An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

AUC0-∞ is a measure of the mean concentration levels of drug in the plasma after the dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 \[100-300μg\]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.

Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 \[100-300μg\]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.

Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 \[100-300μg\]) is presented. No pharmacokinetic analysis was performed on participants receiving Placebo.

Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. A summary of pharmacokinetic parameters following administration of single SC (subcutaneous) injection of MK-8521 in healthy non-obese male participants (Part I, Panels A-B, Period 1-3 \[100-300μg\]) is presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part II, Panel C, D, and E) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, E and F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C-E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

AUC0-24hr is a measure of the mean concentration levels of drug in the plasma 0 to 24 hrs. after the dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

Trough plasma concentration (measured concentration at the end of a dosing interval at steady state \[taken directly before next administration\]). Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

Trough plasma concentration (measured concentration at the end of a dosing interval at steady state \[taken directly before next administration\]). Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections for the determination of plasma MK-8521 concentrations were collected at the following time points for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections occurred at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 10 Days (with dose escalation on Day 5) to healthy non-obese male participants (Part 2, Panel C, D, and E) are presented. Method of dispersion is coefficient of variation (%CV). Apparent terminal t1/2 was not reported for certain days since the terminal phase was not adequately captured with sampling up to 24hr post dose. No pharmacokinetic analysis was performed on participants receiving Placebo. Blood was collected for Part 2, Panel C, D, and E: Days 1, 4, 5, 9, 10 pre-dose; Days 1, 5, 10: 2, 4, 8, 10, 12, 16, 24 hrs. post dose; Day 10: 72, 96, 120 hrs. post-dose.

Apparent Terminal Half-life (t1/2) is the time required for a given drug concentration in the plasma to decrease by 50%. Mean pharmacokinetic parameter values for MK-8521 following administration of multiple subcutaneous once daily doses for 14 Days (with dose escalation on Day 7) to obese male participants (Part 2, Panel F) are presented. Method of dispersion is coefficient of variation (%CV). Apparent terminal t1/2 was not reported for certain days since the terminal phase was not adequately captured with sampling up to 24hr post dose. No pharmacokinetic analysis was performed on participants receiving Placebo. Blood collections occurred at the following time points for Part 2, Panel F: Days 1, 3, 4, 5, 7, 9, 11, 13, 14 pre-dose; Days 1, 7, 14: 0.5, 1, 2, 4, 8, 10, 12, 14, 16, 24 hrs. post-dose; Day 14: 72, 96, 120 hrs. post-dose.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Pancreatic beta cell sensitivity to ambient glucose concentration after a single dose of MK-8521 125μg/35μg or placebo at Tmax was quantified as the slope of insulin secretion rate relative to glucose concentration (ISR/G) during GGI (160 minutes duration) and assessed against MK-8521 average plasma concentration (Cave) during the GGI to preliminarily characterize the PK/ pharmacodynamic (PD) relationship. Study drug was administered on Day -1. Plasma concentrations of MK-8521 were determined at -10 min pre-GGI and 40, 80, 120 \& 160 min and blood concentrations of glucose, insulin \& C-peptide were determined at -10, -5 (pre-GGI), 20, 40, 60, 80, 100, 120, 140 \& 160 minutes after start of GGI on Day 1 of each period. ISR calculated by deconvolution of C-peptide concentrations using a two-compartmental model was regressed on glucose concentration via simple linear regression; beta cell glucose sensitivity was defined as slope from the regression line.