CompletedPhase 4Results posted

Adding Liraglutide to High Dose Insulin: Breaking the Cycle

Lead sponsor

Ildiko Lingvay

Asset

Liraglutide

Subcutaneous · GLP-1 agonist

Listed sites

Recruiting sites

Actual enrollment

Study population

Obesity / overweight, Type 2 diabetes

Eligibility highlights

•HbA1c 7.5-11%

Primary endpoint

•HbA1c, change

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT01505673

Org study IDIIS-000235

Timeline

Milestones

Study first posted2012-01-06estimated

Results first posted2017-12-15actual

Last update posted2018-01-16actual

Study start2012-01 (month precision)

Primary completion2016-06actual (month precision)

Study completion2016-06actual (month precision)

Assets

Investigational agents

Liraglutide

Who this study enrolls

Obesity / overweightType 2 diabetes

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Type 2 diabetes mellitus

•Insulin dose of >1.8 units/kg/day (represents total daily insulin dose, regardless of formulation, regimen, number of daily shots)

•HbA1c ≥ 7.5% and ≤ 11%

•Age ≥ 18

•Stable comorbidities on stable treatment regimens

•Stable dose of all oral hypoglycemics for ≥ 3 months prior to enrollment

•Ability to provide informed consent before any trial-related activities

Exclusion criteria

•Type 1 diabetes mellitus

•Any contraindication to the MRI procedure (metallic implants, severe claustrophobia, pregnancy, unable to lie still on a hard table for the duration of the procedure, weight above 400 lb - limit of the MRI table, magnet's inner circumference smaller than the largest body circumference)

•History of any pancreatic disease as it might interfere with the pancreatic TG measurement (i.e. pancreatitis, tumors, cysts, type 1 diabetes, any pancreatic surgery)

•End Stage Renal Disease on dialysis due to increased risk of hypoglycemia, and possible interference with accurate measurement of HbA1c

•Incretin therapy (any GLP-1 agonist or DPP-IV inhibitor)

•Unstable or decompensated comorbidities

•Personal or family history of medullary thyroid carcinoma or MEN-2 syndrome

•Severe gastroparesis

•Pregnancy, breast feeding, intention to become pregnant, or not using adequate contraceptive measures

•Organ transplant recipient or waiting list candidate

•Steroid use (current or potential use during the trial)

•Known/suspected allergy to trial medication, excipients, or related products

•Contraindications to study medications, worded specifically as stated in the product's prescribing information

•Non-English speaking volunteers since no interpreters are available and the safety of the volunteers could be jeopardized if adequate and reliable communication is not possible.

Endpoints (54)

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

Patient-reported / QoL

Glycemic / diabetes

MASH / liver

Cardiometabolic biomarkers

Safety / tolerability / PK

Weight & body composition

Other (unclassified)

Weight & body composition

2 endpoints

Secondary/registry result

Weight

Time frame:6-months

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Mean · Kilograms	95% CI
Liraglutide	114	-
Saline Injection	117	-

Secondary/protocol endpoint

Weight

Time frame:6-months

descriptive, improvement

Glycemic / diabetes

17 endpoints

Primary/registry result

Glycemic Control Measured by HbA1c

Time frame:6-months

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Mean · Percent HbA1c	95% CI
Liraglutide	7.9	-
Saline Injection	8.9	-

Primary/protocol endpoint

Glycemic Control Measured by HbA1c

Time frame:6-months

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Beta-Cell Function

Time frame:6-months

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Mean · mg/dL	95% CI
Liraglutide	179	-
Saline Injection	197	-

Secondary/registry result

Glucagon

Time frame:6-months

glucagon auc mixed meal

change from baseline, improvement

Posted result

Group	Mean · pg/mL	95% CI
Liraglutide	107.3	-
Saline Injection	93.8	-

Secondary/registry result

Total Daily Insulin Dose

Time frame:6-months

descriptive

Posted result

Group	Median · IU	95% CI
Liraglutide	200	163 - 275
Saline Injection	218	160 - 260

Secondary/registry result

Beta-Cell Function

Time frame:6 months

change from baseline, improvement

Posted result

Group	Mean · microgram/L	95% CI
Liraglutide	2.48	-
Saline Injection	1.75	-

Secondary/registry result

Matsuda Index as a Measure of Beta Cell Function

Time frame:6 months

descriptive, improvement

Posted result

Group	Mean · index	95% CI
Liraglutide	2.88	1.67 - 3.70
Saline Injection	3.12	1.78 - 9.70

Secondary/registry result

Beta-cell Function

Time frame:6 Months

C-peptide AUC

concentration, improvement

Posted result

Group	Mean · ug/(L/min)	95% CI
Liraglutide	1234.6	-
Saline Injection	922.9	-

Secondary/registry result

Ratio (AUC C-peptide/AUC Glucose)

Time frame:6 months

C-peptide AUC

ratio, improvement

Posted result

Group	Mean · Ratio	95% CI
Liraglutide	0.019	-
Saline Injection	0.013	-

Secondary/registry result/low confidence

AUC Glucose

Time frame:6 months

descriptive, improvement

Posted result

Group	Mean · mg/(dL/min)	95% CI
Liraglutide	71747	-
Saline Injection	79278	-

Secondary/protocol endpoint

Beta-Cell Function

Time frame:6-months

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Total Daily Insulin Dose

Time frame:6-months

change from baseline, improvement

Secondary/protocol endpoint

Beta-Cell Function

Time frame:6 months

change from baseline, improvement

Secondary/protocol endpoint

Matsuda Index as a Measure of Beta Cell Function

Time frame:6 months

descriptive, improvement

Secondary/protocol endpoint

Beta-cell Function

Time frame:6 Months

C-peptide AUC

change from baseline, improvement

Secondary/protocol endpoint

Ratio (AUC C-peptide/AUC Glucose)

Time frame:6 months

C-peptide AUC

ratio, improvement

Secondary/protocol endpoint

AUC Glucose

Time frame:6 months

descriptive, improvement

MASH / liver

4 endpoints

Secondary/registry result/low confidence

Pancreatic and Hepatic Triglyceride Content

Time frame:6-months

Liver fat content, change

change from baseline, improvement

componentsLiver fat content, change, pancreatic triglyceride content change

Posted result

Group	Mean · Percent Triglyceride	95% CI
LiraglutideLiver Triglyceride	12.3	-
Pancreatic Triglyceride	12.53	-
Saline InjectionLiver Triglyceride	12.2	-
Pancreatic Triglyceride	14.64	-

Secondary/registry result/low confidence

Liver Function Blood Test

Time frame:6-months

change from baseline, improvement

Posted result

Group	Mean · U/L	95% CI
LiraglutideALT	25.8	-
AST	26.4	-
Saline InjectionALT	36.0	-
AST	32.1	-

Secondary/protocol endpoint/low confidence

Pancreatic and Hepatic Triglyceride Content

Time frame:6-months

Liver fat content, change

change from baseline, improvement

componentsLiver fat content, change, other pancreatic triglyceride content

Secondary/protocol endpoint/low confidence

Liver Function Blood Test

Time frame:6-months

change from baseline, improvement

Cardiometabolic biomarkers

4 endpoints

Secondary/registry result

Blood Pressure

Time frame:6-months

change from baseline, improvement

Posted result

Group	Mean · mmHg	95% CI
LiraglutideSystolic	134	-
Diastolic	80.5	-
Saline InjectionSystolic	135	-
Diastolic	74.3	-

Secondary/registry result/low confidence

Lipid Profile

Time frame:6-months

descriptive

Posted result

Group	Mean · mg/dL	95% CI
LiraglutideTotal cholesterol	154	-
LDL	83.9	-
HDL	36.6	-
Saline InjectionTotal cholesterol	152	-
LDL	76.3	-
HDL	37.6	-

Secondary/protocol endpoint

Blood Pressure

Time frame:6-months

change from baseline, improvement

Secondary/protocol endpoint

Lipid Profile

Time frame:6-months

descriptive, improvement

Patient-reported / QoL

22 endpoints

Secondary/registry result

Quality of Life Survey (QoL) - General Health Perception

Time frame:6-months

change from baseline, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	3.1	-
Saline Injection	3.6	-

Secondary/registry result

Quality of Life Survey (QoL) - Current Health Perception

Time frame:6 months

descriptive, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	2.1	-
Saline Injection	2.6	-

Secondary/registry result

Quality of Life Survey (QoL) - Treatment Satisfaction

Time frame:6 months

change from baseline, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	2.4	-
Saline Injection	2.7	-

Secondary/registry result

Quality of Life Survey (QoL) - Treatment Impact

Time frame:6 months

change from baseline, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	2.3	-
Saline Injection	2.6	-

Secondary/registry result

Quality of Life Survey (QoL) - Social or Vocational Worry

Time frame:6 months

change from baseline, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	1.5	-
Saline Injection	1.0	-

Secondary/registry result

Quality of Life Survey (QoL) - Hypoglycemia Fear

Time frame:6 months

change from baseline, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	1.9	-
Saline Injection	2.0	-

Secondary/registry result

Quality of Life Survey (QoL) - Glycemia Control Perception

Time frame:6 months

change from baseline, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	2.0	-
Saline Injection	2.9	-

Secondary/registry result

Quality of Life Survey (QoL) - Lifestyle Flexibility

Time frame:6 months

change from baseline, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	2.2	-
Saline Injection	2.6	-

Secondary/registry result

Quality of Life Survey (QoL) - Social Stigma

Time frame:6 months

descriptive, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	2.5	-
Saline Injection	2.4	-

Secondary/registry result

Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment

Time frame:6 months

change from baseline, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	1.6	-
Saline Injection	2.3	-

Secondary/registry result

Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment

Time frame:6 months

PGI, change

change from baseline, improvement

Posted result

Group	Mean · score on a scale	95% CI
Liraglutide	1.0	-
Saline Injection	2.1	-

Secondary/protocol endpoint

Quality of Life Survey (QoL) - General Health Perception

Time frame:6-months

PGI, change

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Current Health Perception

Time frame:6 months

PGI, change

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Treatment Satisfaction

Time frame:6 months

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Treatment Impact

Time frame:6 months

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Social or Vocational Worry

Time frame:6 months

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Hypoglycemia Fear

Time frame:6 months

PGI, change

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Glycemia Control Perception

Time frame:6 months

PGI, change

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Lifestyle Flexibility

Time frame:6 months

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Social Stigma

Time frame:6 months

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment

Time frame:6 months

change from baseline, improvement

Secondary/protocol endpoint

Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment

Time frame:6 months

PGI, change

change from baseline, improvement

Safety / tolerability / PK

3 endpoints

Secondary/registry result

Number of Daily Injections

Time frame:6-months

change from baseline, improvement

Posted result

Group	Mean · number/day	95% CI
Liraglutide	3.7	-
Saline Injection	3.8	-

Secondary/registry result

Hypoglycemic Events

Time frame:6-months

Documented hypoglycemia

event count, event

Posted result

Group	Median · events per month per patient	95% CI
Liraglutide	1.1	0.7 - 1.7
Saline Injection	0.7	0.5 - 1.2

Secondary/protocol endpoint

Hypoglycemic Events

Time frame:6-months

Documented hypoglycemia

event count, event

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

Glucagon

Time frame:6-months

descriptive

Secondary/protocol endpoint/low confidence

Number of Daily Injections

Time frame:6-months

descriptive

Publications (2)

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

Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial.
JAMA internal medicine2016 Jul 1PMID27273731doi:10.1001/jamainternmed.2016.1540via clinicaltrials gov reference derived + pubmed nct search
Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin.
The Journal of clinical endocrinology and metabolism2016 Apr (month)PMID26909799doi:10.1210/jc.2015-3906via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 6, 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 6, 2026 snapshot.