Trial Outcomes & Findings for A Study of LY2409021 in Participants With Type 2 Diabetes Mellitus (NCT NCT02111096)

Last Updated: 2019-10-09

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

174 participants

Primary outcome timeframe

Baseline, 6 months

Results posted on

2019-10-09

Participant Flow

Participant milestones

Participant milestones
Measure	LY2409021 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.	Sitagliptin 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 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.
Overall Study STARTED	65	41	68
Overall Study Received at Least 1 Dose of Study Drug	65	41	68
Overall Study COMPLETED	1	0	2
Overall Study NOT COMPLETED	64	41	66

Reasons for withdrawal

Reasons for withdrawal
Measure	LY2409021 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.	Sitagliptin 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 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.
Overall Study Adverse Event	4	1	2
Overall Study Non-Compliance with Study Drug	1	1	0
Overall Study Lost to Follow Up	1	1	1
Overall Study Physician Decision	0	1	0
Overall Study Protocol Violation	1	0	1
Overall Study Terminated by Sponsor	53	35	54
Overall Study Withdrawal by Subject	4	2	8

Baseline Characteristics

A Study of LY2409021 in Participants With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LY2409021 n=65 Participants 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.	Sitagliptin n=41 Participants 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 n=68 Participants 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 n=174 Participants Total of all reporting groups
Age, Continuous	56.9 years STANDARD_DEVIATION 8.33 • n=5 Participants	57.1 years STANDARD_DEVIATION 8.99 • n=7 Participants	57.8 years STANDARD_DEVIATION 8.21 • n=5 Participants	57.3 years STANDARD_DEVIATION 8.41 • n=4 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	10 Participants n=7 Participants	31 Participants n=5 Participants	65 Participants n=4 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	31 Participants n=7 Participants	37 Participants n=5 Participants	109 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	30 Participants n=5 Participants	19 Participants n=7 Participants	42 Participants n=5 Participants	91 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=5 Participants	21 Participants n=7 Participants	25 Participants n=5 Participants	80 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	31 Participants n=4 Participants
Race (NIH/OMB) White	42 Participants n=5 Participants	31 Participants n=7 Participants	51 Participants n=5 Participants	124 Participants n=4 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Greece	6 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Region of Enrollment Puerto Rico	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants	26 Participants n=4 Participants
Region of Enrollment United States	48 Participants n=5 Participants	31 Participants n=7 Participants	45 Participants n=5 Participants	124 Participants n=4 Participants
Region of Enrollment Taiwan	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, 6 months

Population: 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.

Outcome measures

Outcome measures
Measure	LY2409021 n=62 Participants 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.	Sitagliptin n=39 Participants 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 n=67 Participants 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.
Change From Baseline to 6 Months in Hepatic Fat Fraction	3.65 percentage Interval 2.13 to 5.17	-0.07 percentage Interval -1.94 to 1.79	-0.79 percentage Interval -2.28 to 0.7

SECONDARY outcome

Timeframe: Baseline, 6 months

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

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.

Outcome measures

Outcome measures
Measure	LY2409021 n=64 Participants 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.	Sitagliptin n=39 Participants 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 n=67 Participants 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.
Change From Baseline to 6 Months in Alanine Aminotransferase Levels	9.4 microgram per Liter (µ/L) Interval 4.6 to 14.2	2.6 microgram per Liter (µ/L) Interval -3.1 to 8.3	-1.3 microgram per Liter (µ/L) Interval -6.0 to 3.4

SECONDARY outcome

Timeframe: Baseline, 6 months

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

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.

Outcome measures

Outcome measures
Measure	LY2409021 n=65 Participants 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.	Sitagliptin n=41 Participants 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 n=68 Participants 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.
Number of Participants With Hepatobiliary Adverse Events of Special Interest (AESI)	0 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, 6 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	LY2409021 n=65 Participants 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.	Sitagliptin n=41 Participants 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 n=68 Participants 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.
Change From Baseline to 6 Months in Fasting Lipids Levels Cholesterol	0.468 millimol per liter (mmol/L) Interval 0.222 to 0.714	0.006 millimol per liter (mmol/L) Interval -0.282 to 0.295	0.130 millimol per liter (mmol/L) Interval -0.11 to 0.371
Change From Baseline to 6 Months in Fasting Lipids Levels HDL Cholesterol	0.046 millimol per liter (mmol/L) Interval -0.008 to 0.1	0.032 millimol per liter (mmol/L) Interval -0.031 to 0.095	-0.021 millimol per liter (mmol/L) Interval -0.032 to 0.074
Change From Baseline to 6 Months in Fasting Lipids Levels Triglycerides	0.375 millimol per liter (mmol/L) Interval 0.087 to 0.644	0.078 millimol per liter (mmol/L) Interval -0.264 to 0.42	0.099 millimol per liter (mmol/L) Interval -0.183 to 0.381
Change From Baseline to 6 Months in Fasting Lipids Levels LDL cholesterol	0.244 millimol per liter (mmol/L) Interval 0.019 to 0.486	-0.075 millimol per liter (mmol/L) Interval -0.342 to 0.192	0.019 millimol per liter (mmol/L) Interval -0.2 to 0.239

SECONDARY outcome

Timeframe: Baseline, 6 months

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

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.

Outcome measures

Outcome measures
Measure	LY2409021 n=57 Participants 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.	Sitagliptin n=38 Participants 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 n=61 Participants 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.
Change From Baseline to 6 Months in Fasting Blood Glucagon	44.06 picomol per liter (pmol/L) Interval 36.36 to 51.76	3.38 picomol per liter (pmol/L) Interval -5.64 to 12.41	5.05 picomol per liter (pmol/L) Interval -2.5 to 12.6

SECONDARY outcome

Timeframe: Baseline, 6 months

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

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.

Outcome measures

Outcome measures
Measure	LY2409021 n=64 Participants 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.	Sitagliptin n=40 Participants 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 n=68 Participants 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.
Change From Baseline to 6 Months in Body Weight	0.37 kilograms (kg) Interval 0.12 to 0.63	-0.08 kilograms (kg) Interval -0.39 to 0.22	-0.05 kilograms (kg) Interval -0.3 to 0.2

SECONDARY outcome

Timeframe: Baseline, 6 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	LY2409021 n=63 Participants 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.	Sitagliptin n=40 Participants 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 n=68 Participants 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.
Change From Baseline to 6 Months in Hemoglobin A1c (HbA1c)	-0.63 percent of HbA1c Interval -0.94 to -0.32	-0.42 percent of HbA1c Interval -0.8 to -0.05	0.14 percent of HbA1c Interval -0.15 to 0.45

SECONDARY outcome

Timeframe: Baseline, 6 months

Population: 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.

Outcome measures

Outcome measures
Measure	LY2409021 n=63 Participants 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.	Sitagliptin n=40 Participants 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 n=61 Participants 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.
Change From Baseline to 6 Months in Fasting Plasma Glucose	-20.5 milligram per decililiter (mg/dL) Interval -34.3 to -6.6	-9.4 milligram per decililiter (mg/dL) Interval -26.3 to 7.4	6.6 milligram per decililiter (mg/dL) Interval -7.0 to 20.2

SECONDARY outcome

Timeframe: Baseline, 6 months

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

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.

Outcome measures

Outcome measures
Measure	LY2409021 n=63 Participants 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.	Sitagliptin n=40 Participants 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 n=68 Participants 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.
Change From Baseline to 6 Months in Blood Pressure Systolic Blood Pressure	6.1 millimeters of mercury (mm/Hg) Interval 2.7 to 9.5	1.1 millimeters of mercury (mm/Hg) Interval -2.9 to 5.2	1.8 millimeters of mercury (mm/Hg) Interval -1.5 to 5.1
Change From Baseline to 6 Months in Blood Pressure Diastolic Blood Pressure	2.9 millimeters of mercury (mm/Hg) Interval 0.7 to 5.0	0.3 millimeters of mercury (mm/Hg) Interval -2.3 to 2.9	1.5 millimeters of mercury (mm/Hg) Interval -0.6 to 3.6

SECONDARY outcome

Timeframe: Baseline, 6 months

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

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.

Outcome measures

Outcome measures
Measure	LY2409021 n=63 Participants 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.	Sitagliptin n=40 Participants 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 n=68 Participants 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.
Change From Baseline to 6 Months in Pulse Rate	1.5 beats per minutes (bpm) Interval -0.6 to 3.7	3.5 beats per minutes (bpm) Interval 0.9 to 6.0	1.2 beats per minutes (bpm) Interval -0.9 to 3.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	LY2409021 n=65 Participants 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.	Sitagliptin n=41 Participants 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 n=68 Participants 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.
Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG) Morning Pre-Meal	-29.4 mg/dL Standard Deviation 40.36	-8.13 mg/dL Standard Deviation 31.25	-4.31 mg/dL Standard Deviation 26.69
Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG) Mid-day Pre Meal	-28.43 mg/dL Standard Deviation 41.13	-30.58 mg/dL Standard Deviation 48.98	-9.30 mg/dL Standard Deviation 51.08
Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG) Morning 2 Hour (Hr) Post Meal	-38.8 mg/dL Standard Deviation 47.71	-30.76 mg/dL Standard Deviation 44.35	-18.28 mg/dL Standard Deviation 46.20
Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG) Midday 2 hr Post Meal	-24.22 mg/dL Standard Deviation 52.64	-25.20 mg/dL Standard Deviation 61.57	-10.49 mg/dL Standard Deviation 54.17
Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG) Evening Pre Meal	-24.58 mg/dL Standard Deviation 50.78	-16.78 mg/dL Standard Deviation 51.09	-14.13 mg/dL Standard Deviation 50.01
Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG) Evening 2 hr Post Meal	-28.36 mg/dL Standard Deviation 58.92	-21.12 mg/dL Standard Deviation 48.19	-9.50 mg/dL Standard Deviation 48.62
Change From Baseline to 6 Months in 7-Point Self-Monitoring of Blood Glucose (SMBG) Three AM	-22.78 mg/dL Standard Deviation 42.49	-20.12 mg/dL Standard Deviation 57.39	0.88 mg/dL Standard Deviation 41.94

SECONDARY outcome

Timeframe: Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,

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

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

Outcome measures

Outcome measures
Measure	LY2409021 n=65 Participants 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.	Sitagliptin 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 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.
Population Pharmacokinetics: Apparent Clearance of LY2409021	0.526 Liters per hour (L/h) Interval 0.454 to 0.598	—	—

SECONDARY outcome

Timeframe: Day 1 Month 1, 3, 6, 9, predose, 1 hour postdose,

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

Outcome measures

Outcome measures
Measure	LY2409021 n=65 Participants 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.	Sitagliptin 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 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.
Population Pharmacokinetics: Apparent Volume of Distribution of LY2409021	31.9 Liters (L) Interval 24.5 to 39.3	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	LY2409021 n=64 Participants 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.	Sitagliptin n=40 Participants 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 n=68 Participants 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.
Rate of Hypoglycemic Events Adjusted Per 30 Days	0.27 number of episodes per day	0.19 number of episodes per day	0.12 number of episodes per day

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	LY2409021 n=64 Participants 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.	Sitagliptin n=40 Participants 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 n=68 Participants 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.
Number of Participants With Hypoglycemic Events	20 Participants	40 Participants	68 Participants

Adverse Events

LY2409021

Serious events: 5 serious events

Other events: 26 other events

Deaths: 0 deaths

Sitagliptin

Serious events: 5 serious events

Other events: 22 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	LY2409021 n=65 participants at risk 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.	Sitagliptin n=41 participants at risk 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 n=68 participants at risk 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.
Cardiac disorders Acute coronary syndrome	0.00% 0/65 All randomized participants who received at least 1 dose of study drug.	2.4% 1/41 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Cardiac disorders Atrial fibrillation	0.00% 0/65 All randomized participants who received at least 1 dose of study drug.	2.4% 1/41 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Cardiac disorders Cardiac failure congestive	0.00% 0/65 All randomized participants who received at least 1 dose of study drug.	2.4% 1/41 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Cardiac disorders Ventricular extrasystoles	0.00% 0/65 All randomized participants who received at least 1 dose of study drug.	2.4% 1/41 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/65 All randomized participants who received at least 1 dose of study drug.	0.00% 0/41 All randomized participants who received at least 1 dose of study drug.	1.5% 1/68 • Number of events 1 All randomized participants who received at least 1 dose of study drug.
Infections and infestations Abscess limb	0.00% 0/65 All randomized participants who received at least 1 dose of study drug.	2.4% 1/41 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Infections and infestations Device related infection	1.5% 1/65 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/41 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	1.5% 1/65 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/41 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Infections and infestations Infectious colitis	1.5% 1/65 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/41 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Infections and infestations Pneumonia	1.5% 1/65 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/41 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/65 All randomized participants who received at least 1 dose of study drug.	2.4% 1/41 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/65 All randomized participants who received at least 1 dose of study drug.	2.4% 1/41 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	1.5% 1/65 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/41 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	1.5% 1/65 • Number of events 2 All randomized participants who received at least 1 dose of study drug.	0.00% 0/41 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Vascular disorders Hypertensive crisis	1.5% 1/65 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/41 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.
Vascular disorders Malignant hypertension	0.00% 0/65 All randomized participants who received at least 1 dose of study drug.	2.4% 1/41 • Number of events 1 All randomized participants who received at least 1 dose of study drug.	0.00% 0/68 All randomized participants who received at least 1 dose of study drug.