CompletedPhase 1Results posted

Effect of LY2189265 on Insulin Secretion in Response to Intravenous Glucose

The Effect of LY2189265 on Insulin Secretion in Response to Intravenous Glucose Infusion

Lead sponsor

Eli Lilly and Company

Asset

Dulaglutide

Subcutaneous · GLP-1 agonist

Listed sites

Recruiting sites

Actual enrollment

Study population

Healthy volunteers, Type 2 diabetes

Eligibility highlights

•BMI 19-25•HbA1c 6-9.5%•Healthy volunteers

Primary endpoints

•Maximum Insulin Concentration (Cmax) - First Phase Response•AUC of Insulin (AUC) - First Phase Response•Maximum Insulin Concentration (Cmax) - Second Phase Response

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 IDNCT01300260

Org study ID11371

Secondary IDH9X-MC-GBCIEli Lilly and Company

Timeline

Milestones

Study first posted2011-02-21estimated

Last update posted2014-10-07estimated

Results first posted2014-10-07estimated

Study start2011-02 (month precision)

Primary completion2011-08actual (month precision)

Study completion2011-08actual (month precision)

Assets

Investigational agents

Dulaglutide

Who this study enrolls

Healthy volunteersType 2 diabetes

Who can enroll

Minimum age18 Years

Maximum age65 Years

SexAll

Healthy volunteersAccepted

Inclusion criteria

All Participants

•Women must be surgically sterile (hysterectomy or bilateral oophorectomy or tubal ligation) or postmenopausal as defined by age >45 years without use of oral contraceptive agents for greater than 1 year and have either:

-spontaneous amenorrhea greater than 12 months, or

-spontaneous amenorrhea 6 to 12 months with documented follicle stimulating hormone (FSH) >25 milli international units/milliliter (mIU/mL) and serum estradiol <73 picomoles/liter (pmol/L) (20 picograms/milliliter [pg/mL])

•Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures

•Have given written informed consent approved by Lilly and the ethical review board governing the site

•Have serum creatinine <150 micromoles/liter (µmol/L) (<1.3 milligrams/deciliter [mg/dl] in women, <170 µmol/L [<1.5 mg/dL] in men)

•Have normal hemoglobin result, as determined by the investigator

Healthy Participants

•Overtly healthy men and women as determined by medical history, normal lab results and physical examination.

•Body mass index (BMI) between 19 and 25 kilograms/meter squared (kg/m^2), inclusive.

•Normal blood pressure and heart rate as determined by the investigator

•Have a normal response to an oral glucose tolerance test (OGTT) (glucose <7.8 millimoles/liter [mmol/L] [<140 mg/dL] at 2 hours after 75 grams (g) oral glucose load)

Participants with type 2 diabetes mellitus (T2DM)

•Participants will have a BMI between 22.0 and 40.0 kg/m^2

•Have T2DM controlled with diet and exercise alone or metformin for at least 4 weeks prior to admission

•Have a hemoglobin A1c (HbA1c) value at screening (or within 4 weeks prior to screening) of 6.0% to 9.5%

•Diagnosed with T2DM within the past 10 years

•Clinical laboratory test results within normal range or deemed clinically insignificant by the Investigator. Abnormalities of serum glucose, serum lipids, urinary glucose, and urinary protein consistent with T2DM are acceptable.

•Participants who are taking stable-dose prescription medications (for example, antihypertensive agents, aspirin, lipid-lowering agents) for treatment of concurrent medical conditions are permitted to participate providing the medication is not associated with development of torsade de pointes. However, use of beta-blockers and thiazide diuretics are not permitted during this study.

Exclusion criteria

All Participants

•Within 30 days of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication

•Known allergies to Glucagon-Like Peptide 1 (GLP-1) related compounds

•Have previously completed or withdrawn from this study or any other study in the last year investigating glucagon-like peptides or incretin mimetics including exenatide (Byetta®)

•Regular use of known drugs of abuse and/or positive findings on urinary drug screening, other than findings consistent with medication prescribed by the participant's physician(s)

•History or presence of cardiovascular, respiratory, renal, endocrine (except T2DM), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs or of constituting a risk when taking the study medication or interfering with the interpretation of data

•Have a history or presence of gastrointestinal disorder

•Poorly controlled hypertension (systolic greater than 160 millimeters of mercury [mmHg], diastolic greater than 95 mmHg) and/or evidence of labile blood pressure including symptomatic postural hypotension. Use of beta-blockers or thiazide diuretics is not permitted during the study

•Have a clinically significant history of cardiac disease or presence of active cardiac disease within 1 year of the screening period

•Evidence of hepatitis C and/or positive hepatitis C antibody

•Evidence of hepatitis B and/or positive hepatitis B surface antigen

•Evidence of human immunodeficiency virus (HIV) and/or positive for HIV antibodies

•Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) or are unwilling to follow alcohol restrictions (1 unit = 12 ounces [oz] or 360 milliliters[mL] of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).

•Smoke more than 10 cigarettes or equivalent in nicotine use or nicotine substitutes per day

•Regular use of systemic corticosteroids by oral, intravenous, or intramuscular route, or potent, inhaled, or intranasal steroids known to have a high rate of systemic absorption

•Have a history or presence of significant active neuropsychiatric disease

•Blood donation of more than 500 mL in the last 3 months or any blood donation within the last month

•Any other condition, which in the opinion of the investigator would preclude participation in the study

•An abnormality in the 12-lead electrocardiogram (ECG) that in the opinion of the investigator increases the risk of participating in the study.

•Any clinically significant abnormal hematology, clinical chemistry, or urinary result(s) as determined by the investigator

•Evidence of significant active uncontrolled endocrine or autoimmune abnormalities (for example thyroid disease, or pernicious anemia) as judged by the screening physician

Healthy Participants

•Intended use of over-the-counter or prescription medication 7 and 14 days, respectively, prior to dosing.

Participants with T2DM

•Clinically significant peripheral vascular occlusive disease (PVOD).

•Known severe exudative diabetic retinopathy

•Known significant autonomic neuropathy as evidenced by urinary retention, diabetic diarrhea, or gastroparesis

•Have experienced a ketoacidotic episode (pH less than 7.3) requiring hospitalization in the last 6 months

•Outpatient use of insulin for control of diabetes within the past 2 years

•Use of antidiabetic agents other than metformin in the 4 weeks prior to study entry or use of thiazolidinediones within 12 weeks of study entry

Endpoints (12)

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

Glycemic / diabetes

9 endpoints

Primary/registry result/low confidence

Maximum Insulin Concentration (Cmax) - First Phase Response

Time frame:0-10 minutes after dextrose bolus on Day 3 postdose

concentration, descriptive

Posted result

Group	Geometric mean · picomole per liter (pmol/L)	95% CI
Healthy Participants: Placebo	233	154 - 352
Healthy Participants: LY2189265	689	455 - 1041
Participants With Type 2 Diabetes Mellitus (T2DM): Placebo	74.3	46.8 - 118
Participants With Type 2 Diabetes Mellitus (T2DM): LY2189265	401	252 - 637

Geometric least squares (ls) mean ratio2.9695% CI2.41 - 3.64p<0.001Mixed Models Analysis

Geometric least squares (ls) means ratio5.4095% CI4.09 - 7.13p<0.001Mixed Models Analysis

Primary/registry result

Area Under the Insulin Concentration-time Curve (AUC) - First Phase Response

Time frame:0-10 minutes after dextrose bolus on Day 3 postdose

concentration, descriptive

Posted result

Group	Geometric mean · picomole times hour per liter (pmol*h/L)	95% CI
Healthy Participants: Placebo	22.9	15.0 - 34.9
Healthy Participants: LY2189265	70.7	46.3 - 108
Participants With Type 2 Diabetes Mellitus (T2DM): Placebo	5.06	2.90 - 8.83
Participants With Type 2 Diabetes Mellitus (T2DM): LY2189265	40.1	22.8 - 70.3

Geometric least squares (ls) mean ratio3.0995% CI2.66 - 3.59p<0.001Mixed Models Analysis

Geometric least squares (ls) mean ratio7.9295% CI4.82 - 13.0p<0.001Mixed Models Analysis

Primary/registry result

Insulin Area Under the Curve (AUC) - Second Phase Response

Time frame:10-180 minutes after dextrose bolus on Day 3 post dose

concentration, descriptive

Posted result

Group	Geometric mean · picomole times hour per liter (pmol*h/L)	95% CI
Healthy Participants: Placebo	68.8	41.7 - 114
Healthy Participants: LY2189265	141	85.3 - 232
Participants With Type 2 Diabetes Mellitus (T2DM): Placebo	147	103 - 209
Participants With Type 2 Diabetes Mellitus (T2DM): LY2189265	357	250 - 511

Geometric least squares (ls) mean ratio2.0495% CI1.26 - 3.31p0.011Mixed Models Analysis

Geometric least squares (ls) mean ratio2.4495% CI1.71 - 3.47p<0.001Mixed Models Analysis

Primary/protocol endpoint

Maximum Insulin Concentration (Cmax) - First Phase Response

Time frame:0-10 minutes after dextrose bolus on Day 3 postdose

concentration, descriptive

Primary/protocol endpoint

Area Under the Insulin Concentration-time Curve (AUC) - First Phase Response

Time frame:0-10 minutes after dextrose bolus on Day 3 postdose

concentration, descriptive

Primary/protocol endpoint

Maximum Insulin Concentration (Cmax) - Second Phase Response

Time frame:10-180 minutes after dextrose bolus on Day 3 postdose

concentration, descriptive

Primary/protocol endpoint/low confidence

Insulin Area Under the Curve (AUC) - Second Phase Response

Time frame:10-180 minutes after dextrose bolus on Day 3 post dose

concentration, descriptive

Other/protocol endpoint

Area Under the Insulin Concentration-time Curve (AUC)

Time frame:After glucagon bolus on Day 3 postdose

concentration, descriptive

Other_pre_specified/registry result

Area Under the Insulin Concentration-time Curve (AUC)

Time frame:After glucagon bolus on Day 3 postdose

concentration, descriptive

Posted result

Group	Geometric mean · picomole times hour per liter (pmol*h/L)	95% CI
Healthy Participants: Placebo	239	167 - 340
Healthy Participants: LY2189265	341	239 - 486
Participants With Type 2 Diabetes Mellitus (T2DM): Placebo	236	177 - 316
Participants With Type 2 Diabetes Mellitus (T2DM): LY2189265	414	310 - 554

Geometric least squares (ls) mean ratio1.4395% CI1.14 - 1.80p0.009Mixed Models Analysis

Geometric least squares (ls) mean ratio1.7595% CI1.59 - 1.94p<0.001Mixed Models Analysis

Safety / tolerability / PK

3 endpoints

Primary/registry result

Maximum Insulin Concentration (Cmax) - Second Phase Response

Time frame:10-180 minutes after dextrose bolus on Day 3 postdose

Cmax

concentration, descriptive

Posted result

Group	Geometric mean · picomole per liter (pmol/L)]	95% CI
Healthy Participants: Placebo	89.2	64.7 - 123
Healthy Participants: LY2189265	370	269 - 511
Participants With Type 2 Diabetes Mellitus (T2DM): Placebo	95.9	66.3 - 139
Participants With Type 2 Diabetes Mellitus (T2DM): LY2189265	363	250 - 526

Geometric least squares (ls) mean ratio4.1595% CI3.45 - 5.00p<0.001Mixed Models Analysis

Geometric least squares (ls) mean ratio3.7895% CI2.99 - 4.78p<0.001Mixed Models Analysis

Secondary/registry result

Insulin Maximum Concentration (Cmax)

Time frame:After glucagon bolus on Day 3 postdose

Cmax

concentration, descriptive

Posted result

Group	Geometric mean · picomole per liter (pmol/L)	95% CI
Healthy Participants: Placebo	996	716 - 1386
Healthy Participants: LY2189265	1215	874 - 1690
Participants With Type 2 Diabetes Mellitus (T2DM): Placebo	1088	827 - 1431
Participants With Type 2 Diabetes Mellitus (T2DM): LY2189265	1514	1151 - 1991

Geometric least squares (ls) mean ratio1.2295% CI1.04 - 1.43p0.021Mixed Models Analysis

Geometric least squares (ls) mean ratio1.3995% CI1.27 - 1.53p<0.001Mixed Models Analysis

Secondary/protocol endpoint

Insulin Maximum Concentration (Cmax)

Time frame:After glucagon bolus on Day 3 postdose

Cmax

concentration, descriptive

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.