A Study of LY2409021 in Participants With Type 2 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02111096
• Collaborator: (none)
• Enrollment: 174
• Locations: 33
• Arms: 3
• Duration (Months): 17
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The intent of this study is to assess the safety of LY2409021 in participants with Type 2 diabetes mellitus taking metformin and sulfonylurea as prescribed by their personal physician. The study treatment is expected to last 12 months (52 weeks).

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: LY2409021; Drug: Sitagliptin; Drug: Placebo; Drug: Metformin; Drug: Sulfonylurea	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 174 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Phase 2, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety and Efficacy of LY2409021 Compared to Sitagliptin in Subjects With Type 2 Diabetes Mellitus
• Study Start Date: Apr 1, 2014
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2409021 20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Drug: LY2409021; Administered orally; Drug: Metformin; Administered orally; Drug: Sulfonylurea; Administered orally
Active Comparator: Sitagliptin 100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Drug: Sitagliptin; Administered orally; Drug: Metformin; Administered orally; Drug: Sulfonylurea; Administered orally
Placebo Comparator: Placebo Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Drug: Placebo; Administered orally; Drug: Metformin; Administered orally; Drug: Sulfonylurea; Administered orally

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to 6 Months in Hepatic Fat Fraction [Baseline, 6 months]

   The hepatic fat fraction (HFF) was calculated by a core imaging laboratory from noncontrast magnetic resonance imaging (MRI) of the liver. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

Secondary Outcome Measures

1. Change From Baseline to 6 Months in Alanine Aminotransferase Levels [Baseline, 6 months]

   Alanine aminotransferase (ALT) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

2. Number of Participants With Hepatobiliary Adverse Events of Special Interest (AESI) [Baseline, 6 months]

   Number of participants with ALT or AST greater than 3 times the upper limit of normal at a post-baseline visit. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

3. Change From Baseline to 6 Months in Fasting Lipids Levels [Baseline, 6 months]

   Lipid values (cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

4. Change From Baseline to 6 Months in Fasting Blood Glucagon [Baseline, 6 months]

   Glucagon values assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

5. Change From Baseline to 6 Months in Body Weight [Baseline, 6 months]

   Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

6. Change From Baseline to 6 Months in Hemoglobin A1c (HbA1c) [Baseline, 6 months]

   HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, visit, baseline score, and treatment-by-visit.

7. Change From Baseline to 6 Months in Fasting Plasma Glucose [Baseline, 6 months]

   Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

8. Change From Baseline to 6 Months in Blood Pressure [Baseline, 6 months]

   Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured in triplicate throughout the study. At each visit, all available blood pressure measurements for a subject were averaged to provide the blood pressure for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

9. Change From Baseline to 6 Months in Pulse Rate [Baseline, 6 months]

   Seated pulse rate was measured in triplicate throughout the study. At each visit, all available pulse measurements for a subject were averaged to provide the pulse for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.

10. Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG) [Baseline, 6 months]

    7-point profile consists of pre-meal and 2-hour postprandial SMBG measurements for the morning, midday, and evening meals in 1 day and at 3 AM (nocturnal blood glucose measurement). Pre-meal measurements were taken before the subject began eating the meal. Participants recorded their glucose measurements in their study diaries.

11. Population Pharmacokinetics: Apparent Clearance of LY2409021 [Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,]

    Reported as a Population Estimate with % Standard Errors of Estimation (SEE), 5th-95th confidence interval.

12. Population Pharmacokinetics: Apparent Volume of Distribution of LY2409021 [Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,]

13. Rate of Hypoglycemic Events Adjusted Per 30 Days [Baseline through 6 months]

    Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <=70 mg/dL (<=39 mmol/L),is presented. Rate: (30 days) is calculated as: (number of episodes during the time period divided by the number of days during the time period) multiplied by 30.

14. Number of Participants With Hypoglycemic Events [Baseline through 6 months]

    Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <=70 mg/dL (<=39 mmol/L), is presented. The number of subjects with an event are subjects who had at least one episode of documented symptomatic hypoglycemia during the time period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have been treated with a stable dose of metformin for at least 3 months and have been treated with an optimally effective and stable dose of an sulfonylurea for at least 6 months prior to screening.

• HbA1c value between 7.0% and 10.0%, inclusive.

• Body mass index (BMI) between 20 and 45 kilograms/square meter (kg/m^2), inclusive.

Exclusion Criteria:

• Known type 1 diabetes mellitus.

• More than 1 episode of severe hypoglycemia within 6 months prior to screening.

• Two or more emergency room visits or hospitalizations due to poor glucose control in the 6 months prior to screening.

• Severe gastrointestinal disease that may significantly impact gastric emptying or motility or having undergone gastric bypass or gastric banding surgery.

• Previous history or active diagnosis of pancreatitis.

• Positive hepatitis B surface antigen or hepatitis C antibody.

• Clinical signs or symptoms of liver disease, or hepatic aminotransferases (aminotransferase or alanine aminotransferase) greater than 2.0× upper limit of normal (ULN) or elevated alkaline phosphatase (greater than ULN) unrelated to bone metabolic disease.

• Elevated total bilirubin level (greater than ULN), clinically suspicious signs/symptoms of cirrhosis or history of cirrhosis.

• Current diagnosis, personal history of neuroendocrine tumors, family history of any type of multiple endocrine neoplasia (MEN), or Von Hippel-Lindau.

• Contraindications for magnetic resonance imaging.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	John Muir Health Network - The Osteoporosis Center	Concord	California	United States	94520
2	Valley Endocrine, Fresno	Fresno	California	United States	93720
3	National Research Institute	Los Angeles	California	United States	90057
4	Suncoast Research Group, LLC	Miami	Florida	United States	33135
5	New Horizon Research Center	Miami	Florida	United States	33175
6	Clinical Research of West Florida, Inc.	Tampa	Florida	United States	33603
7	University of Hawaii	Honolulu	Hawaii	United States	96813
8	East West Medical Institute	Honolulu	Hawaii	United States	96814
9	Rocky Mountain Diabetes and Osteoporosis Center	Idaho Falls	Idaho	United States	83404
10	Cedar-Crosse Research Center	Chicago	Illinois	United States	60607
11	Midwest CRC	Crystal Lake	Illinois	United States	60012
12	Iderc, P.L.C.	Des Moines	Iowa	United States	50314
13	Cotton O'Neil Clinic	Topeka	Kansas	United States	66606
14	Centex Studies, Inc	Lake Charles	Louisiana	United States	70601
15	Cosmopolitan International Diabetes Center	Columbia	Missouri	United States	65212
16	Mercy Medical Research Institute	Springfield	Missouri	United States	65807
17	Palm Research Center	Las Vegas	Nevada	United States	89148
18	SHS Clinical Research Group	Toms River	New Jersey	United States	08753
19	Office:Alwine,Lk	Downingtown	Pennsylvania	United States	19335
20	University Diabetes and Endocrine Consultants	Chattanooga	Tennessee	United States	37411
21	Dallas Diabetes Endocrine Center	Dallas	Texas	United States	75230
22	Galenos Research	Dallas	Texas	United States	75251
23	San Gabriel Clinical Research	Georgetown	Texas	United States	78626
24	Oakwell Clinical Research	San Antonio	Texas	United States	78218
25	Victorium Clinical Research	San Antonio	Texas	United States	78240
26	Polyclinic	Seattle	Washington	United States	98104
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Athens		Greece	11527
28	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Thessaloniki		Greece	54636
29	PRADNET, Inc. Centro Especializado de Nutricion y Bariatria	Hato Rey		Puerto Rico	00917
30	American Telemedicine Center	San Juan		Puerto Rico	00917-3104
31	GCM Medical Group PSC	San Juan		Puerto Rico	909
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Changhua		Taiwan	500
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Yong Kung City		Taiwan	71004

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02111096
• Other Study ID Numbers: 15286; I1R-MC-GLDJ; 2013-004275-12
• First Posted: Apr 10, 2014
• Last Update Posted: Oct 9, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Sitagliptin Phosphate

Study Results

Participant Flow

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Period Title: Overall Study
STARTED	65	41	68
Received at Least 1 Dose of Study Drug	65	41	68
COMPLETED	1	0	2
NOT COMPLETED	64	41	66

Baseline Characteristics

Arm/Group Title	LY2409021	Sitagliptin	Placebo	Total
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Total of all reporting groups
Overall Participants	65	41	68	174
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.9 (8.33)	57.1 (8.99)	57.8 (8.21)	57.3 (8.41)
Sex: Female, Male (Count of Participants)
Female	24 36.9%	10 24.4%	31 45.6%	65 37.4%
Male	41 63.1%	31 75.6%	37 54.4%	109 62.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	30 46.2%	19 46.3%	42 61.8%	91 52.3%
Not Hispanic or Latino	34 52.3%	21 51.2%	25 36.8%	80 46%
Unknown or Not Reported	1 1.5%	1 2.4%	1 1.5%	3 1.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	4 6.2%	2 4.9%	5 7.4%	11 6.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	14 21.5%	6 14.6%	11 16.2%	31 17.8%
White	42 64.6%	31 75.6%	51 75%	124 71.3%
More than one race	5 7.7%	2 4.9%	1 1.5%	8 4.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Greece	6 9.2%	4 9.8%	6 8.8%	16 9.2%
Puerto Rico	8 12.3%	5 12.2%	13 19.1%	26 14.9%
United States	48 73.8%	31 75.6%	45 66.2%	124 71.3%
Taiwan	3 4.6%	1 2.4%	4 5.9%	8 4.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to 6 Months in Hepatic Fat Fraction
Description	The hepatic fat fraction (HFF) was calculated by a core imaging laboratory from noncontrast magnetic resonance imaging (MRI) of the liver. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, have usable MRI HFF data at baseline and at least 1 post-baseline time point, excluding any data collected after stopping study drug.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	62	39	67
Least Squares Mean (95% Confidence Interval) [percentage]	3.65	-0.07	-0.79

2. Secondary Outcome

Title	Change From Baseline to 6 Months in Alanine Aminotransferase Levels
Description	Alanine aminotransferase (ALT) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, baseline data and at least 1 post-baseline time point.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	64	39	67
Least Squares Mean (95% Confidence Interval) [microgram per Liter (µ/L)]	9.4	2.6	-1.3

3. Secondary Outcome

Title	Number of Participants With Hepatobiliary Adverse Events of Special Interest (AESI)
Description	Number of participants with ALT or AST greater than 3 times the upper limit of normal at a post-baseline visit. A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	65	41	68
Count of Participants [Participants]	0 0%	1 2.4%	1 1.5%

4. Secondary Outcome

Title	Change From Baseline to 6 Months in Fasting Lipids Levels
Description	Lipid values (cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides) assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of randomized study drug, have data at baseline and at least 1 post-baseline time point.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	65	41	68
Cholesterol	0.468	0.006	0.130
HDL Cholesterol	0.046	0.032	-0.021
Triglycerides	0.375	0.078	0.099
LDL cholesterol	0.244	-0.075	0.019

5. Secondary Outcome

Title	Change From Baseline to 6 Months in Fasting Blood Glucagon
Description	Glucagon values assessed by a central laboratory. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, have data at baseline and at least 1 post-baseline time point.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	57	38	61
Least Squares Mean (95% Confidence Interval) [picomol per liter (pmol/L)]	44.06	3.38	5.05

6. Secondary Outcome

Title	Change From Baseline to 6 Months in Body Weight
Description	Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, have data at baseline and at least 1 post-baseline time point.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	64	40	68
Least Squares Mean (90% Confidence Interval) [kilograms (kg)]	0.37	-0.08	-0.05

7. Secondary Outcome

Title	Change From Baseline to 6 Months in Hemoglobin A1c (HbA1c)
Description	HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, visit, baseline score, and treatment-by-visit.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, have data at baseline and at least 1 post-baseline time point, excluding data collected after stopping study drug and/or starting rescue therapy.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	63	40	68
Least Squares Mean (95% Confidence Interval) [percent of HbA1c]	-0.63	-0.42	0.14

8. Secondary Outcome

Title	Change From Baseline to 6 Months in Fasting Plasma Glucose
Description	Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug,have data at baseline and at least 1 post-baseline time point, excluding data collected after stopping study drug and/or starting rescue therapy.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	63	40	61
Least Squares Mean (95% Confidence Interval) [milligram per decililiter (mg/dL)]	-20.5	-9.4	6.6

9. Secondary Outcome

Title	Change From Baseline to 6 Months in Blood Pressure
Description	Seated systolic blood pressure (SBP) and seated diastolic blood pressure (DBP) were measured in triplicate throughout the study. At each visit, all available blood pressure measurements for a subject were averaged to provide the blood pressure for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, have data at baseline and at least 1 post-baseline time point.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	63	40	68
Systolic Blood Pressure	6.1	1.1	1.8
Diastolic Blood Pressure	2.9	0.3	1.5

10. Secondary Outcome

Title	Change From Baseline to 6 Months in Pulse Rate
Description	Seated pulse rate was measured in triplicate throughout the study. At each visit, all available pulse measurements for a subject were averaged to provide the pulse for that visit. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, country, baseline HbA1c stratum (<=8.0%, >8.0%), visit, baseline score, and treatment-by-visit.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, have data at baseline and at least 1 post-baseline time point.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	63	40	68
Least Squares Mean (95% Confidence Interval) [beats per minutes (bpm)]	1.5	3.5	1.2

11. Secondary Outcome

Title	Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG)
Description	7-point profile consists of pre-meal and 2-hour postprandial SMBG measurements for the morning, midday, and evening meals in 1 day and at 3 AM (nocturnal blood glucose measurement). Pre-meal measurements were taken before the subject began eating the meal. Participants recorded their glucose measurements in their study diaries.
Time Frame	Baseline, 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, have data at baseline and at least 1 post-baseline time point, excluding data collected after stopping study drug and/or starting rescue therapy.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	65	41	68
Morning Pre-Meal	-29.4 (40.36)	-8.13 (31.25)	-4.31 (26.69)
Mid-day Pre Meal	-28.43 (41.13)	-30.58 (48.98)	-9.30 (51.08)
Morning 2 Hour (Hr) Post Meal	-38.8 (47.71)	-30.76 (44.35)	-18.28 (46.20)
Midday 2 hr Post Meal	-24.22 (52.64)	-25.20 (61.57)	-10.49 (54.17)
Evening Pre Meal	-24.58 (50.78)	-16.78 (51.09)	-14.13 (50.01)
Evening 2 hr Post Meal	-28.36 (58.92)	-21.12 (48.19)	-9.50 (48.62)
Three AM	-22.78 (42.49)	-20.12 (57.39)	0.88 (41.94)

12. Secondary Outcome

Title	Population Pharmacokinetics: Apparent Clearance of LY2409021
Description	Reported as a Population Estimate with % Standard Errors of Estimation (SEE), 5th-95th confidence interval.
Time Frame	Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable PK data.

Arm/Group Title	LY2409021
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	65
Number (95% Confidence Interval) [Liters per hour (L/h)]	0.526

13. Secondary Outcome

Title	Population Pharmacokinetics: Apparent Volume of Distribution of LY2409021
Time Frame	Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had evaluable PK data.

Arm/Group Title	LY2409021
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	65
Number (95% Confidence Interval) [Liters (L)]	31.9

14. Secondary Outcome

Title	Rate of Hypoglycemic Events Adjusted Per 30 Days
Description	Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <=70 mg/dL (<=39 mmol/L),is presented. Rate: (30 days) is calculated as: (number of episodes during the time period divided by the number of days during the time period) multiplied by 30.
Time Frame	Baseline through 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, have data at baseline and at least 1 post-baseline time point, excluding data collected after stopping study drug and/or starting rescue therapy.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remained on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	64	40	68
Number [number of episodes per day]	0.27	0.19	0.12

15. Secondary Outcome

Title	Number of Participants With Hypoglycemic Events
Description	Documented symptomatic hypoglycemia, an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration <=70 mg/dL (<=39 mmol/L), is presented. The number of subjects with an event are subjects who had at least one episode of documented symptomatic hypoglycemia during the time period.
Time Frame	Baseline through 6 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug, have data at baseline and at least 1 post-baseline time point, excluding data collected after study drug and/or starting rescue therapy.

Arm/Group Title	LY2409021	Sitagliptin	Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.	Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
Measure Participants	64	40	68
Count of Participants [Participants]	20 30.8%	40 97.6%	68 100%

Adverse Events

Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study drug.
Arm/Group Title	LY2409021		Sitagliptin		Placebo
Arm/Group Description	20 milligrams (mg) LY2409021 given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.		100 mg sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.		Placebo matching LY2409021 and sitagliptin given orally once daily in the morning for 12 months (52 weeks). Participants remain on stable doses of metformin and sulfonylurea, as prescribed by their personal physician.
All Cause Mortality
	LY2409021		Sitagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2409021		Sitagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/65 (7.7%)		5/41 (12.2%)		1/68 (1.5%)
Cardiac disorders
Acute coronary syndrome	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Atrial fibrillation	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Cardiac failure congestive	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Ventricular extrasystoles	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Gastrointestinal disorders
Small intestinal obstruction	0/65 (0%)	0	0/41 (0%)	0	1/68 (1.5%)	1
Infections and infestations
Abscess limb	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Device related infection	1/65 (1.5%)	1	0/41 (0%)	0	0/68 (0%)	0
Gastroenteritis	1/65 (1.5%)	1	0/41 (0%)	0	0/68 (0%)	0
Infectious colitis	1/65 (1.5%)	1	0/41 (0%)	0	0/68 (0%)	0
Pneumonia	1/65 (1.5%)	1	0/41 (0%)	0	0/68 (0%)	0
Injury, poisoning and procedural complications
Femur fracture	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Joint dislocation	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma	1/65 (1.5%)	1	0/41 (0%)	0	0/68 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/65 (1.5%)	2	0/41 (0%)	0	0/68 (0%)	0
Vascular disorders
Hypertensive crisis	1/65 (1.5%)	1	0/41 (0%)	0	0/68 (0%)	0
Malignant hypertension	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Other (Not Including Serious) Adverse Events
	LY2409021		Sitagliptin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/65 (40%)		22/41 (53.7%)		21/68 (30.9%)
Blood and lymphatic system disorders
Anaemia	1/65 (1.5%)	1	1/41 (2.4%)	1	0/68 (0%)	0
Cardiac disorders
Coronary artery disease	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Sinus bradycardia	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Ventricular extrasystoles	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Congenital, familial and genetic disorders
Type v hyperlipidaemia	1/65 (1.5%)	1	0/41 (0%)	0	2/68 (2.9%)	2
Ear and labyrinth disorders
Cerumen impaction	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Eye disorders
Blindness unilateral	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Diabetic retinal oedema	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Eye swelling	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Glaucoma	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/65 (1.5%)	1	1/41 (2.4%)	1	1/68 (1.5%)	1
Constipation	2/65 (3.1%)	2	3/41 (7.3%)	3	0/68 (0%)	0
Diarrhoea	3/65 (4.6%)	3	1/41 (2.4%)	1	3/68 (4.4%)	5
Dry mouth	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Toothache	1/65 (1.5%)	1	0/41 (0%)	0	2/68 (2.9%)	2
General disorders
Chest pain	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Fatigue	2/65 (3.1%)	2	1/41 (2.4%)	1	0/68 (0%)	0
Oedema peripheral	0/65 (0%)	0	2/41 (4.9%)	3	0/68 (0%)	0
Pain	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Polyp	0/65 (0%)	0	0/41 (0%)	0	2/68 (2.9%)	2
Pyrexia	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Hepatobiliary disorders
Hepatic cyst	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Immune system disorders
Allergy to vaccine	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Seasonal allergy	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Infections and infestations
Bronchitis	1/65 (1.5%)	1	3/41 (7.3%)	3	0/68 (0%)	0
Conjunctivitis	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Influenza	2/65 (3.1%)	2	2/41 (4.9%)	2	1/68 (1.5%)	1
Labyrinthitis	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Nasopharyngitis	2/65 (3.1%)	3	2/41 (4.9%)	3	1/68 (1.5%)	1
Pharyngitis	1/65 (1.5%)	1	1/41 (2.4%)	1	1/68 (1.5%)	1
Pharyngitis streptococcal	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Sinusitis	2/65 (3.1%)	2	0/41 (0%)	0	1/68 (1.5%)	1
Subcutaneous abscess	0/65 (0%)	0	1/41 (2.4%)	1	1/68 (1.5%)	1
Upper respiratory tract infection	4/65 (6.2%)	6	3/41 (7.3%)	3	3/68 (4.4%)	4
Viral infection	2/65 (3.1%)	4	0/41 (0%)	0	0/68 (0%)	0
Vulvovaginal candidiasis	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Investigations
Alanine aminotransferase increased	0/65 (0%)	0	1/41 (2.4%)	1	1/68 (1.5%)	1
Aspartate aminotransferase increased	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Blood pressure diastolic increased	2/65 (3.1%)	2	1/41 (2.4%)	1	0/68 (0%)	0
Free fatty acids increased	2/65 (3.1%)	2	1/41 (2.4%)	1	1/68 (1.5%)	1
Glomerular filtration rate decreased	1/65 (1.5%)	1	1/41 (2.4%)	1	2/68 (2.9%)	2
Heart rate increased	0/65 (0%)	0	2/41 (4.9%)	2	0/68 (0%)	0
Weight decreased	2/65 (3.1%)	2	1/41 (2.4%)	1	0/68 (0%)	0
Weight increased	1/65 (1.5%)	1	1/41 (2.4%)	1	1/68 (1.5%)	1
Metabolism and nutrition disorders
Abnormal weight gain	2/65 (3.1%)	2	0/41 (0%)	0	0/68 (0%)	0
Hyperglycaemia	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/65 (3.1%)	2	0/41 (0%)	0	1/68 (1.5%)	2
Arthritis	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Back pain	1/65 (1.5%)	1	1/41 (2.4%)	1	1/68 (1.5%)	1
Intervertebral disc degeneration	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Musculoskeletal pain	2/65 (3.1%)	2	1/41 (2.4%)	1	0/68 (0%)	0
Musculoskeletal stiffness	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Myalgia	2/65 (3.1%)	2	2/41 (4.9%)	3	0/68 (0%)	0
Pain in extremity	2/65 (3.1%)	2	1/41 (2.4%)	1	0/68 (0%)	0
Tendonitis	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Colon adenoma	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Nervous system disorders
Carotid arteriosclerosis	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Dizziness	4/65 (6.2%)	5	0/41 (0%)	0	0/68 (0%)	0
Headache	6/65 (9.2%)	8	2/41 (4.9%)	8	1/68 (1.5%)	1
Tension headache	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Psychiatric disorders
Depression	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Renal and urinary disorders
Microalbuminuria	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Nephrolithiasis	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Reproductive system and breast disorders
Atrophic vulvovaginitis	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Rash	0/65 (0%)	0	1/41 (2.4%)	1	0/68 (0%)	0
Vascular disorders
Hypertension	2/65 (3.1%)	2	1/41 (2.4%)	1	3/68 (4.4%)	3

Limitations/Caveats

Terminated, The overall benefit-risk profile did not support continued development of LY2409021 for type 2 diabetes.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.