GLP-1 Peptide Atlas, by Delfa

← Trials/Trial dossier/NCT01982630

CompletedPhase 1Results posted

Study of the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Participants With Type 2 Diabetes Mellitus (MK-8521-003)

A Phase Ib, Multicenter, Placebo and Active- Comparator-Controlled, Randomized, Double-Blind, Clinical Trial to Evaluate the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Subjects With Type 2 Diabetes Mellitus

Lead sponsor

Merck Sharp & Dohme LLC

Asset

Liraglutide

Subcutaneous · GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

actual

Study population

Obesity / overweight, Type 2 diabetes

Key I/E criteria

•BMI 27-40•HbA1c 2-3%

Primary endpoints

•Treatment-emergent AEs (any)•Discontinuation due to AE•Heart rate, change

Identifiers

Registered as

NCT IDNCT01982630

Org study ID8521-003

Timeline

Milestones

Study start2013-11-07actual

Study first posted2013-11-13estimated

Primary completion2014-10-03actual

Study completion2014-10-03actual

Last update posted2022-03-08actual

Results first posted2022-03-08actual

Assets

Investigational agents

Liraglutide

Study populations

Who this study enrolls

Obesity / overweightType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

Maximum age65 Years

SexAll

Healthy volunteersAccepted

Inclusion criteria

•Male, or female of non-childbearing potential with Type 2 diabetes mellitus (Parts 1 and 2) or non-diabetic (Part 2)

•Body mass index (BMI) between: ≥27 and ≤40 kg/m^2

•A1C (average blood sugar for the past 2 to 3 months) value ≥7.0 and ≤11.0 % (Part 1) or ≥ 6.5 and ≤11.0 % (Part 2) at the time of screening (T2DM participants)

•A1C value <5.7 at the time of screening (non-diabetic subjects in Part 2 only)

•On a stable dose of metformin (≥1000 mg total daily dose) for at least 12 weeks at the time of screening (T2DM participants)

Exclusion criteria

•Mentally or legally incapacitated

•History of clinically significant psychiatric disorder of the last 5 years. Participants with situational depression may be enrolled in the trial at the discretion of the Investigator

•History of Type 1 diabetes mellitus or a history of ketoacidosis

•History of clinically significant gastrointestinal, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases

•History of cardiovascular disease or cardiac conduction disorder

•History of cancer (malignancy). Exceptions may include adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated ≥10 years prior to the pre-screening visit

•History of proliferative diabetic retinopathy or maculopathy

•Clinically significant diabetic autonomic neuropathy

•QTc interval ≥470 msec (for males) or ≥480 msec (for females)

•Clinical significant electrocardiogram (ECG) abnormality

•Positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)

•On a weight loss program and is not weight-stable (weight stable is defined history of <5% change in body weight in the last 3 months

•On a weight loss medication or has undergone bariatric surgery

•Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit

•Participated in another investigational trial within 4 weeks prior to the pretrial (screening) visit

•History of acute or chronic pancreatitis of any etiology

•Mean value for triplicate semi-recumbent systolic blood pressure >160 mm Hg and/or diastolic blood pressure >90 mm Hg (after at least a 10-minute seated rest) and blood pressure is considered unlikely to be below these limits by Day-1 (Randomization) with initiation or adjustment of antihypertensive medication

•Event of severe hypoglycemia with seizure or loss of consciousness in the past 12 months

•Treated with anti-hyperglycemic agents other than metformin within the last 12 weeks

•Previous exposure to any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g. Byetta™, Victoza™ or investigational agents)

Endpoints (102)

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

Safety / tolerability / PK

Cardiometabolic biomarkers

Glycemic / diabetes

24 endpoints

Secondary/registry result

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose on Days 1 (baseline) and 7

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), mg/dL	95% CI
Part 1: MK-8521 64/120 μg/Day	-23.57	—
Part 1: MK-8521 34/72 μg/Day	-39.00	—
Part 1: Liraglutide 0.6/1.2/1.8 mg/Day	-59.11	—
Part 1: Placebo for MK-8521	-11.13	—

Secondary/registry result

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose on Days 1 (baseline) and 14

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), mg/dL	95% CI
Part 1: MK-8521 64/120 μg/Day	-41.29	—
Part 1: MK-8521 34/72 μg/Day	-48.50	—
Part 1: Liraglutide 0.6/1.2/1.8 mg/Day	-59.25	—
Part 1: Placebo for MK-8521	-13.50	—

Secondary/registry result

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 7 dose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 1: MK-8521 64/120 μg/Day	-24.08	-45.46 – -2.71
Part 1: MK-8521 34/72 μg/Day	-27.54	-46.39 – -8.69
Part 1: Liraglutide 0.6/1.2/1.8 mg/Day	-53.64	-75.20 – -32.08
Part 1: Placebo for MK-8521	2.36	-16.20 – 20.92

Difference of Least Squares Means29.5690% CI4.34 – 54.77Linear Mixed Effects Model

Difference of Least Squares Means26.1090% CI2.02 – 50.19Linear Mixed Effects Model

Difference of Least Squares Means3.4590% CI-20.23 – 27.14Linear Mixed Effects Model

Difference of Least Squares Means-26.4590% CI-49.96 – -2.93Linear Mixed Effects Model

Difference of Least Squares Means-29.9090% CI-52.04 – -7.77Linear Mixed Effects Model

Difference of Least Squares Means-56.0090% CI-79.53 – -32.48Linear Mixed Effects Model

Secondary/registry result

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 1: MK-8521 64/120 μg/Day	-37.24	-58.61 – -15.86
Part 1: MK-8521 34/72 μg/Day	-45.63	-64.49 – -26.78
Part 1: Liraglutide 0.6/1.2/1.8 mg/Day	-52.20	-73.76 – -30.64
Part 1: Placebo for MK-8521	-2.00	-20.56 – 16.56

Difference of Least Squares Means14.9690% CI-10.25 – 40.18Linear Mixed Effects Model

Difference of Least Squares Means6.5790% CI-17.52 – 30.65Linear Mixed Effects Model

Difference of Least Squares Means8.4090% CI-15.29 – 32.08Linear Mixed Effects Model

Difference of Least Squares Means-35.2390% CI-58.75 – -11.72Linear Mixed Effects Model

Difference of Least Squares Means-43.6390% CI-65.77 – -21.50Linear Mixed Effects Model

Difference of Least Squares Means-50.2090% CI-73.72 – -26.68Linear Mixed Effects Model

Secondary/registry result

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose on Days 1 (baseline) and 14

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	-45.89	-56.44 – -35.33
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	-39.80	-48.27 – -31.33
Part 2: Placebo for MK-8521-T2DM	-14.69	-43.93 – 14.55

Difference of Least Squares Means-31.2090% CI-56.59 – -5.81Linear Mixed Effects Model

Difference of Least Squares Means-25.1290% CI-50.25 – 0.01Linear Mixed Effects Model

Difference of Least Squares Means-6.0890% CI-17.31 – 5.14Linear Mixed Effects Model

Secondary/registry result

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose on Days 1 (baseline) and 19

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	-44.22	-54.77 – -33.66
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	-47.33	-55.80 – -38.86
Part 2: Placebo for MK-8521-T2DM	-16.74	-45.98 – 12.51

Difference of Least Squares Means-27.4890% CI-52.87 – -2.09Linear Mixed Effects Model

Difference of Least Squares Means-30.5990% CI-55.72 – -5.46Linear Mixed Effects Model

Difference of Least Squares Means3.1190% CI-8.11 – 14.34Linear Mixed Effects Model

Secondary/registry result

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose on Days 1 (baseline) and 24

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	-40.14	-51.00 – -29.27
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	-50.14	-59.30 – -40.99
Part 2: Placebo for MK-8521-T2DM	-44.73	-73.97 – -15.49

Difference of Least Squares Means4.5990% CI-20.88 – 30.06Linear Mixed Effects Model

Difference of Least Squares Means-5.4290% CI-30.68 – 19.85Linear Mixed Effects Model

Difference of Least Squares Means10.0190% CI-1.77 – 21.78Linear Mixed Effects Model

Secondary/registry result

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose on Days 1 (baseline) and 29

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	-52.54	-63.74 – -41.33
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	-52.06	-61.21 – -42.91
Part 2: Placebo for MK-8521-T2DM	-37.55	-66.80 – -8.31

Difference of Least Squares Means-14.9890% CI-40.53 – 10.57Linear Mixed Effects Model

Difference of Least Squares Means-14.5090% CI-39.77 – 10.76Linear Mixed Effects Model

Difference of Least Squares Means-0.4890% CI-12.47 – 11.52Linear Mixed Effects Model

Secondary/registry result

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	-47.52	-56.82 – -38.22
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	-51.24	-58.02 – -44.45
Part 2: Placebo for MK-8521-T2DM	-3.84	-30.31 – 22.63

Difference of Least Squares Means-43.6890% CI-65.81 – -21.55Linear Mixed Effects Model

Difference of Least Squares Means-47.4090% CI-69.35 – -25.45Linear Mixed Effects Model

Difference of Least Squares Means3.7290% CI-5.76 – 13.19Linear Mixed Effects Model

Secondary/registry result

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 19 dose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	-52.23	-61.54 – -42.93
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	-57.43	-64.21 – -50.64
Part 2: Placebo for MK-8521-T2DM	-18.22	-44.69 – 8.25

Difference of Least Squares Means-34.0190% CI-56.14 – -11.88Linear Mixed Effects Model

Difference of Least Squares Means-39.2090% CI-61.15 – -17.26Linear Mixed Effects Model

Difference of Least Squares Means5.2090% CI-4.28 – 14.67Linear Mixed Effects Model

Secondary/registry result

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 24 dose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	-50.44	-59.89 – -40.99
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	-60.66	-67.60 – -53.72
Part 2: Placebo for MK-8521-T2DM	-26.71	-53.18 – -0.24

Difference of Least Squares Means-23.7390% CI-45.89 – -1.56Linear Mixed Effects Model

Difference of Least Squares Means-33.9590% CI-55.93 – -11.98Linear Mixed Effects Model

Difference of Least Squares Means10.2390% CI0.56 – 19.89Linear Mixed Effects Model

Secondary/registry result

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 29 dose

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	-53.44	-62.89 – -43.99
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	-59.72	-66.66 – -52.78
Part 2: Placebo for MK-8521-T2DM	-29.96	-56.43 – -3.49

Difference of Least Squares Means-23.4990% CI-45.65 – -1.32Linear Mixed Effects Model

Difference of Least Squares Means-29.7690% CI-51.74 – -7.79Linear Mixed Effects Model

Difference of Least Squares Means6.2790% CI-3.39 – 15.93Linear Mixed Effects Model

Secondary/protocol endpoint

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose on Days 1 (baseline) and 7

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose on Days 1 (baseline) and 14

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 7 dose

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose on Days 1 (baseline) and 14

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose on Days 1 (baseline) and 19

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose on Days 1 (baseline) and 24

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose on Days 1 (baseline) and 29

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 14 dose

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 19 dose

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 24 dose

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in 24-hour Weighted Mean Glucose (WMG) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose and before food on Day 1) and up to 24 hours post Day 29 dose

change from baseline, improvement

Cardiometabolic biomarkers

34 endpoints

Primary/registry result

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 1: MK-8521 64/120 μg/Day	7.19	3.48 – 10.89
Part 1: MK-8521 34/72 μg/Day	1.17	-2.21 – 4.55
Part 1: Liraglutide 0.6/1.2/1.8 mg/Day	7.42	3.74 – 11.09
Part 1: Placebo for MK-8521	5.69	2.39 – 8.99

Difference of Least Squares Means-0.2390% CI-4.59 – 4.13Linear Mixed Effects Model

Difference of Least Squares Means-6.2590% CI-10.48 – -2.01Linear Mixed Effects Model

Difference of Least Squares Means6.0290% CI1.81 – 10.22Linear Mixed Effects Model

Difference of Least Squares Means1.5090% CI-2.65 – 5.64Linear Mixed Effects Model

Difference of Least Squares Means-4.5290% CI-8.52 – -0.52Linear Mixed Effects Model

Difference of Least Squares Means1.7390% CI-2.38 – 5.83Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	1.99	0.10 – 3.88
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	4.10	1.87 – 6.34
Part 2: Placebo for MK-8521-T2DM	-0.54	-3.80 – 2.73

Difference of Least Squares Means-2.1190% CI-4.55 – 0.32Linear Mixed Effects Model

Difference of Least Squares Means2.5390% CI-0.61 – 5.66Linear Mixed Effects Model

Difference of Least Squares Means4.6490% CI1.35 – 7.93Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 1: MK-8521 64/120 μg/Day	9.67	5.97 – 13.37
Part 1: MK-8521 34/72 μg/Day	3.90	0.52 – 7.28
Part 1: Liraglutide 0.6/1.2/1.8 mg/Day	10.32	6.65 – 14.00
Part 1: Placebo for MK-8521	9.81	6.51 – 13.12

Difference of Least Squares Means-0.6590% CI-5.01 – 3.71Linear Mixed Effects Model

Difference of Least Squares Means-6.4290% CI-10.66 – -2.19Linear Mixed Effects Model

Difference of Least Squares Means5.7790% CI1.57 – 9.97Linear Mixed Effects Model

Difference of Least Squares Means-0.1590% CI-4.29 – 4.00Linear Mixed Effects Model

Difference of Least Squares Means-5.9190% CI-9.91 – -1.92Linear Mixed Effects Model

Difference of Least Squares Means0.5190% CI-3.60 – 4.62Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	5.05	2.79 – 7.30
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	5.93	3.27 – 8.60
Part 2: Placebo for MK-8521-T2DM	-0.20	-4.32 – 3.93

Difference of Least Squares Means-0.8990% CI-3.80 – 2.02Linear Mixed Effects Model

Difference of Least Squares Means5.2490% CI1.34 – 9.15Linear Mixed Effects Model

Difference of Least Squares Means6.1390% CI2.05 – 10.22Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 19 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 19 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	5.62	3.19 – 8.05
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	6.20	3.32 – 9.07
Part 2: Placebo for MK-8521-T2DM	-2.14	-6.66 – 2.37

Difference of Least Squares Means-0.5790% CI-3.71 – 2.57Linear Mixed Effects Model

Difference of Least Squares Means7.7790% CI3.50 – 12.03Linear Mixed Effects Model

Difference of Least Squares Means8.3490% CI3.89 – 12.79Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 24 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 24 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	7.30	4.43 – 10.17
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	5.95	2.50 – 9.41
Part 2: Placebo for MK-8521-T2DM	-0.99	-6.28 – 4.29

Difference of Least Squares Means1.3590% CI-2.40 – 5.09Linear Mixed Effects Model

Difference of Least Squares Means8.2990% CI3.29 – 13.30Linear Mixed Effects Model

Difference of Least Squares Means6.9590% CI1.69 – 12.20Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 29 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 29 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	8.30	5.31 – 11.29
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	5.84	2.26 – 9.43
Part 2: Placebo for MK-8521-T2DM	-1.31	-6.81 – 4.19

Difference of Least Squares Means2.4690% CI-1.42 – 6.34Linear Mixed Effects Model

Difference of Least Squares Means9.6190% CI4.42 – 14.81Linear Mixed Effects Model

Difference of Least Squares Means7.1590% CI1.70 – 12.60Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Peak Heart Rate (PHR) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	7.94	5.76 – 10.13
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	11.91	9.30 – 14.53
Part 2: Placebo for MK-8521-T2DM	8.65	4.86 – 12.43

Difference of Least Squares Means-3.9790% CI-6.80 – -1.14Linear Mixed Effects Model

Difference of Least Squares Means-0.7090% CI-4.33 – 2.93Linear Mixed Effects Model

Difference of Least Squares Means3.2690% CI-0.54 – 7.06Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Peak Heart Rate (PHR) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	11.41	8.50 – 14.32
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	13.00	9.58 – 16.41
Part 2: Placebo for MK-8521-T2DM	8.90	3.87 – 13.93

Difference of Least Squares Means-1.5890% CI-5.31 – 2.15Linear Mixed Effects Model

Difference of Least Squares Means2.5290% CI-2.32 – 7.35Linear Mixed Effects Model

Difference of Least Squares Means4.1090% CI-0.96 – 9.16Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Peak Heart Rate (PHR) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 19 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	11.26	8.28 – 14.24
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	14.75	11.25 – 18.25
Part 2: Placebo for MK-8521-T2DM	7.30	2.00 – 12.61

Difference of Least Squares Means-3.4890% CI-7.31 – 0.34Linear Mixed Effects Model

Difference of Least Squares Means3.9690% CI-1.11 – 9.03Linear Mixed Effects Model

Difference of Least Squares Means7.4490% CI2.16 – 12.73Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Peak Heart Rate (PHR) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 24 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	14.09	10.60 – 17.57
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	14.06	9.85 – 18.27
Part 2: Placebo for MK-8521-T2DM	9.39	3.03 – 15.76

Difference of Least Squares Means0.0390% CI-4.51 – 4.57Linear Mixed Effects Model

Difference of Least Squares Means4.7090% CI-1.33 – 10.73Linear Mixed Effects Model

Difference of Least Squares Means4.6690% CI-1.67 – 11.00Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Peak Heart Rate (PHR) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 29 dose

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	16.01	12.88 – 19.13
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	12.66	8.91 – 16.41
Part 2: Placebo for MK-8521-T2DM	7.13	1.49 – 12.76

Difference of Least Squares Means3.3490% CI-0.70 – 7.39Linear Mixed Effects Model

Difference of Least Squares Means8.8890% CI3.53 – 14.23Linear Mixed Effects Model

Difference of Least Squares Means5.5490% CI-0.08 – 11.15Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 7 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 8 (24 hours after Day 7)

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	1.65	-1.00 – 4.29
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	5.20	2.07 – 8.33
Part 2: Placebo for MK-8521-T2DM	0.59	-3.99 – 5.18

Difference of Least Squares Means-3.5590% CI-6.98 – -0.12Linear Mixed Effects Model

Difference of Least Squares Means1.0590% CI-3.38 – 5.49Linear Mixed Effects Model

Difference of Least Squares Means4.6190% CI-0.02 – 9.23Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 14 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 15 (24 hours after Day 14)

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	4.22	1.58 – 6.87
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	5.38	2.25 – 8.51
Part 2: Placebo for MK-8521-T2DM	-4.42	-9.32 – 0.47

Difference of Least Squares Means-1.1690% CI-4.59 – 2.28Linear Mixed Effects Model

Difference of Least Squares Means8.6590% CI3.99 – 13.31Linear Mixed Effects Model

Difference of Least Squares Means9.8090% CI4.96 – 14.65Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 19 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 20 (24 hours after Day 19)

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	6.41	3.76 – 9.05
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	10.44	7.24 – 13.65
Part 2: Placebo for MK-8521-T2DM	-3.82	-8.72 – 1.07

Difference of Least Squares Means-4.0490% CI-7.52 – -0.56Linear Mixed Effects Model

Difference of Least Squares Means10.2390% CI5.57 – 14.89Linear Mixed Effects Model

Difference of Least Squares Means14.2790% CI9.38 – 19.15Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 24 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 25 (24 hours after Day 24)

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	7.51	4.77 – 10.25
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	9.63	6.35 – 12.91
Part 2: Placebo for MK-8521-T2DM	-5.82	-10.72 – -0.93

Difference of Least Squares Means-2.1290% CI-5.70 – 1.47Linear Mixed Effects Model

Difference of Least Squares Means13.3490% CI8.64 – 18.03Linear Mixed Effects Model

Difference of Least Squares Means15.4590% CI10.53 – 20.38Linear Mixed Effects Model

Primary/registry result

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 29 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 30 (24 hours after Day 29)

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Beats per minute	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	9.41	6.67 – 12.15
Part 2: Liraglutide 0.6/1.2/1.8 mg/Day-T2DM	7.30	4.01 – 10.58
Part 2: Placebo for MK-8521-T2DM	-1.02	-5.92 – 3.87

Difference of Least Squares Means2.1190% CI-1.47 – 5.70Linear Mixed Effects Model

Difference of Least Squares Means10.4390% CI5.73 – 15.13Linear Mixed Effects Model

Difference of Least Squares Means8.3290% CI3.40 – 13.24Linear Mixed Effects Model

Primary/protocol endpoint

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 7 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 14 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 19 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 19 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 24 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 24 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Time-weighted Average From 0 to 24 Hours (TWA0-24hr) of Heart Rate (HR) After 29 Days of Treatment in Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 29 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Peak Heart Rate (PHR) at Day 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 7 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Peak Heart Rate (PHR) at Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 14 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Peak Heart Rate (PHR) at Day 19 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 19 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Peak Heart Rate (PHR) at Day 24 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 24 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Peak Heart Rate (PHR) at Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and up to 24 hours post Day 29 dose

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 7 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 8 (24 hours after Day 7)

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 14 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 15 (24 hours after Day 14)

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 19 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 20 (24 hours after Day 19)

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 24 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 25 (24 hours after Day 24)

Heart rate, change

change from baseline, improvement

Primary/protocol endpoint

Change From Baseline in Resting Morning Heart Rate (RMHR) After the Day 29 Dose for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Baseline (predose Day 1) and Day 30 (24 hours after Day 29)

Heart rate, change

change from baseline, improvement

Safety / tolerability / PK

44 endpoints

Primary/registry result

Number of Participants Experiencing Adverse Events (AEs) in Part 1

Time frame:Up to approximately 42 days

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Part 1: MK-8521 64 μg/Day	5	—
Part 1: MK-8521 120 μg/Day	5	—
Part 1: MK-8521 34 μg/Day	1	—
Part 1: MK-8521 72 μg/Day	4	—
Part 1: Liraglutide 0.6 mg/Day	2	—
Part 1: Liraglutide 1.2 mg/Day	7	—
Part 1: Liraglutide 1.8 mg/Day	2	—
Part 1: Placebo for MK-8521	5	—

Primary/registry result

Number of Participants Experiencing Adverse Events (AEs) in Part 2

Time frame:Up to approximately 57 days

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Part 2: MK-8521 64 μg/Day	8	—
Part 2: MK-8521 120 μg/Day	14	—
Part 2: MK-8521 180 μg/Day	6	—
Part 2: MK-8521 240 μg/Day	13	—
Part 2: MK-8521 300 μg/Day	8	—
Part 2: Liraglutide 0.6 mg/Day	8	—
Part 2: Liraglutide 1.2 mg/Day	8	—
Part 2: Liraglutide 1.8 mg/Day	12	—
Part 2: Placebo for MK-8521-T2DM	3	—
Part 2: MK-8521 64 µg/Day-Non-Diabetic Overweight/Obese	2	—
Part 2: MK-8521 120 µg/Day-Non-Diabetic Overweight/Obese	4	—

Primary/registry result

Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 1

Time frame:Up to approximately 14 days

Discontinuation due to AE

event count, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Part 1: MK-8521 64 μg/Day	2	—
Part 1: MK-8521 120 μg/Day	0	—
Part 1: MK-8521 34 μg/Day	0	—
Part 1: MK-8521 72 μg/Day	0	—
Part 1: Liraglutide 0.6 mg/Day	1	—
Part 1: Liraglutide 1.2 mg/Day	0	—
Part 1: Liraglutide 1.8 mg/Day	0	—
Part 1: Placebo for MK-8521	0	—

Primary/registry result

Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 2

Time frame:Up to approximately 29 days

Discontinuation due to AE

event count, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Part 2: MK-8521 64 μg/Day	0	—
Part 2: MK-8521 120 μg/Day	0	—
Part 2: MK-8521 180 μg/Day	0	—
Part 2: MK-8521 240 μg/Day	1	—
Part 2: MK-8521 300 μg/Day	0	—
Part 2: Liraglutide 0.6 mg/Day	0	—
Part 2: Liraglutide 1.2 mg/Day	1	—
Part 2: Liraglutide 1.8 mg/Day	1	—
Part 2: Placebo for MK-8521-T2DM	1	—
Part 2: MK-8521 64 µg/Day-Non-Diabetic Overweight/Obese	0	—
Part 2: MK-8521 120 µg/Day-Non-Diabetic Overweight/Obese	0	—

Primary/registry result

Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1, 7, and 14

AUC₀–∞

concentration, descriptive

Posted result

Group	Value (geometric_mean), nM•hour	95% CI
Part 1: MK-8521 64/120 μg/DayDay 1	6.11	—
Day 7	14.4	—
Day 14	32.8	—
Part 1: MK-8521 34/72 μg/DayDay 1	2.25	—
Day 7	5.63	—
Day 14	12.6	—

Primary/registry result

Maximum Concentration (Cmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Cmax

concentration, descriptive

Posted result

Group	Value (geometric_mean), nM	95% CI
Part 1: MK-8521 64/120 μg/DayDay 1	0.350	—
Day 7	0.710	—
Part 1: MK-8521 34/72 μg/DayDay 1	0.128	—
Day 7	0.275	—

Primary/registry result

Maximum Concentration (Cmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

Cmax

concentration, descriptive

Posted result

Group	Value (geometric_mean), nM	95% CI
Part 1: MK-8521 64/120 μg/Day	1.70	—
Part 1: MK-8521 34/72 μg/Day	0.619	—

Primary/registry result

Trough Concentration (Ctrough) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose on Days 2, 7, and 14

Plasma concentration (steady state)

concentration, descriptive

Posted result

Group	Value (geometric_mean), nM	95% CI
Part 1: MK-8521 64/120 μg/DayDay 1	0.322	—
Day 7	0.442	—
Day 14	1.16	—
Part 1: MK-8521 34/72 μg/DayDay 1	0.119	—
Day 7	0.207	—
Day 14	0.506	—

Primary/registry result

Time to Maximum Concentration (Tmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Tmax

descriptive

Posted result

Group	Value (median), Hours	95% CI
Part 1: MK-8521 64/120 μg/DayDay 1	16	10 – 24
Day 7	7	6 – 10
Part 1: MK-8521 34/72 μg/DayDay 1	16	10 – 24
Day 7	6	1 – 10

Primary/registry result

Time to Maximum Concentration (Tmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

Tmax

concentration, descriptive

Posted result

Group	Value (median), Hours	95% CI
Part 1: MK-8521 64/120 μg/Day	8	1 – 8
Part 1: MK-8521 34/72 μg/Day	6	4 – 12

Primary/registry result

Apparent Terminal Half Life (t1/2) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Half-life

descriptive

Primary/registry result

Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

Half-life

descriptive

Posted result

Group	Value (geometric_mean), Hours	95% CI
Part 1: MK-8521 64/120 μg/Day	15.6	—
Part 1: MK-8521 34/72 μg/Day	17.2	—

Primary/registry result

Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

AUC₀–∞

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio	95% CI
Part 1: MK-8521 64/120 μg/Day	2.31	1.85 – 2.66
Part 1: MK-8521 34/72 μg/Day	2.50	1.80 – 3.73

Primary/registry result

Accumulation Ratio of the Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Cmax

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio	95% CI
Part 1: MK-8521 64/120 μg/Day	2.00	1.41 – 2.35
Part 1: MK-8521 34/72 μg/Day	2.14	1.61 – 2.83

Primary/registry result

Accumulation Ratio of the Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose on Days 2 and 7

Plasma concentration (steady state)

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio	95% CI
Part 1: MK-8521 64/120 μg/Day	1.37	0.39 – 2.13
Part 1: MK-8521 34/72 μg/Day	1.73	1.46 – 1.93

Primary/registry result

Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

Time frame:Predose and 1, 2, 6, 10, 16, and 24 hours postdose on Days 1, 7, and 14

AUC₀–∞

concentration, descriptive

Posted result

Group	Value (geometric_mean), nM•hour	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DMDay 1	6.46	—
Day 7	15.1	—
Day 14	30.0	—
Part 2: MK-8521 64/120 µg/Day-Non-Diabetic Overweight/ObeseDay 1	7.68	—
Day 7	15.0	—
Day 14	34.4	—

Primary/registry result

Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

Time frame:Predose and 1, 2, 6, 10, 16, and 24 hours post-dose on Days 1 and 7

AUC₀–∞

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio	95% CI
Part 2: MK-8521 64/120/180/240/300 µg/Day-T2DM	2.33	—
Part 2: MK-8521 64/120 µg/Day-Non-Diabetic Overweight/Obese	1.95	—

Primary/protocol endpoint

Number of Participants Experiencing Adverse Events (AEs) in Part 1

Time frame:Up to approximately 42 days

Treatment-emergent AEs (any)

event count, event

Primary/protocol endpoint

Number of Participants Experiencing Adverse Events (AEs) in Part 2

Time frame:Up to approximately 57 days

Treatment-emergent AEs (any)

event count, event

Primary/protocol endpoint

Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 1

Time frame:Up to approximately 14 days

Discontinuation due to AE

event count, event

Primary/protocol endpoint

Number of Participants Discontinuing Study Drug Due to Adverse Events (AEs) in Part 2

Time frame:Up to approximately 29 days

Discontinuation due to AE

event count, event

Primary/protocol endpoint

Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1, 7, and 14

AUC₀–∞

concentration, descriptive

Primary/protocol endpoint

Maximum Concentration (Cmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Cmax

concentration, descriptive

Primary/protocol endpoint

Maximum Concentration (Cmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

Cmax

concentration, descriptive

Primary/protocol endpoint

Trough Concentration (Ctrough) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose on Days 2, 7, and 14

Plasma concentration (steady state)

concentration, descriptive

Primary/protocol endpoint

Time to Maximum Concentration (Tmax) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Tmax

concentration, descriptive

Primary/protocol endpoint

Time to Maximum Concentration (Tmax) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

Tmax

descriptive

Primary/protocol endpoint

Apparent Terminal Half Life (t1/2) of MK-8521 on Days 1 and 7 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Half-life

descriptive

Primary/protocol endpoint

Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, 24, 72, 96, and 120 hours post-dose on Day 14

Half-life

descriptive

Primary/protocol endpoint

Accumulation Ratio of the Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

AUC₀–∞

ratio, descriptive

Primary/protocol endpoint

Accumulation Ratio of the Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose and 1, 2, 4, 6, 8, 10, 12, 16, and 24 hours post-dose on Days 1 and 7

Cmax

ratio, descriptive

Primary/protocol endpoint

Accumulation Ratio of the Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 1

Time frame:Predose on Days 2 and 7

Plasma concentration (steady state)

ratio, descriptive

Primary/protocol endpoint/low confidence

Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24hr) of MK-8521 on Days 1, 7, and 14 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

Time frame:Predose and 1, 2, 6, 10, 16, and 24 hours postdose on Days 1, 7, and 14

concentration, descriptive

Primary/protocol endpoint

Time frame:Predose and 1, 2, 6, 10, 16, and 24 hours post-dose on Days 1 and 7

AUC₀–∞

ratio, descriptive

Secondary/registry result

Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

Time frame:Predose and 1, 2, 6, 10, 16, 24 hours post dose on Days 1, 7, 14, 19, 24 (T2DM) and Days 1 and 7 (Non-Diabetic Overweight/Obese); predose and 1, 2, 6, 10, 16, 24, 72, 96. and 120 hours post dose on Day 14 (Non-Diabetic Overweight/Obese) and Day 29 (T2DM).

Cmax

concentration, descriptive

Posted result

Group	Value (geometric_mean), nM	95% CI
Part 2: MK-8521 64/120/180/240/300 μg/Day-T2DMDay 1	0.35	—
Day 7	0.719	—
Day 14	1.43	—
Day 19	2.27	—
Day 24	2.85	—
Day 29	3.14	—
Part 2: MK-8521 64/120 μg/Day-Non-Diabetic Overweight/ObeseDay 1	0.411	—
Day 7	0.742	—
Day 14	1.72	—

Secondary/registry result

Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

Time frame:Predose on Days 2 (sampled 24 hours after Day 1 dose) and 7, 14, 19, 24, and 29

Plasma concentration (steady state)

concentration, descriptive

Posted result

Group	Value (geometric_mean), nM	95% CI
Part 2: MK-8521 64/120/180/240/300 μg/Day-T2DMDay 1	0.331	—
Day 7	0.533	—
Day 14	1.07	—
Day 19	1.61	—
Day 24	2.02	—
Day 29	2.47	—
Part 2: MK-8521 64/120 μg/Day-Non-Diabetic Overweight/ObeseDay 1	0.388	—
Day 7	0.492	—
Day 14	1.12	—

Secondary/registry result

Time to Maximum Concentration (Tmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

Tmax

descriptive

Posted result

Group	Value (median), Hours	95% CI
Part 2: MK-8521 64/120/180/240/300 μg/Day-T2DMDay 1	16	10 – 24
Day 7	10	1 – 16
Day 14	6	1 – 10
Day 19	6	6 – 10
Day 24	6	6 – 16
Day 29	10	1 – 24
Part 2: MK-8521 64/120 μg/Day-Non-Diabetic Overweight/ObeseDay 1	16	10 – 24
Day 7	10	10 – 10
Day 14	6	6 – 10

Secondary/registry result

Apparent Terminal Half Life (t1/2) of MK-8521 on Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose and 1, 2, 6, 10, 16, 24, 72, 96 and 120 hours post dose on Day 29

Half-life

descriptive

Posted result

Group	Value (geometric_mean), Hours	95% CI
Part 2: MK-8521 64/120/180/240/300 μg/Day-T2DM	15.4	—

Secondary/registry result

Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Non-Diabetic Overweight/Obese Participants in Part 2

Time frame:Predose and 1, 2, 6, 10, 16, and 24 hours post dose on Day 14

Half-life

descriptive

Posted result

Group	Value (geometric_mean), Hours	95% CI
Part 2: MK-8521 64/120 μg/Day-Non-Diabetic Overweight/Obese	14.4	—

Secondary/protocol endpoint

Maximum Concentration (Cmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

Cmax

concentration, descriptive

Secondary/protocol endpoint

Trough Concentration (Ctrough) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

Time frame:Predose on Days 2 (sampled 24 hours after Day 1 dose) and 7, 14, 19, 24, and 29

Plasma concentration (steady state)

concentration, descriptive

Secondary/protocol endpoint

Time to Maximum Concentration (Tmax) of MK-8521 for Type 2 Diabetes Mellitus (T2DM) and Non-Diabetic Overweight/Obese Participants in Part 2

Tmax

descriptive

Secondary/protocol endpoint

Apparent Terminal Half Life (t1/2) of MK-8521 on Day 29 for Type 2 Diabetes Mellitus (T2DM) Participants in Part 2

Time frame:Predose and 1, 2, 6, 10, 16, 24, 72, 96 and 120 hours post dose on Day 29

Half-life

descriptive

Secondary/protocol endpoint

Apparent Terminal Half Life (t1/2) of MK-8521 on Day 14 for Non-Diabetic Overweight/Obese Participants in Part 2

Time frame:Predose and 1, 2, 6, 10, 16, and 24 hours post dose on Day 14

Half-life

descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

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