Trial to Learn About the Study Medicine (PF-07081532) and Rybelsus in People With Type 2 Diabetes and Separately PF-07081532 in People With Obesity

A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED, DOSE RANGING, DOSE FINDING, PARALLEL GROUP STUDY TO ASSESS EFFICACY AND SAFETY OF PF-07081532, AND OPEN LABEL ORAL SEMAGLUTIDE, IN ADULTS WITH TYPE 2 DIABETES MELLITUS (T2DM) INADEQUATELY CONTROLLED ON METFORMIN, AND SEPARATELY PF-07081532 COMPARED TO MATCHING PLACEBO IN ADULTS WITH OBESITY BUT WITHOUT T2DM

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05579977

Enrollment

902

Registered

2022-10-14

Start date

2022-10-27

Completion date

2023-09-22

Last updated

2024-08-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Obesity

Keywords

Diabetes Mellitus, Obesity

Brief summary

The purpose of this study is to find out if PF-07081532 (the active study drug), is safe and helps treat people with obesity without diabetes to lose weight, and people with diabetes to keep their blood sugar in good control. Individuals diagnosed with diabetes that are on metformin or individuals with obesity without diabetes will be included in the study. Those participating in the diabetes part of the study, will receive either active study drug, placebo, or an approved treatment called Rybelsus. Those in the obesity part of the study, will receive either active study drug or placebo. The study will last for about 36 weeks except for the first 25% of the participants that enter in which case the study will last for approximately 48 weeks. during this time there will be visits every 4 weeks with phone calls in between.

Interventions

DRUGPF-07081532

Oral glucagon-like peptide-1 receptor agonist

OTHERPlacebo

No drug

DRUGRybelsus

Oral Semaglutide

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

T2DM * T2DM inadequately controlled with metformin * BMI ≥23.0 kg/m2 (≥20.0 kg/m2 in Japan) * HbA1C of 7% to 10% (53-86 mmol/mol) * FPG ≤270 mg/dL (15 mmol/L) Obesity * BMI ≥30.0 kg/m2 * HbA1C ≤6.4% (47 mmol/mol) * FPG ≤126 mg/dL (7 mmol/L)

Exclusion criteria

* Any of the following: Active/current, symptomatic gallbladder disease; History of pancreatitis in the prior 2-months;History of Type 1 Diabetes Mellitus, or secondary forms of diabetes; Any condition affecting drug absorption; Medical history of active liver disease (other than non-alcoholic hepatic steatosis) * Use of pharmacological agents with approved indication for weight loss * T2DM:Use of any agent (other than metformin)for the explicit purpose of glycemic control;History of diabetic ketoacidosis;Proliferative retinopathy or maculopathy requiring acute treatment; * Obesity: Previous or planned weight reduction surgery; Major depressive disorder or other severe psychiatric disorders; Any lifetime history of a suicide attempt; PHQ-9 score ≥15; Response of yes to Question 4 or 5, or on any suicidal behavioral question on the C-SSRS * Clinically significant cardiovascular conditions * Uncontrolled blood pressure * Personal or within first-degree relative family history of MTC or MEN2 * Other medical or psychiatric condition that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study * Any of the following central lab results: Fasting C-peptide \<0.8 ng/mL; ALT or AST ≥2.5x ULN; Direct bilirubin \>ULN or T Bili \>1.5x ULN except when participants have a history of Gilbert syndrome ; TSH \>1.5x ULN or \<LLN; Serum calcitonin \>ULN; Serum amylase or serum lipase \>ULN; eGFR \<45 ml/min/1.73 ; Active Hepatitis B, or Hepatitis C; A positive urine drug test for illicit drugs

Design outcomes

Primary

Measure	Time frame	Description
Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)	Baseline (result closest prior to dosing on Day 1), Week 32	—
Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 32: Cohort 2 (Obesity)	Baseline (result closest prior to dosing on Day 1), week 32	Body weight was measured using a calibrated weighing scale.

Secondary

Measure	Time frame	Description
Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 32: Cohort 2 (Obesity)	Baseline (result closest prior to dosing on Day 1), Week 32	HOMA-S was calculated as (22.5/\[FPI\] \* FPG) \*100 and measured in terms of percentage sensitivity.
Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Up to week 28	Glucose values were monitored using glucometer. Hypoglycemia =plasma/blood glucose value of \<70 mg/dL (3.9 millimoles per liter \[mmol/L\]). Severe HAE: Participant was unable to treat him/herself due to neurological impairment (not age) and required assistance of another person, at least one neurological symptom of memory loss, confusion, uncontrolled behavior etc. Either documented blood glucose\<=54 mg/dL (2.7 mmol/L). Documented symptomatic: An event during which symptoms of HAE were accompanied with plasma/blood glucose \<70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Probable symptomatic HAE: An event during which symptoms of an HAE were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose concentration \<70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Asymptomatic: An event not accompanied by typical symptoms of an HAE, but a plasma/blood glucose value of \<70 mg/dL was reported.
Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Up to week 28	Glucose values were monitored using glucometer. Hypoglycemia =plasma/blood glucose value of \<70 mg/dL (3.9 mmol/L). Severe HAE: Participant was unable to treat him/herself due to neurological impairment (not age) and required assistance of another person, at least one neurological symptom of memory loss, confusion, uncontrolled behavior etc. Either documented blood glucose\<=54 mg/dL (2.7 mmol/L). Documented symptomatic: An event during which symptoms of HAE were accompanied with plasma/blood glucose \<70 mg/dL u and prompt resolution with food intake, SC glucagon, or IV glucose. Probable symptomatic HAE: An event during which symptoms of an HAE were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose concentration \<70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Asymptomatic: An event not accompanied by typical symptoms of an HAE, but a plasma/blood glucose value of \<70 mg/dL was reported.
Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Up to week 28	Vital signs included blood pressure and pulse rate and were measured with the participants in a seated position after at least 5 minutes of rest for the participant. Criteria for abnormalities included: Systolic Blood Pressure (millimeter of mercury \[mmHg\]): value more than (\>) 200 and value less than (\<) 90; Diastolic blood pressure: value \> 100 and \< 40; Pulse rate: (beats per minute \[BPM\]): value \< 40 and \> 110.
Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Up to week 28	Vital signs included blood pressure and pulse rate and were measured with the participants in a seated position after at least 5 minutes of rest for the participant. Criteria for abnormalities included: Systolic blood pressure (mmHg): value \> 200 and value \< 90; Diastolic blood pressure: value \> 100 and \< 40; Pulse rate: (BPM): value \< 40 and \> 110.
Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Up to week 28	Hematology: platelets (10\^9/L)\< 0.5\lower limit of normal (LLN); leukocytes\< 0.6\LLN and \>1.5\upper limit of normal (ULN); lymphocytes and neutrophils \<0.8\LLN and \>1.2\ULN; basophils, eosinophils, monocytes:\>1.2\ULN; prothrombin time (sec) \>1.1\ULN; prothrombin international normalized ratio \>1.1\ULN; clinical chemistry: bilirubin (mg/dL), indirect bilirubin:\>1.5\ULN; aspartate and alanine aminotransferase, gamma glutamyl transferase (U/L):\>3.0\ULN; urea nitrogen and creatinine (mg/dL)\>1.3\* ULN;HDL cholesterol (mg/dL)\<0.8\LLN; LDL (mg/dL)\>1.2\ULN, Triglycerides (mg/dL):\>1.3\ULN; Potassium (milliequivalents per liter) \< 0.9\LLN and \> 1.1\* ULN; calcium (mg/dL)\< 0.9\LLN, Thyroxine (nanograms/dL\<0.8\LLN and \>1.2\ULN, HbA1C (%)\>1.3\ULN; Amylase, Lipase (U/L) and Glucose -Fasting (mg/dL)\>1.5\*ULN; urinalysis: pH\> 8; urine glucose, ketones, protein, hemoglobin, nitrite and leukocyte esterase\>=1. Number of participants with abnormalities in any of the laboratory parameters is reported.
Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)	Up to week 28	Hematology: platelets (10\^9/L)\< 0.5\* LLN; leukocytes\< 0.6\LLN and \>1.5\ULN; lymphocytes and neutrophils \<0.8\LLN and \>1.2\ULN; basophils, eosinophils, monocytes:\>1.2\ULN; prothrombin time (sec) \>1.1\ULN; prothrombin international normalized ratio \>1.1\ULN; clinical chemistry: bilirubin (mg/dL), indirect bilirubin:\>1.5\ULN; aspartate and alanine aminotransferase, gamma glutamyl transferase (U/L):\>3.0\ULN; urea nitrogen and creatinine (mg/dL)\>1.3\ ULN;HDL cholesterol (mg/dL)\<0.8\LLN; LDL (mg/dL)\>1.2\ULN, Triglycerides (mg/dL):\>1.3\ULN; Potassium (milliequivalents per liter) \< 0.9\LLN and \> 1.1\* ULN; calcium (mg/dL)\< 0.9\LLN, Thyroxine (nanograms/dL\<0.8\LLN and \>1.2\ULN, HbA1C (%)\>1.3\ULN; Amylase, Lipase (U/L) and Glucose -Fasting (mg/dL)\>1.5\*ULN; urinalysis: pH\> 8; urine glucose, ketones, protein, hemoglobin, nitrite and leukocyte esterase\>=1. Number of participants with abnormalities in any of the laboratory parameters is reported.
Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Up to week 28	Standard 12-lead ECGs were performed after the participant had rested quietly for more than 10 minutes in a supine position utilizing an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QT interval corrected using Fridericia's formula (QTcF), and QRS complex. ECG abnormalities were categorized as: PR interval (milliseconds \[msec\]), Value \>= 300; percent change (%Chg) greater than equal (\>=) 25/50%. QRS duration (msec): Value \>= 140 and %Chg \>= 50%. QT interval (msec): Value \> 500; QTCF interval (msec): 450 \< Value \<= 480, 480 \< Value \<= 500, Value \> 500; 30 \<= Change (Chg) \<= 60; Chg \> 60.
Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	Up to week 28	Standard 12-lead ECGs were performed after the participant had rested quietly for more than 10 minutes in a supine position utilizing an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF, and QRS complex. ECG abnormalities were categorized as: PR interval msec, Value \>= 300; percentage change (%Chg) \>= 25/50%. QRS duration (msec): Value \>= 140 and %Chg \>= 50%. QT interval (msec): Value \> 500; QTCF interval (msec): 450 \< Value \<= 480, 480 \< Value \<= 500, Value \> 500; 30 \<= Change (Chg) \<= 60; Chg \> 60.
Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline (result closest prior to dosing on Day 1), anytime post-baseline (Up to Week 28)	C-SSRS is an interview-based rating scale to assess suicidal ideation and suicidal behavior and had a binary response (yes/no). C-SSRS data was mapped to C-CASA per Guidance for Industry: Suicidal Ideation and Behavior: Prospective Assessment of Occurrence in Clinical Trials. A participant was said to have suicidal behavior in case of any of following events: 1) completed suicide; 2) suicide attempt; or 3) preparatory acts toward imminent suicidal behavior. A participant showed suicidal ideation if they responded 'yes' to any of the 5 questions, 'Wish to be dead; Non-Specific Active Suicidal Thoughts Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent. The participant was said to exhibit Self-injurious behavior, no suicidal intent if they responded as Yes to 'Has participant engaged in Non-suicidal Self-Injurious Behavior
Percentage of Participants Who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)	Baseline (result closest prior to dosing on Day 1), Week 32	—
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)	Baseline (result closest prior to dosing on Day 1), Week 32	—
Percent Change From Baseline in Body Weight at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)	Baseline (result closest prior to dosing on Day 1), Week 32	Body weight was measured using a calibrated weighing scale.
Placebo-adjusted, Change From Baseline in HbA1C in the Rybelsus Arm at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)	Baseline (result closest prior to dosing on Day 1), Week 32	This outcome measure was planned to be analyzed only for rybelsus arm and placebo arm as pre-specified in the protocol.
Percentage of Participants Achieving >=5%, >=10%, and >=15% Body Weight Loss at Week 32 Relative to Baseline: Cohort 2 (Obesity)	Baseline (result closest prior to dosing on Day 1), Week 32	—
Absolute Change From Baseline in Waist Circumference at Week 32: Cohort 2 (Obesity)	Baseline (result closest prior to dosing on Day 1), Week 32	Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch \[2.54 centimeter {cm}\] above the navel). It was measured by using an anthropometric tape (stretch-resistant).
Absolute Change From Baseline in Waist-to-hip Ratio at Week 32: Cohort 2 (Obesity)	Baseline (result closest prior to dosing on Day 1), Week 32	The hip circumference was defined as the circumference around the widest portion of the buttocks. Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch \[2.54 cm\] above the navel). The measurements were performed using an anthropometric tape (stretch-resistant).
Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 32: Cohort 2 (Obesity)	Baseline (result closest prior to dosing on Day 1), Week 32	HOMA-IR was calculated as: fasting plasma insulin (\[FPI\]\(FPG)/405 and measured in terms of mg/dL\ (milliunits per liter).
Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)	From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of treatment but before the last dose plus lag time.
Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)	From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of treatment but before the last dose plus lag time.
Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)	From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)	SAE defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; other important medical events.
Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)	From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)	SAE defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; other important medical events.
Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)	\\ An AE was any untoward medical occurrence in a participants or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs leading to permanent discontinuation from study were those with an AE record indicating the AE caused permanent discontinuation from the study. AEs leading to permanent discontinuation from study treatment were those AEs with an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study.
Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)	An AE was any untoward medical occurrence in a participants or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs leading to permanent discontinuation from study were those with an AE record indicating the AE caused permanent discontinuation from the study. AEs leading to permanent discontinuation from study treatment were those AEs with an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study.

Other

Measure	Time frame	Description
Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16	Body weight was measured using a calibrated weighing scale.
Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus Arm Versus Placebo Arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16	Analysis was performed using MMRM model including treatment, gender strata and time as fixed effects, baseline\time interaction, time\treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect. This outcome measure was planned to be analyzed only for rybelsus arm and placebo arm as pre-specified in the protocol.
Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], Week 12, 24	Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch \[2.54 cm\] above the navel). It was measured by using an anthropometric tape (stretch-resistant).
Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], week 12, 24	The hip circumference was defined as the circumference around the widest portion of the buttocks. Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch \[2.54 cm\] above the navel). The measurements were performed using an anthropometric tape (stretch-resistant).
Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16	HOMA-IR was calculated as: (\[FPI\]\(FPG)/405 in terms of Mg/dL\ (milliunits per liter).
Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16	HOMA-S was calculated as (22.5/\[FPI\]\FPG)) \100 and measured in terms of. percentage sensitivity.
Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 20	Body weight was measured using a calibrated weighing scale. Analysis was performed using MMRM model including treatment, gender strata and time as fixed effects, baseline\time interaction, time\treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16	—
Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16	Analysis was performed using mixed model repeated measures (MMRM) model including treatment, gender strata and time as fixed effects, baseline\time interaction, time\treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect.

Countries

Bulgaria, Canada, Czechia, Hungary, Japan, Poland, Puerto Rico, United States

Participant flow

Recruitment details

This study had 2 cohorts: Cohort 1 included participants with type 2 diabetes mellitus (T2DM) on a background therapy of metformin. Cohort 2 included participants with obesity but without T2DM.

Pre-assignment details

A total of 902 participants were randomized in this study of which 1 participant did not receive treatment. The study was terminated based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as this Phase 2 study.

Participants by arm

Arm	Count
Placebo (T2DM) Participants randomized to receive a single dose of PF-07081532-matching placebo QD orally.	75
PF-07081532 20mg (T2DM) Participants randomized to receive PF-07081532 20 mg QD orally.	73
PF-07081532 40mg (T2DM) Participants randomized to receive PF-07081532 20 mg QD orally for 4 weeks, followed by 40 mg QD orally.	72
PF-07081532 80mg (T2DM) Participants randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks, followed by PF-07081532 80 mg QD orally.	73
PF-07081532 160mg (T2DM) Participants randomized to receive PF-07081532 20 mg QD 40 mg QD, 60 mg QD, 80 mg QD and 120 mg QD orally for 4 weeks, followed by PF-07081532 160 mg QD orally.	72
PF-07081532 260mg (T2DM) Participants randomized to receive PF-07081532 20 mg QD, 40 mg QD, 80 mg QD, 140 mg QD and 200 mg QD orally for 4 weeks, followed by PF-07081532 260 mg QD orally.	74
Rybelsus 14mg (T2DM) Participants randomized to receive Rybelsus 3 mg QD and 7 mg QD each for 4 weeks followed by 14 mg QD.	73
Placebo (Obesity) Participants randomized to receive a single dose of PF-07081532-matching placebo QD orally.	64
PF-07081532 80mg (Obesity) Participants randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD orally for 4 weeks, followed by PF-07081532 80 mg QD orally.	66
PF-07081532 140mg (Obesity) Participants randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 80 mg QD,120 mg QD orally for 4 weeks each followed by PF-07081532 140 mg QD orally.	64
PF-07081532 200mg (Obesity,5 Steps) Participants randomized to receive PF-07081532 20 mg QD, 40 mg QD and 60 mg QD, 100 mg QD,160 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.	65
PF-07081532 200mg (Obesity,4 Steps) Participants randomized to receive PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD orally for 4 weeks each followed by PF-07081532 200 mg QD orally.	66
PF-07081532 260mg (Obesity) Participants randomized to receive PF-07081532 20 mg QD, 40 mg QD and 80 mg QD, 140 mg QD, 200 mg QD orally for 4 weeks each followed by PF-07081532 260 mg QD orally.	64
Total	901

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012
Follow up	Death	1	0	0	0	0	0	0	0	0	0	0	0	0
Follow up	Lost to Follow-up	0	0	0	1	1	2	1	1	3	2	2	4	4
Follow up	Withdrawal by Subject	2	0	0	0	1	0	1	4	2	3	3	1	3
Treatment Phase	Adverse Event	0	3	11	10	5	17	5	5	12	20	15	24	23
Treatment Phase	Death	1	0	0	0	0	0	0	0	0	0	0	0	0
Treatment Phase	Lost to Follow-up	0	0	0	1	1	1	0	1	2	2	1	4	3
Treatment Phase	Other	0	0	0	2	1	2	1	2	2	1	0	0	3
Treatment Phase	Physician Decision	0	0	0	0	0	0	0	0	0	0	0	1	0
Treatment Phase	Pregnancy	0	0	0	0	0	0	0	0	0	1	0	0	0
Treatment Phase	Randomized not treated	0	0	0	0	1	0	0	0	0	0	0	0	0
Treatment Phase	Study terminated by sponsor	70	70	61	59	63	53	66	48	47	37	44	36	32
Treatment Phase	Treatment with restricted medication needed	2	0	0	0	0	1	0	0	0	0	0	0	0
Treatment Phase	Withdrawal by Subject	2	0	0	1	2	0	1	8	3	3	5	1	3

Baseline characteristics

Characteristic	Placebo (T2DM)	Total	PF-07081532 260mg (Obesity)	PF-07081532 200mg (Obesity,4 Steps)	PF-07081532 200mg (Obesity,5 Steps)	PF-07081532 140mg (Obesity)	PF-07081532 80mg (Obesity)	Placebo (Obesity)	Rybelsus 14mg (T2DM)	PF-07081532 260mg (T2DM)	PF-07081532 160mg (T2DM)	PF-07081532 80mg (T2DM)	PF-07081532 40mg (T2DM)	PF-07081532 20mg (T2DM)
Age, Customized 18-44 years	6 Participants	171 Participants	23 Participants	21 Participants	25 Participants	24 Participants	25 Participants	17 Participants	5 Participants	6 Participants	4 Participants	4 Participants	3 Participants	8 Participants
Age, Customized 45-64 years	40 Participants	512 Participants	33 Participants	39 Participants	34 Participants	35 Participants	33 Participants	36 Participants	43 Participants	36 Participants	44 Participants	48 Participants	52 Participants	39 Participants
Age, Customized Less than (<) 18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Customized More than equal to (>=) 65 years	29 Participants	218 Participants	8 Participants	6 Participants	6 Participants	5 Participants	8 Participants	11 Participants	25 Participants	32 Participants	24 Participants	21 Participants	17 Participants	26 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	14 Participants	133 Participants	10 Participants	12 Participants	14 Participants	10 Participants	8 Participants	5 Participants	8 Participants	10 Participants	14 Participants	7 Participants	8 Participants	13 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	61 Participants	766 Participants	54 Participants	54 Participants	51 Participants	54 Participants	58 Participants	59 Participants	64 Participants	64 Participants	58 Participants	66 Participants	63 Participants	60 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	5 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	12 Participants	119 Participants	6 Participants	4 Participants	3 Participants	3 Participants	3 Participants	4 Participants	11 Participants	14 Participants	13 Participants	15 Participants	17 Participants	14 Participants
Race (NIH/OMB) Black or African American	4 Participants	69 Participants	4 Participants	5 Participants	6 Participants	15 Participants	6 Participants	4 Participants	5 Participants	5 Participants	5 Participants	4 Participants	4 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	2 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	58 Participants	703 Participants	52 Participants	55 Participants	56 Participants	44 Participants	56 Participants	55 Participants	57 Participants	54 Participants	54 Participants	54 Participants	51 Participants	57 Participants
Sex: Female, Male Female	42 Participants	469 Participants	40 Participants	42 Participants	36 Participants	45 Participants	38 Participants	36 Participants	36 Participants	31 Participants	33 Participants	31 Participants	29 Participants	30 Participants
Sex: Female, Male Male	33 Participants	432 Participants	24 Participants	24 Participants	29 Participants	19 Participants	28 Participants	28 Participants	37 Participants	43 Participants	39 Participants	42 Participants	43 Participants	43 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk
deaths Total, all-cause mortality	1 / 75	0 / 73	0 / 72	0 / 73	0 / 72	0 / 74	0 / 73	0 / 64	0 / 66	0 / 64	0 / 65	0 / 66	0 / 64
other Total, other adverse events	23 / 75	31 / 73	46 / 72	37 / 73	41 / 72	51 / 74	32 / 73	42 / 64	50 / 66	48 / 64	55 / 65	59 / 66	53 / 64
serious Total, serious adverse events	1 / 75	0 / 73	3 / 72	3 / 73	1 / 72	2 / 74	1 / 73	1 / 64	2 / 66	2 / 64	1 / 65	2 / 66	2 / 64

Outcome results

Primary

Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Primary

Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 32: Cohort 2 (Obesity)

Body weight was measured using a calibrated weighing scale.

Time frame: Baseline (result closest prior to dosing on Day 1), week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Secondary

Absolute Change From Baseline in Waist Circumference at Week 32: Cohort 2 (Obesity)

Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch \[2.54 centimeter {cm}\] above the navel). It was measured by using an anthropometric tape (stretch-resistant).

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Secondary

Absolute Change From Baseline in Waist-to-hip Ratio at Week 32: Cohort 2 (Obesity)

The hip circumference was defined as the circumference around the widest portion of the buttocks. Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch \[2.54 cm\] above the navel). The measurements were performed using an anthropometric tape (stretch-resistant).

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Secondary

Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 32: Cohort 2 (Obesity)

HOMA-IR was calculated as: fasting plasma insulin (\[FPI\]\*(FPG)/405 and measured in terms of mg/dL\* (milliunits per liter).

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Secondary

Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 32: Cohort 2 (Obesity)

HOMA-S was calculated as (22.5/\[FPI\] \* FPG) \*100 and measured in terms of percentage sensitivity.

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Secondary

Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only

C-SSRS is an interview-based rating scale to assess suicidal ideation and suicidal behavior and had a binary response (yes/no). C-SSRS data was mapped to C-CASA per Guidance for Industry: Suicidal Ideation and Behavior: Prospective Assessment of Occurrence in Clinical Trials. A participant was said to have suicidal behavior in case of any of following events: 1) completed suicide; 2) suicide attempt; or 3) preparatory acts toward imminent suicidal behavior. A participant showed suicidal ideation if they responded 'yes' to any of the 5 questions, 'Wish to be dead; Non-Specific Active Suicidal Thoughts Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent. The participant was said to exhibit Self-injurious behavior, no suicidal intent if they responded as Yes to 'Has participant engaged in Non-suicidal Self-Injurious Behavior

Time frame: Baseline (result closest prior to dosing on Day 1), anytime post-baseline (Up to Week 28)

Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received. This outcome measure was planned to be assessed in Cohort 2 only.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <2> Suicide attempt	0 Participants
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <1> Completed suicide	0 Participants
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <4> Suicidal ideation	0 Participants
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <3> Preparatory acts towards imminent suicidal behavior	1 Participants
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <2> Suicide attempt	0 Participants
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <1> Completed suicide	0 Participants
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <7> Self-injurious behavior, no suicidal intent	1 Participants
Placebo (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <4> Suicidal ideation	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <1> Completed suicide	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <2> Suicide attempt	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <1> Completed suicide	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <2> Suicide attempt	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <4> Suicidal ideation	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <4> Suicidal ideation	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <1> Completed suicide	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <4> Suicidal ideation	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <4> Suicidal ideation	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <2> Suicide attempt	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <1> Completed suicide	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <2> Suicide attempt	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <1> Completed suicide	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <2> Suicide attempt	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <4> Suicidal ideation	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <1> Completed suicide	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <4> Suicidal ideation	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <2> Suicide attempt	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <1> Completed suicide	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <4> Suicidal ideation	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <1> Completed suicide	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <4> Suicidal ideation	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <2> Suicide attempt	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <2> Suicide attempt	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <4> Suicidal ideation	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <2> Suicide attempt	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <3> Preparatory acts towards imminent suicidal behavior	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <2> Suicide attempt	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <1> Completed suicide	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <4> Suicidal ideation	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Post-Baseline: <1> Completed suicide	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only	Baseline: <7> Self-injurious behavior, no suicidal intent	0 Participants

Secondary

Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)

\\ An AE was any untoward medical occurrence in a participants or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs leading to permanent discontinuation from study were those with an AE record indicating the AE caused permanent discontinuation from the study. AEs leading to permanent discontinuation from study treatment were those AEs with an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study.

Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Discontinuations from study due to TEAEs	1 Participants
Placebo (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Permanent discontinuations from any study intervention due to TEAEs	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Discontinuations from study due to TEAEs	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Permanent discontinuations from any study intervention due to TEAEs	3 Participants
PF-07081532 40mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Discontinuations from study due to TEAEs	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Permanent discontinuations from any study intervention due to TEAEs	11 Participants
PF-07081532 80mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Discontinuations from study due to TEAEs	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Permanent discontinuations from any study intervention due to TEAEs	10 Participants
PF-07081532 160mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Discontinuations from study due to TEAEs	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Permanent discontinuations from any study intervention due to TEAEs	5 Participants
PF-07081532 260mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Discontinuations from study due to TEAEs	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Permanent discontinuations from any study intervention due to TEAEs	17 Participants
Rybelsus 14mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Discontinuations from study due to TEAEs	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)	Permanent discontinuations from any study intervention due to TEAEs	5 Participants

Secondary

Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)

An AE was any untoward medical occurrence in a participants or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs leading to permanent discontinuation from study were those with an AE record indicating the AE caused permanent discontinuation from the study. AEs leading to permanent discontinuation from study treatment were those AEs with an AE record indicating that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study.

Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Discontinuations from study due to TEAEs	0 Participants
Placebo (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Permanent discontinuations from any study intervention due to TEAEs	5 Participants
PF-07081532 20mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Discontinuations from study due to TEAEs	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Permanent discontinuations from any study intervention due to TEAEs	12 Participants
PF-07081532 40mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Discontinuations from study due to TEAEs	1 Participants
PF-07081532 40mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Permanent discontinuations from any study intervention due to TEAEs	19 Participants
PF-07081532 80mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Discontinuations from study due to TEAEs	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Permanent discontinuations from any study intervention due to TEAEs	15 Participants
PF-07081532 160mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Discontinuations from study due to TEAEs	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Permanent discontinuations from any study intervention due to TEAEs	24 Participants
PF-07081532 260mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Discontinuations from study due to TEAEs	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)	Permanent discontinuations from any study intervention due to TEAEs	22 Participants

Secondary

Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Hematology: platelets (10\^9/L)\< 0.5\*lower limit of normal (LLN); leukocytes\< 0.6\*LLN and \>1.5\*upper limit of normal (ULN); lymphocytes and neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes:\>1.2\*ULN; prothrombin time (sec) \>1.1\*ULN; prothrombin international normalized ratio \>1.1\*ULN; clinical chemistry: bilirubin (mg/dL), indirect bilirubin:\>1.5\*ULN; aspartate and alanine aminotransferase, gamma glutamyl transferase (U/L):\>3.0\*ULN; urea nitrogen and creatinine (mg/dL)\>1.3\* ULN;HDL cholesterol (mg/dL)\<0.8\*LLN; LDL (mg/dL)\>1.2\*ULN, Triglycerides (mg/dL):\>1.3\*ULN; Potassium (milliequivalents per liter) \< 0.9\*LLN and \> 1.1\* ULN; calcium (mg/dL)\< 0.9\*LLN, Thyroxine (nanograms/dL\<0.8\*LLN and \>1.2\*ULN, HbA1C (%)\>1.3\*ULN; Amylase, Lipase (U/L) and Glucose -Fasting (mg/dL)\>1.5\*ULN; urinalysis: pH\> 8; urine glucose, ketones, protein, hemoglobin, nitrite and leukocyte esterase\>=1. Number of participants with abnormalities in any of the laboratory parameters is reported.

Time frame: Up to week 28

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	67 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	64 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	57 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	57 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	61 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	59 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	64 Participants

Secondary

Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)

Hematology: platelets (10\^9/L)\< 0.5\* LLN; leukocytes\< 0.6\*LLN and \>1.5\*ULN; lymphocytes and neutrophils \<0.8\*LLN and \>1.2\*ULN; basophils, eosinophils, monocytes:\>1.2\*ULN; prothrombin time (sec) \>1.1\*ULN; prothrombin international normalized ratio \>1.1\*ULN; clinical chemistry: bilirubin (mg/dL), indirect bilirubin:\>1.5\*ULN; aspartate and alanine aminotransferase, gamma glutamyl transferase (U/L):\>3.0\*ULN; urea nitrogen and creatinine (mg/dL)\>1.3\* ULN;HDL cholesterol (mg/dL)\<0.8\*LLN; LDL (mg/dL)\>1.2\*ULN, Triglycerides (mg/dL):\>1.3\*ULN; Potassium (milliequivalents per liter) \< 0.9\*LLN and \> 1.1\* ULN; calcium (mg/dL)\< 0.9\*LLN, Thyroxine (nanograms/dL\<0.8\*LLN and \>1.2\*ULN, HbA1C (%)\>1.3\*ULN; Amylase, Lipase (U/L) and Glucose -Fasting (mg/dL)\>1.5\*ULN; urinalysis: pH\> 8; urine glucose, ketones, protein, hemoglobin, nitrite and leukocyte esterase\>=1. Number of participants with abnormalities in any of the laboratory parameters is reported.

Time frame: Up to week 28

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)	36 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)	31 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)	40 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)	40 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)	48 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)	36 Participants

Secondary

Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Standard 12-lead ECGs were performed after the participant had rested quietly for more than 10 minutes in a supine position utilizing an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QT interval corrected using Fridericia's formula (QTcF), and QRS complex. ECG abnormalities were categorized as: PR interval (milliseconds \[msec\]), Value \>= 300; percent change (%Chg) greater than equal (\>=) 25/50%. QRS duration (msec): Value \>= 140 and %Chg \>= 50%. QT interval (msec): Value \> 500; QTCF interval (msec): 450 \< Value \<= 480, 480 \< Value \<= 500, Value \> 500; 30 \<= Change (Chg) \<= 60; Chg \> 60.

Time frame: Up to week 28

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 450 < Value <=480	5 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) value >=300	1 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) value >=140	1 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) %Chg >=50%	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	3 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 450 < Value <=480	7 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	7 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) value >=300	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) value >=140	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) value >=300	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) value >=140	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	5 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 450 < Value <=480	3 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	4 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) value >=140	1 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 450 < Value <=480	5 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) value >=300	1 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) value >=140	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) value >=300	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 450 < Value <=480	5 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	3 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) value >=140	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) value >=300	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 450 < Value <=480	2 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	10 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 480 < Value <=500	1 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) value >=140	3 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	8 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QRS duration, (MSEC) %Chg >=50%	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QT interval, single beat (MSEC) value > 500	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) 450 < Value <=480	5 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	PR Interval, (MSEC) value >=300	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	QTCF interval, single beat (MSEC) Value > 500	0 Participants

Secondary

Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)

Standard 12-lead ECGs were performed after the participant had rested quietly for more than 10 minutes in a supine position utilizing an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF, and QRS complex. ECG abnormalities were categorized as: PR interval msec, Value \>= 300; percentage change (%Chg) \>= 25/50%. QRS duration (msec): Value \>= 140 and %Chg \>= 50%. QT interval (msec): Value \> 500; QTCF interval (msec): 450 \< Value \<= 480, 480 \< Value \<= 500, Value \> 500; 30 \<= Change (Chg) \<= 60; Chg \> 60.

Time frame: Up to week 28

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) %Chg >=50%	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) value >=140	1 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	3 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) value >=300	0 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 450 < Value <=480	9 Participants
Placebo (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) value >=300	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) value >=140	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 450 < Value <=480	3 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	8 Participants
PF-07081532 20mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 450 < Value <=480	4 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	4 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) value >=140	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) value >=300	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	4 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) value >=140	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QT interval, single beat (MSEC) value > 500	1 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) value >=300	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 450 < Value <=480	2 Participants
PF-07081532 80mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 450 < Value <=480	4 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) value >=300	1 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	4 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) value >=140	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) %Chg >= 25/50%	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QT interval, single beat (MSEC) value > 500	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 30 <= Chg <= 60	3 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 450 < Value <=480	7 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) value >=300	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) 480 < Value <=500	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Value > 500	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QTCF interval, single beat (MSEC) Chg > 60	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) value >=140	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	QRS duration, (MSEC) %Chg >=50%	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)	PR Interval, (MSEC) %Chg >= 25/50%	0 Participants

Secondary

Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)

Glucose values were monitored using glucometer. Hypoglycemia =plasma/blood glucose value of \<70 mg/dL (3.9 mmol/L). Severe HAE: Participant was unable to treat him/herself due to neurological impairment (not age) and required assistance of another person, at least one neurological symptom of memory loss, confusion, uncontrolled behavior etc. Either documented blood glucose\<=54 mg/dL (2.7 mmol/L). Documented symptomatic: An event during which symptoms of HAE were accompanied with plasma/blood glucose \<70 mg/dL u and prompt resolution with food intake, SC glucagon, or IV glucose. Probable symptomatic HAE: An event during which symptoms of an HAE were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose concentration \<70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Asymptomatic: An event not accompanied by typical symptoms of an HAE, but a plasma/blood glucose value of \<70 mg/dL was reported.

Time frame: Up to week 28

Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Here, 'Overall Number of Participants Analyzed' signifies total number of participants with at least one dose of the given titration dose level after pooling of data across each titration dose.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
Placebo (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
Placebo (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
Placebo (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
PF-07081532 200mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
PF-07081532 200mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 200mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 200mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 260 mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 260 mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 260 mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants
PF-07081532 260 mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	1 Participants
Rybelsus 3mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Documented Symptomatic Hypoglycemia	0 Participants
Rybelsus 3mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Probable Symptomatic Hypoglycemia	0 Participants
Rybelsus 3mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Asymptomatic Hypoglycemia	0 Participants
Rybelsus 3mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)	Severe Hypoglycemia	0 Participants

Secondary

Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)

Glucose values were monitored using glucometer. Hypoglycemia =plasma/blood glucose value of \<70 mg/dL (3.9 millimoles per liter \[mmol/L\]). Severe HAE: Participant was unable to treat him/herself due to neurological impairment (not age) and required assistance of another person, at least one neurological symptom of memory loss, confusion, uncontrolled behavior etc. Either documented blood glucose\<=54 mg/dL (2.7 mmol/L). Documented symptomatic: An event during which symptoms of HAE were accompanied with plasma/blood glucose \<70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Probable symptomatic HAE: An event during which symptoms of an HAE were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose concentration \<70 mg/dL and prompt resolution with food intake, SC glucagon, or IV glucose. Asymptomatic: An event not accompanied by typical symptoms of an HAE, but a plasma/blood glucose value of \<70 mg/dL was reported.

Time frame: Up to week 28

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	1 Participants
Placebo (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	0 Participants
Placebo (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
Placebo (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	1 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	1 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	1 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	2 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	1 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	1 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	1 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	1 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
PF-07081532 200mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 200mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
PF-07081532 200mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 200mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 260 mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	0 Participants
PF-07081532 260 mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	0 Participants
PF-07081532 260 mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
PF-07081532 260 mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
Rybelsus 3mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	0 Participants
Rybelsus 3mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
Rybelsus 3mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	1 Participants
Rybelsus 3mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	2 Participants
Rybelsus 7mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	1 Participants
Rybelsus 7mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants
Rybelsus 7mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	2 Participants
Rybelsus 7mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Documented Symptomatic Hypoglycemia	1 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Probable Symptomatic Hypoglycemia	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Asymptomatic Hypoglycemia	2 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)	Severe Hypoglycemia	0 Participants

Secondary

Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)

SAE defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic; other important medical events.

Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)	1 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)	3 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)	3 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)	2 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)	1 Participants

Secondary

Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)

Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)	1 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)	2 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)	2 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)	1 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)	2 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)	2 Participants

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)

An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of treatment but before the last dose plus lag time.

Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)	35 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)	37 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)	50 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)	44 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)	45 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)	56 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)	36 Participants

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any AEs that occurred on or after the first dose of treatment but before the last dose plus lag time.

Time frame: From start of treatment up to minimum of 28 days after last dose of treatment administration (maximum up to Week 28)

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)	44 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)	54 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)	50 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)	56 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)	60 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)	53 Participants

Secondary

Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Vital signs included blood pressure and pulse rate and were measured with the participants in a seated position after at least 5 minutes of rest for the participant. Criteria for abnormalities included: Systolic Blood Pressure (millimeter of mercury \[mmHg\]): value more than (\>) 200 and value less than (\<) 90; Diastolic blood pressure: value \> 100 and \< 40; Pulse rate: (beats per minute \[BPM\]): value \< 40 and \> 110.

Time frame: Up to week 28

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value >110 bpm	0 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	0 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value <90 mmHg	0 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value <90 mmHg	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	4 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value >110 bpm	1 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value >110 bpm	1 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	2 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value <90 mmHg	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value <90 mmHg	1 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	2 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value >110 bpm	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	2 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value >110 bpm	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value <90 mmHg	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value <90 mmHg	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value >110 bpm	1 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value >110 bpm	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	2 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Pulse Rate (bpm) Value <40 bpm	0 Participants
Rybelsus 14mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)	Systolic Blood Pressure (mmHg) Value <90 mmHg	0 Participants

Secondary

Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)

Vital signs included blood pressure and pulse rate and were measured with the participants in a seated position after at least 5 minutes of rest for the participant. Criteria for abnormalities included: Systolic blood pressure (mmHg): value \> 200 and value \< 90; Diastolic blood pressure: value \> 100 and \< 40; Pulse rate: (BPM): value \< 40 and \> 110.

Time frame: Up to week 28

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	4 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value >110 bpm	0 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value <40 bpm	0 Participants
Placebo (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value <90 mmHg	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value <90 mmHg	3 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	4 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value >110 bpm	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 20mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	4 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value <90 mmHg	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 40mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value >110 bpm	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value <90 mmHg	2 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value >110 bpm	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	0 Participants
PF-07081532 80mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value <90 mmHg	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value >110 bpm	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value <40 bpm	0 Participants
PF-07081532 160mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	2 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value >110 bpm	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value <90 mmHg	1 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Systolic Blood Pressure (mmHg) Value >200 mmHg	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value <40 mmHg	0 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Diastolic Blood Pressure (mmHg) Value >100 mmHg	3 Participants
PF-07081532 260mg (T2DM)	Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)	Pulse Rate (bpm) Value <40 bpm	0 Participants

Secondary

Percentage of Participants Achieving >=5%, >=10%, and >=15% Body Weight Loss at Week 32 Relative to Baseline: Cohort 2 (Obesity)

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Secondary

Percentage of Participants Who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Secondary

Percent Change From Baseline in Body Weight at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Body weight was measured using a calibrated weighing scale.

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Secondary

Placebo-adjusted, Change From Baseline in HbA1C in the Rybelsus Arm at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

This outcome measure was planned to be analyzed only for rybelsus arm and placebo arm as pre-specified in the protocol.

Time frame: Baseline (result closest prior to dosing on Day 1), Week 32

Population: Data was not collected for this outcome measure as the study was terminated prior to any participant reaching Week 32.

Other Pre-specified

Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)

Waist circumference was measured at midpoint, between lower margin of last palpable rib and top of iliac crest (approximately 1 inch \[2.54 cm\] above the navel). It was measured by using an anthropometric tape (stretch-resistant).

Time frame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], Week 12, 24

Population: Evaluable set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to randomized intervention. Here Number Analyzed refers to the number of participants evaluable for the specified rows.

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 12	-2.702 Centimeter	Standard Deviation 4.1726
Placebo (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 24	-4.233 Centimeter	Standard Deviation 5.3953
PF-07081532 20mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 12	-2.574 Centimeter	Standard Deviation 5.0872
PF-07081532 20mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 24	-5.147 Centimeter	Standard Deviation 4.1807
PF-07081532 40mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 24	-6.314 Centimeter	Standard Deviation 10.217
PF-07081532 40mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 12	-3.017 Centimeter	Standard Deviation 5.9117
PF-07081532 80mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 12	-3.559 Centimeter	Standard Deviation 6.5122
PF-07081532 80mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 24	-2.722 Centimeter	Standard Deviation 7.6706
PF-07081532 160mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 12	-2.191 Centimeter	Standard Deviation 5.2942
PF-07081532 160mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 24	-10.297 Centimeter	Standard Deviation 7.7652
PF-07081532 260mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 24	-6.450 Centimeter	Standard Deviation 4.2123
PF-07081532 260mg (T2DM)	Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)	Week 12	-1.079 Centimeter	Standard Deviation 4.671

Other Pre-specified

Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)

Time frame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], week 12, 24

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 12	-0.013 Ratio	Standard Deviation 0.0374
Placebo (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 24	-0.023 Ratio	Standard Deviation 0.0419
PF-07081532 20mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 12	-0.002 Ratio	Standard Deviation 0.0459
PF-07081532 20mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 24	-0.017 Ratio	Standard Deviation 0.025
PF-07081532 40mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 12	-0.006 Ratio	Standard Deviation 0.0578
PF-07081532 40mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 24	-0.032 Ratio	Standard Deviation 0.0588
PF-07081532 80mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 12	-0.010 Ratio	Standard Deviation 0.0683
PF-07081532 80mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 24	0.018 Ratio	Standard Deviation 0.0563
PF-07081532 160mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 12	-0.002 Ratio	Standard Deviation 0.0423
PF-07081532 160mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 24	-0.009 Ratio	Standard Deviation 0.0498
PF-07081532 260mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 12	0.015 Ratio	Standard Deviation 0.0557
PF-07081532 260mg (T2DM)	Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)	Week 24	-0.037 Ratio	Standard Deviation 0.0574

Other Pre-specified

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Time frame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16

Population: Evaluable set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to randomized intervention. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Placebo (T2DM)	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	160.70 Milligrams per deciliter	Standard Deviation 39.595
PF-07081532 20mg (T2DM)	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	135.59 Milligrams per deciliter	Standard Deviation 31.746
PF-07081532 40mg (T2DM)	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	127.00 Milligrams per deciliter	Standard Deviation 35.928
PF-07081532 80mg (T2DM)	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	132.19 Milligrams per deciliter	Standard Deviation 31.541
PF-07081532 160mg (T2DM)	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	127.65 Milligrams per deciliter	Standard Deviation 28.839
PF-07081532 260mg (T2DM)	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	125.07 Milligrams per deciliter	Standard Deviation 46.924
Rybelsus 14mg (T2DM)	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	130.06 Milligrams per deciliter	Standard Deviation 28.12

Other Pre-specified

Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)

HOMA-IR was calculated as: (\[FPI\]\*(FPG)/405 in terms of Mg/dL\* (milliunits per liter).

Time frame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16

Population: Evaluable set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to randomized intervention. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Placebo (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)	0.630 Milliunits per liter	Standard Deviation 2.1753
PF-07081532 20mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)	0.185 Milliunits per liter	Standard Deviation 2.0579
PF-07081532 40mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)	-0.121 Milliunits per liter	Standard Deviation 4.754
PF-07081532 80mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)	0.984 Milliunits per liter	Standard Deviation 3.909
PF-07081532 160mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)	-1.172 Milliunits per liter	Standard Deviation 2.736
PF-07081532 260mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)	-0.210 Milliunits per liter	Standard Deviation 1.1373

Other Pre-specified

Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)

HOMA-S was calculated as (22.5/\[FPI\]\*FPG)) \*100 and measured in terms of. percentage sensitivity.

Time frame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16

Population: Evaluable set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to randomized intervention. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Placebo (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)	-2.419 Percentage sensitivity	Standard Deviation 51.8526
PF-07081532 20mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)	1.594 Percentage sensitivity	Standard Deviation 24.1848
PF-07081532 40mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)	7.807 Percentage sensitivity	Standard Deviation 26.5041
PF-07081532 80mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)	-7.085 Percentage sensitivity	Standard Deviation 21.6406
PF-07081532 160mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)	3.497 Percentage sensitivity	Standard Deviation 68.257
PF-07081532 260mg (T2DM)	Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)	-2.045 Percentage sensitivity	Standard Deviation 28.8973

Other Pre-specified

Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Body weight was measured using a calibrated weighing scale.

Time frame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16

Population: Evaluable set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to randomized intervention. Here, Number of Participants Analyzed refers to participants evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
Placebo (T2DM)	Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	93.164 Percent change	Standard Deviation 22.0659
PF-07081532 20mg (T2DM)	Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	86.251 Percent change	Standard Deviation 17.3464
PF-07081532 40mg (T2DM)	Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	91.556 Percent change	Standard Deviation 23.4071
PF-07081532 80mg (T2DM)	Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	92.979 Percent change	Standard Deviation 24.5045
PF-07081532 160mg (T2DM)	Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	85.564 Percent change	Standard Deviation 17.9582
PF-07081532 260mg (T2DM)	Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	87.658 Percent change	Standard Deviation 21.695
Rybelsus 14mg (T2DM)	Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	91.799 Percent change	Standard Deviation 20.4605

Other Pre-specified

Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Analysis was performed using mixed model repeated measures (MMRM) model including treatment, gender strata and time as fixed effects, baseline\*time interaction, time\*treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect.

Time frame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16

Population: Evaluable set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to randomized intervention. Here, Overall Number of Participants Analyzed refers to participants evaluable for this outcome measure.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo (T2DM)	Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	-0.07 Percentage of HbA1c	Standard Error 0.109
PF-07081532 20mg (T2DM)	Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	-1.03 Percentage of HbA1c	Standard Error 0.106
PF-07081532 40mg (T2DM)	Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	-1.37 Percentage of HbA1c	Standard Error 0.112
PF-07081532 80mg (T2DM)	Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	-1.44 Percentage of HbA1c	Standard Error 0.111
PF-07081532 160mg (T2DM)	Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	-1.34 Percentage of HbA1c	Standard Error 0.11
PF-07081532 260mg (T2DM)	Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	-1.36 Percentage of HbA1c	Standard Error 0.114
Rybelsus 14mg (T2DM)	Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	-0.94 Percentage of HbA1c	Standard Error 0.109

p-value: <0.000190% CI: [-1.2, -0.7]Mixed Models Analysis

p-value: <0.000190% CI: [-1.55, -1.04]Mixed Models Analysis

p-value: <0.000190% CI: [-1.62, -1.11]Mixed Models Analysis

p-value: <0.000190% CI: [-1.52, -1.01]Mixed Models Analysis

p-value: <0.000190% CI: [-1.55, -1.03]Mixed Models Analysis

p-value: <0.000190% CI: [-1.12, -0.61]Mixed Models Analysis

Other Pre-specified

Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus Arm Versus Placebo Arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Analysis was performed using MMRM model including treatment, gender strata and time as fixed effects, baseline\*time interaction, time\*treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect. This outcome measure was planned to be analyzed only for rybelsus arm and placebo arm as pre-specified in the protocol.

Time frame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 16

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo (T2DM)	Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus Arm Versus Placebo Arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	-0.94 Percentage of HbA1C	Standard Error 0.109
PF-07081532 20mg (T2DM)	Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus Arm Versus Placebo Arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)	-0.07 Percentage of HbA1C	Standard Error 0.109

p-value: <0.000190% CI: [-1.12, -0.61]Mixed Models Analysis

Other Pre-specified

Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)

Body weight was measured using a calibrated weighing scale. Analysis was performed using MMRM model including treatment, gender strata and time as fixed effects, baseline\*time interaction, time\*treatment interaction, and baseline as a covariate with time fitted as a repeated effect and participant as a random effect.

Time frame: Baseline [(Baseline is defined as the result closest prior to dosing at Visit 3 (Day 1)], at Week 20

Population: Evaluable set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to randomized intervention. Here, Overall Number of Participants Analyzed refers to participants evaluable for this outcome measure.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo (T2DM)	Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)	-1.84 Percent change	Standard Error 0.612
PF-07081532 20mg (T2DM)	Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)	-4.28 Percent change	Standard Error 0.623
PF-07081532 40mg (T2DM)	Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)	-6.21 Percent change	Standard Error 0.654
PF-07081532 80mg (T2DM)	Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)	-7.47 Percent change	Standard Error 0.628
PF-07081532 160mg (T2DM)	Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)	-6.88 Percent change	Standard Error 0.638
PF-07081532 260mg (T2DM)	Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)	-7.26 Percent change	Standard Error 0.664

p-value: 0.005590% CI: [-3.88, -1]Mixed Models Analysis

p-value: <0.000190% CI: [-5.84, -2.89]Mixed Models Analysis

p-value: <0.000190% CI: [-7.07, -4.18]Mixed Models Analysis

p-value: <0.000190% CI: [-6.5, -3.58]Mixed Models Analysis

p-value: <0.000190% CI: [-6.91, -3.93]Mixed Models Analysis

Source: ClinicalTrials.gov · Data processed: Feb 5, 2026

Trial to Learn About the Study Medicine (PF-07081532) and Rybelsus in People With Type 2 Diabetes and Separately PF-07081532 in People With Obesity

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Other

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 32: Cohort 2 (Obesity)

Absolute Change From Baseline in Waist Circumference at Week 32: Cohort 2 (Obesity)

Absolute Change From Baseline in Waist-to-hip Ratio at Week 32: Cohort 2 (Obesity)

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 32: Cohort 2 (Obesity)

Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 32: Cohort 2 (Obesity)

Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS) Category: Cohort 2 (Obesity) Only

Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 1 (Type 2 Diabetes Mellitus)

Number of Participants Reporting Adverse Events Leading to Permanent Discontinuation From Study Treatment and Study: Cohort 2 (Obesity)

Number of Participants With Clinical Laboratory Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Number of Participants With Clinical Laboratory Abnormalities: Cohort 2 (Obesity)

Number of Participants With ECG Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Number of Participants With ECG Abnormalities: Cohort 2 (Obesity)

Number of Participants With Hypoglycemic Adverse Events According to Titration Dose: Cohort 2 (Obesity)

Number of Participants With Hypoglycemic Adverse Events (HAE) According to Titration Dose: Cohort 1 (Type 2 Diabetes Mellitus)

Number of Participants With Serious Adverse Events (SAEs): Cohort 1 (Type 2 Diabetes Mellitus)

Number of Participants With Serious Adverse Events (SAEs): Cohort 2 (Obesity)

Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 1 (Type 2 Diabetes Mellitus)

Number of Participants With Treatment Emergent Adverse Events (TEAEs): Cohort 2 (Obesity)

Number of Participants With Vital Sign Abnormalities: Cohort 1 (Type 2 Diabetes Mellitus)

Number of Participants With Vital Sign Abnormalities: Cohort 2 (Obesity)

Percentage of Participants Achieving >=5%, >=10%, and >=15% Body Weight Loss at Week 32 Relative to Baseline: Cohort 2 (Obesity)

Percentage of Participants Who Achieved HbA1C <7% at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Percent Change From Baseline in Body Weight at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Placebo-adjusted, Change From Baseline in HbA1C in the Rybelsus Arm at Week 32: Cohort 1 (Type 2 Diabetes Mellitus)

Absolute Change From Baseline in Waist Circumference at Week 12 and 24: Cohort 2 (Obesity)

Absolute Change From Baseline in Waist-to-hip Ratio at Week 12 and Week 24: Cohort 2 (Obesity)

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Change From Baseline in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) at Week 16: Cohort 2 (Obesity)

Change From Baseline in Homeostatic Model Assessment for Insulin Sensitivity (HOMA-S) at Week 16: Cohort 2 (Obesity)

Percent Change From Baseline in Body Weight at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Placebo-adjusted, Change From Baseline in Percentage of Glycated Hemoglobin (HbA1c) at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Placebo-adjusted, Change From Baseline in Percentage of HbA1C in the Rybelsus Arm Versus Placebo Arm at Week 16: Cohort 1 (Type 2 Diabetes Mellitus)

Placebo-adjusted, Percent Change From Baseline in Body Weight at Week 20: Cohort 2 (Obesity)