatic Hypoglycemia Events Per Subject-Year

Time frame:First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)

Documented hypoglycemia

event count, event

Posted result

Group	Value (number), Events per subject-year	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	1.44	—
Insulin Glargine	1.22	—
Lixisenatide	0.34	—

Secondary/protocol endpoint

Percentage of Participants With Documented Symptomatic Hypoglycemia

Time frame:First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)

Documented hypoglycemia

threshold achievement, event

Posted result

Group	Value (number), percentage of participants	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	25.6	—
Insulin Glargine	23.6	—
Lixisenatide	6.4	—

Secondary/protocol endpoint

Percentage of Participants With Severe Symptomatic Hypoglycemia

Time frame:First dose of study drug up to 1 day after the last dose administration (median treatment exposure: 211 days)

Severe hypoglycemia

threshold achievement, event

Posted result

Group	Value (number), percentage of participants	95% CI
Insulin Glargine/Lixisenatide Fixed Ratio Combination	0	—
Insulin Glargine	0.2	—
Lixisenatide	0	—

Publications (11)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Efficacy of iGlarLixi on 5-year risk of diabetes-related complications: A simulation study.
Journal of diabetes and its complications2022 Mar (month)PMID35101326doi:10.1016/j.jdiacomp.2022.108132via clinicaltrials gov reference derived + pubmed nct search
Efficacy of iGlarLixi in adults with type 2 diabetes inadequately controlled (glycated haemoglobin ≥8%, ≥64 mmol/mol) on two oral antidiabetes drugs: Post hoc analysis of the LixiLan-O randomized trial.
Diabetes, obesity & metabolism2022 Jan (month)PMID34617398doi:10.1111/dom.14543via pubmed nct search
Glycaemic target attainment in people with Type 2 diabetes treated with insulin glargine/lixisenatide fixed-ratio combination: a post hoc analysis of the LixiLan-O and LixiLan-L trials.
Diabetic medicine : a journal of the British Diabetic Association2020 Feb (month)PMID31365765doi:10.1111/dme.14094via pubmed nct search
EFFICACY AND SAFETY OF IGLARLIXI IN HISPANICS AND NON-HISPANIC WHITES WITH TYPE 2 DIABETES.
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists2019 Nov (month)PMID31241362doi:10.4158/EP-2018-0615via pubmed nct search
Glycaemic benefit of iGlarLixi in insulin-naive type 2 diabetes patients with high HbA1c or those with inadequate glycaemic control on two oral antihyperglycaemic drugs in the LixiLan-O randomized trial.
Diabetes, obesity & metabolism2019 Aug (month)PMID31124299doi:10.1111/dom.13791via clinicaltrials gov reference derived + pubmed nct search
Impact of dose capping in insulin glargine/lixisenatide fixed-ratio combination trials in patients with type 2 diabetes.
Current medical research and opinion2019 Jun (month)PMID30550345doi:10.1080/03007995.2018.1558852via clinicaltrials gov reference derived + pubmed nct search
Post hoc efficacy and safety analysis of insulin glargine/lixisenatide fixed- ratio combination in North American patients compared with the rest of world.
BMJ open diabetes research & care2019 (year)PMID31114694doi:10.1136/bmjdrc-2018-000581via clinicaltrials gov reference derived + pubmed nct search
Propensity-score-matched comparative analyses of simultaneously administered fixed-ratio insulin glargine 100 U and lixisenatide (iGlarLixi) vs sequential administration of insulin glargine and lixisenatide in uncontrolled type 2 diabetes.
Diabetes, obesity & metabolism2018 Dec (month)PMID29974618doi:10.1111/dom.13462via clinicaltrials gov reference derived + pubmed nct search
Low incidence of gastrointestinal adverse events over time with a fixed-ratio combination of insulin glargine and lixisenatide versus lixisenatide alone.
Diabetes, obesity & metabolism2018 Nov (month)PMID29923298doi:10.1111/dom.13444via clinicaltrials gov reference derived + pubmed nct search
Impact of baseline glycated haemoglobin, diabetes duration and body mass index on clinical outcomes in the LixiLan-O trial testing a titratable fixed-ratio combination of insulin glargine/lixisenatide (iGlarLixi) vs insulin glargine and lixisenatide monocomponents.
Diabetes, obesity & metabolism2017 Dec (month)PMID28432746doi:10.1111/dom.12980via clinicaltrials gov reference derived + pubmed nct search
Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial.
Diabetes care2016 Nov (month)PMID27527848doi:10.2337/dc16-0917via CT.gov reference + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.