Single Ascending Dose Study of MK-1092 in Healthy Participants and in Participants With Type 1 and Type 2 Diabetes Mellitus (MK-1092-001)

There will be 4 parts in this study. In Part 1, healthy adult participants will be randomized
to receive blinded MK-1092 subcutaneously (SC) or glargine SC, as a single dose under the
euglycemic clamp. Once a safe and tolerated dose that achieves GIRmax is identified in Part
1, Part 2 will start. In Part 2, 4 different healthy adult participants will be enrolled in a
single panel and receive open-label MK-1092 SC as a single dose under the euglycemic clamp
and also receive an intravenous infusion of Humalog®. In Part 3, adult participants with T1DM
will be randomized to receive blinded MK-1092 SC or glargine SC, as a single dose under the
euglycemic clamp. Part 4 includes a 3-period design that will explore up to 3 single
subcutaneous doses of MK-1092 or glargine in participants with Type 2 diabetes mellitus.

Subject Inclusion Criteria

All participants

- Be a healthy male, or healthy female participant (excluding diabetes mellitus in Part
3 participants) of non-child bearing potential. A female non-child bearing potential
is one who is postmenopausal without menses for at least 1 year or whose status is
post hysterectomy, bilateral oophorectomy, or tubal ligation.

- Be judged to be in good health based on medical history, physical exam, vital sign
measurements, ECG and laboratory safety tests

- Have adequate venous access to support execution of trial procedures

For Parts 1 and 2 (Healthy adult participants)

- Healthy male and female participants between the ages of 18 and 50 years (inclusive)

- Have a Body Mass Index (BMI) ≥ 18.5 kg/m^2 and ≤ 28.0 kg/m^2 at screening

- Have fasting blood glucose values at screening must be < 100 mg/dL

- Be a nonsmoker and/or has not used nicotine or nicotine-containing products (e.g.,
nicotine patch) for at least approximately 3 months.

For Part 3 (Adult participants with T1DM):

- Be male, or female of non-childbearing potential between 18 to 60 years of age

- Have a diagnosis of T1DM as defined by standard diagnostic criteria for ≥ 12 months at
time of the pretrial (screening) visit

- Have a BMI ≥ 18.5 kg/m^2 and ≤ 32.0 kg/m^2 at screening.

- Be on stable doses of basal insulin over the 2-week period prior to screening and over
the 2 weeks prior to dosing

- Have a total daily insulin requirement (basal plus prandial) of ≤ 1.2 units/kg at
Screening

- Have a hemoglobin A1C (HbA1c) ≤ 10% at the screening visit.

- Be a non-smoker or smoker who uses no more than 5 cigarettes or equivalent (e.g.,
e-cigarettes) per day over the prior 3-month period also may be enrolled (at the
discretion of the investigator).

- Have a serum C-peptide concentration ≤ 0.7 ng/mL with a concurrent plasma glucose >90
mg/dL at screening or anytime within 24 weeks prior to screening.

For Part 4 (Adult participants with T2DM):

- Diagnosis of T2DM as defined by standard diagnostic criteria for >=12 months at time
of pretrial screening.

- Have a BMI >=18.5 kg/m2 and <=35.0 kg/m^2 at screening. BMI = mass (kg)/height (m)^2.

- Have a hemoglobin A1C (HbA1c) >=6.5% and <=10.0%.

- T2DM participants are not required to have been on insulin. If using insulin as
background therapy, subjects should have a total daily insulin requirement of <=1.2
units/kg, and have been on stable doses of basal insulin over the 2-week period prior
to screening and over the 2 weeks prior to dosing.

- Be a nonsmoker or smoker who uses no greater than 5 cigarettes or equivalent (e.g.,
e-cigarettes) daily over the prior 3-month period.

Subject Exclusion Criteria

All participants

- Is mentally or legally incapacitated

- Has a history of clinically significant endocrine (excluding diabetes mellitus in Part
3 participants), gastrointestinal, cardiovascular, hematological, hepatic,
immunological, renal, respiratory, genitourinary or major neurological (including
stroke and chronic seizures) abnormalities or diseases.

- Has a systolic blood pressure (SBP) ≥ 140 mm Hg and/or a diastolic blood pressure
(DBP) ≥ 90 mm Hg at screening.

- Is positive for hepatitis B surface antigen, hepatitis C antibodies or human
immunodeficiency virus (HIV) at screening.

- Has a history of cancer (malignancy) Exceptions: (1) Participants with adequately
treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix may
participate in the trial; (2) Participants with other malignancies which have been
successfully treated ≥10 years prior to the pretrial (screening) visit

- Has a history of significant multiple and/or severe allergies (e.g. food, drug, latex
allergy), or has had an anaphylactic reaction or significant intolerability (i.e.
systemic allergic reaction) to prescription or non-prescription drugs or food.

- Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4
weeks prior to the pretrial (screening) visit.

- Has participated in another investigational trial within 4 weeks.

- Has been randomized to, and received MK-5160 in prior clinical studies.

- Has a QTcF interval > 450 msec, has a history of risk factors for Torsades de Pointes
(e.g., heart failure/cardiomyopathy or family history of Long QT Syndrome).

- Has uncorrected hypokalemia

- Has uncorrected hypomagnesemia

- Is taking concomitant medications that prolong the QT/QTc interval.

- Is unable to refrain from or anticipates the use of any medication, including
prescription and non-prescription drugs or herbal remedies beginning approximately 2
weeks prior to administration of the initial dose of trial drug, throughout the trial,
until the posttrial visit.

- Has had a vaccination within 12 weeks of the pretrial visit.

- Consumes greater than 3 glasses of alcoholic beverages per day.

- Consumes excessive amounts, defined as greater than 6 servings caffeinated beverages
per day.

- Is currently a regular or recreational user of cannabis, any illicit drugs or has a
history of drug (including alcohol) abuse within approximately 6 months

- Has used systemic (intravenous, oral, inhaled) glucocorticoids within 3 months of
screening or is anticipated to require treatment with systemic glucocorticoids during
study participation.

For Part 1 and Part 2 (Healthy Adult Participants)

- Has an estimated creatinine clearance of < 90 mL/min based on Cockcroft-Gault equation

For Part 3 (Adult participants with T1DM):

- Has a history of diabetic ketoacidosis in the last 6 months prior to screening.

- Has an estimated creatinine clearance of < 60 mL/min based on the Cockcroft-Gault
equation at screening

- Has the diagnosis of hypoglycemia unawareness, or has had one or more severe
hypoglycemic episodes associated with hypoglycemic seizures, comas or unconsciousness
within 6 months prior to dosing.

- Has other major medical problems requiring medication (i.e., history of MI,
hypercholesterolemia).

- Has a known history of celiac disease or significant food allergy, at the discretion
of the investigator and Sponsor.

- Has a history of hypersensitivity to pharmacologic insulins or to any of the inactive
ingredients in recombinant human insulin, or to any E.coli-derived drug product.

For Part 4 (Adult participants with T2DM):

- Participant has an estimated creatinine clearance of < 60 mL/min based on the
Cockcroft-Gault equation.

- Has a history of diabetic ketoacidosis in the last 6 months prior to screening.

- Has the diagnosis of hypoglycemia unawareness, or has had one or more severe
hypoglycemic episodes associated with hypoglycemic seizures, comas or unconsciousness
within 6 months prior to dosing.

- Has a known history of celiac disease or significant food allergy, at the discretion
of the Investigator and Sponsor.

- Has been treated with a thiazolidinedione or injectable non-insulin anti-diabetic
therapy within the past three months prior to dosing.

- Has a history of hypersensitivity to pharmacologic insulins or to any of the inactive
ingredients in regular human insulin, or to any E.coli-derived drug product.