Ertugliflozin and Sitagliptin Co-administration Factorial... | NCT02099110

NCT02099110

ID	Type	Description
MK-8835-005	Other Identifier	Merck, Sharp & Dohme
B1521019	Other Identifier	Pfizer
2013-003698-82	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Pfizer	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ertugliflozin 5 mg + sitagliptin 100 mg	Experimental	Ertugliflozin 5 mg + sitagliptin 100 mg, oral, once daily for 52 weeks	Drug: Matching Placebo to Ertugliflozin 10 mg Drug: Ertugliflozin 5 mg Drug: Sitagliptin 100 mg Drug: Metformin >= 1500 mg/day Biological: Insulin Glargine Rescue Medication Drug: Glimepiride Rescue Medication
Ertugliflozin 15 mg + sitagliptin 100 mg	Experimental	Ertugliflozin 15 mg + sitagliptin 100 mg, oral, once daily for 52 weeks	Drug: Ertugliflozin 5 mg Drug: Ertugliflozin 10 mg Drug: Sitagliptin 100 mg Drug: Metformin >= 1500 mg/day Biological: Insulin Glargine Rescue Medication Drug: Glimepiride Rescue Medication
Ertugliflozin 5 mg	Experimental	Ertugliflozin 5 mg, oral, once daily for 52 weeks	Drug: Matching Placebo to Ertugliflozin 10 mg Drug: Matching Placebo to sitagliptin 100 mg Drug: Ertugliflozin 5 mg Drug: Metformin >= 1500 mg/day Biological: Insulin Glargine Rescue Medication Drug: Glimepiride Rescue Medication
Ertugliflozin 15 mg	Experimental	Ertugliflozin, oral, once daily for 52 weeks	Drug: Matching Placebo to sitagliptin 100 mg

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Matching Placebo to Ertugliflozin 5 mg	Drug	Placebo to ertugliflozin 5 mg tablet, oral, once daily for 52 weeks during the double-blind treatment period	Sitagliptin 100 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in A1C at Week 26: Excluding Rescue Approach	A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.	Baseline and Week 26
Percentage of Participants Who Experienced an Adverse Event (AE): Including Rescue Approach	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Including rescue approach data analysis included data following the initiation of rescue therapy.	Up to 54 weeks
Percentage of Participants Who Discontinued Study Treatment Due to an AE: Including Rescue Approach	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Including rescue approach data analysis included data following the initiation of rescue therapy.	Up to 52 weeks

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Body Weight at Week 26: Excluding Rescue Approach	This change from baseline reflects the Week 26 body weight minus the Week 0 body weight. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.	Baseline and Week 26

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Type 2 diabetes mellitus as per American Diabetes Association guidelines
On metformin monotherapy (>=1500 mg/day) for >=8 weeks with a Visit 1/Screening A1C >=7.5% and <=11.0% (>=58 mmol/mol and <=97 mmol/mol) OR On metformin monotherapy (>=1500 mg/day) for <8 weeks with a Visit 1/Screening A1C >=7.5% and <=11.0% (>=58 mmol/mol and <=97 mmol/mol) OR On metformin monotherapy <1500 mg/day with a Visit 1/Screening A1C >=8.0% and <=11.5% (>=64 mmol/mol and <=102 mmol/mol)
Body mass index (BMI) >=18.0 kg/m^2
Male or female not of reproductive potential
Female of reproductive potential who agrees to remain abstinent from heterosexual activity or to use 2 acceptable combinations of contraception

Exclusion Criteria:

History of type 1 diabetes mellitus or ketoacidosis
History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant
A known hypersensitivity or intolerance to any sodium glucose co-transporter 2 (SGLT2) inhibitor or sitagliptin
Has been treated with any of the following agents within 12 weeks of study start or during the pre-randomization period: Insulin of any type (except for short-term use [i.e., <=7 days] during concomitant illness or other stress), other injectable anti-hyperglycemic agents (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other SGLT2 inhibitors, alpha glucosidase inhibitors or meglitinides, dipeptidyl-peptidase 4 inhibitor (DPP-4 inhibitor), sulfonylureas (SUs), bromocriptine (Cycloset™), colesevelam (Welchol™), any other antihyperglycemic agents (AHA) with the exception of the protocol-approved agents
Is on a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable prior to study start
Has undergone bariatric surgery within the past 12 months or >12 months and is not weight stable prior to study start
A history of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, or New York Heart Association (NYHA) functional class III-IV heart failure within 3 months of study start
Active, obstructive uropathy or indwelling urinary catheter
History of malignancy <=5 years prior to study start, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
A known history of human immunodeficiency virus (HIV)
A blood dyscrasia or any disorder causing hemolysis or unstable red blood cells, or a clinically important hematological disorder (e.g. aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
A medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
Any clinically significant malabsorption condition
Current treatment for hyperthyroidism
On thyroid replacement therapy and not on a stable dose for at least 6 weeks prior study start
On a previous clinical study with ertugliflozin
Estimated glomerular filtration rate (eGFR) (using the 4-variable Modification of Diet in Renal Disease Study Equation (MDRD) equation) <60 mL/min/1.73 m^2
Serum creatinine >= 1.3 mg/dL (115 µmol/L) for males and >= 1.2 mg/dL (106 µmol/L) for females
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times upper limit of normal
Hemoglobin <12 g/dL (120 g/L) for males and <11 g/dL (110 g/L) for females.
Participated in other studies involving investigational drug(s) 30 days prior to study start
Surgical procedure within 6 weeks prior to study start or major surgery planned during the trial
Positive urine pregnancy test
Pregnant or breast-feeding, or planning to conceive during the trial, including 14 days following the last dose of study medication
Planning to undergo hormonal therapy in preparation for egg donation during the trial, including 14 days following the last dose of study medication
Routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week or engages in binge drinking
Donated blood or blood products within 6 weeks of study start

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29266675	Result	Pratley RE, Eldor R, Raji A, Golm G, Huyck SB, Qiu Y, Sunga S, Johnson J, Terra SG, Mancuso JP, Engel SS, Lauring B. Ertugliflozin plus sitagliptin versus either individual agent over 52 weeks in patients with type 2 diabetes mellitus inadequately controlled with metformin: The VERTIS FACTORIAL randomized trial. Diabetes Obes Metab. 2018 May;20(5):1111-1120. doi: 10.1111/dom.13194. Epub 2018 Jan 25.
34213819

IPD Sharing Statement Module

Results Section

Participant Flow Module

ID	Title	Description
FG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks
FG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Drug: Ertugliflozin 5 mg

Drug: Ertugliflozin 10 mg

Drug: Metformin >= 1500 mg/day

Biological: Insulin Glargine Rescue Medication

Drug: Glimepiride Rescue Medication

The Baseline Analysis Population was the All-Participants-As-Treated population. One participant randomized to the Ertugliflozin 15 mg + Sitagliptin 100 mg arm did not receive study medication.

Arm/Group Information

ID	Title	Description
BG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks
BG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks
BG002	Sitagliptin 100 mg	Sitagliptin 100 mg, oral, once daily for 52 weeks
BG003	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 5 mg + sitagliptin 100 mg, oral, once daily for 52 weeks
BG004	Ertugliflozin 15 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + sitagliptin 100 mg, oral, once daily for 52 weeks
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG000250 BG001248 BG002247 BG003243 BG004244 BG0051232

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title	Denominators	Categories
	ParticipantsBG000250 ParticipantsBG001248 ParticipantsBG002247 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000250 ParticipantsBG001248 ParticipantsBG002

Baseline Hemoglobin A1C (A1C)

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%).

Participants with baseline data for A1C.

Mean

Standard Deviation

Percent

Title	Denominators	Categories
	ParticipantsBG000244 ParticipantsBG001247 ParticipantsBG002

Baseline Body Weight

Mean

Standard Deviation

Kilograms

Title	Denominators	Categories
	ParticipantsBG000250 ParticipantsBG001248 ParticipantsBG002

Baseline Fasting Plasma Glucose

Blood glucose was measured on a fasting basis after at least a 10-hour fast.

Participants with baseline data for Fasting Plasma Glucose.

Mean

Standard Deviation

mg/dL

Title	Denominators	Categories
	ParticipantsBG000250 ParticipantsBG001247 ParticipantsBG002

Static Beta-Cell Sensitivity to Glucose Index

Participants with baseline data for SBCSGI.

Mean

Standard Deviation

SBCSGI (10^-9min^-1)

Title	Denominators	Categories
	ParticipantsBG00058 ParticipantsBG001

Sitting Systolic Blood Pressure

Mean

Standard Deviation

mm Hg

Title	Denominators	Categories
	ParticipantsBG000250 ParticipantsBG001248 ParticipantsBG002

Baseline estimated glomerular filtration rate, eGFR

eGFR is a parameter used to assess kidney function.

Participants with baseline data for eGFR.

Mean

Standard Deviation

mL/min/1.73m^2

Title	Denominators	Categories
	ParticipantsBG000250 ParticipantsBG001248 ParticipantsBG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in A1C at Week 26: Excluding Rescue Approach

A1C is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). This change from baseline reflects the Week 26 A1C minus the Week 0 A1C. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the A1C change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.

Posted

Least Squares Mean

95% Confidence Interval

Percentage

Baseline and Week 26

ID	Title	Description
OG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks
OG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks
OG002	Sitagliptin 100 mg	Sitagliptin 100 mg, oral, once daily for 52 weeks
OG003	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 5 mg + sitagliptin 100 mg, oral, once daily for 52 weeks
OG004	Ertugliflozin 15 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + sitagliptin 100 mg, oral, once daily for 52 weeks

Units	Counts
Participants	OG000250 OG001248 OG002247 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-1.02(-1.14 to -0.90) OG001-1.08(-1.20 to -0.96) OG002-1.05(-1.17 to -0.93) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG003		Constrained longitudinal data analysis		<0.001	Constrained longitudinal data analysis (cLDA) model with fixed effects for treatment, time, baseline eGFR (continuous) and the interaction of time by treatment. Time was treated as a categorical variable.	Difference in the least squares means	-0.46			2-Sided	95	-0.63	-0.30					Superiority or Other
OG002

Primary

Percentage of Participants Who Experienced an Adverse Event (AE): Including Rescue Approach

An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study. Including rescue approach data analysis included data following the initiation of rescue therapy.

The analysis population consists of all randomized participants who received at least 1 dose of study treatment.

Posted

Number

Percentage of participants

Up to 54 weeks

ID	Title	Description
OG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks
OG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks
OG002	Sitagliptin 100 mg	Sitagliptin 100 mg, oral, once daily for 52 weeks
OG003	Ertugliflozin 5 mg + Sitagliptin 100 mg

Primary

Percentage of Participants Who Discontinued Study Treatment Due to an AE: Including Rescue Approach

The analysis population consists of all randomized participants who received at least 1 dose of study treatment.

Posted

Number

Percentage of participants

Up to 52 weeks

ID	Title	Description
OG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks
OG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks
OG002	Sitagliptin 100 mg	Sitagliptin 100 mg, oral, once daily for 52 weeks
OG003	Ertugliflozin 5 mg + Sitagliptin 100 mg

Secondary

Change From Baseline in Body Weight at Week 26: Excluding Rescue Approach

This change from baseline reflects the Week 26 body weight minus the Week 0 body weight. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the body weight change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.

Posted

Least Squares Mean

95% Confidence Interval

Kilograms

Baseline and Week 26

ID	Title	Description
OG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks
OG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks
OG002	Sitagliptin 100 mg	Sitagliptin 100 mg, oral, once daily for 52 weeks
OG003	Ertugliflozin 5 mg + Sitagliptin 100 mg

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 - Excluding Rescue Approach

Blood glucose was measured on a fasting basis after at least a 10-hour fast. This change from baseline reflects the Week 26 FPG minus the Week 0 FPG. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the FPG change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 26

ID	Title	Description
OG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks
OG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks
OG002	Sitagliptin 100 mg	Sitagliptin 100 mg, oral, once daily for 52 weeks
OG003

Secondary

Percentage of Participants Achieving a Hemoglobin A1C of <7% (<53 mmol/Mol) (Raw Proportions): Excluding Rescue Approach

A1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a post-randomization measurement for the A1C change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.

Posted

Number

Percentage of participants

Week 26

ID	Title	Description
OG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks
OG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks
OG002	Sitagliptin 100 mg	Sitagliptin 100 mg, oral, once daily for 52 weeks
OG003	Ertugliflozin 5 mg + Sitagliptin 100 mg

Secondary

Change From Baseline in Static Beta-Cell Sensitivity to Glucose Index at Week 26; Excluding Rescue Approach

Static beta-cell sensitivity to glucose index (SBCSGI) estimates the ratio of insulin secretion (expressed in pmol/min) related to above-basal glucose concentration (expressed in mmol/L * L) following a meal. Blood samples were collected before and after a standard meal and glucose, insulin, and C-peptide levels were analyzed. The C-peptides minimal model was used to estimate the insulin secretion rate (ISR). Analysis included both non-model-based [including insulinogenic index with C-peptide, glucose area under the curve (AUC)/insulin AUC] and model-based [beta cell function and insulin secretion rate at 9 mM glucose] testing. Analysis was performed with non-linear least squares using the Software Architecture Analysis Method (SAAM) II software. SBCSGI was expressed in units of 10^-9 min^-1. Excluding rescue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the beta-cell responsivity static component change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.

Posted

Least Squares Mean

95% Confidence Interval

SBCSGI (10^-9min^-1)

30 min. before and 0, 15, 30, 60, 90, 120, and 180 minutes following the start of the standard meal at Baseline and Week 26

ID	Title	Description
OG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks

Secondary

Change From Baseline in Sitting Systolic Blood Pressure at Week 26: Excluding Rescue Approach

This change from baseline reflects the Week 26 systolic blood pressure minus the Week 0 systolic blood pressure. Excluding recue approach data analysis excluded all data following the initiation of rescue therapy at any time point, in order to avoid the confounding influence of the rescue therapy.

The analysis population consisted of all randomized participants who received at least one dose of study treatment, had a baseline measurement or a post-randomization measurement for the systolic blood pressure change from baseline at Week 26 analysis endpoint subsequent to at least one dose of study treatment.

Posted

Least Squares Mean

95% Confidence Interval

mm Hg

Baseline and Week 26

ID	Title	Description
OG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks
OG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks
OG002	Sitagliptin 100 mg	Sitagliptin 100 mg, oral, once daily for 52 weeks
OG003	Ertugliflozin 5 mg + Sitagliptin 100 mg

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ertugliflozin 5 mg	Ertugliflozin 5 mg, oral, once daily for 52 weeks	12	250	36	250
EG001	Ertugliflozin 15 mg	Ertugliflozin, oral, once daily for 52 weeks	5	248	43	248
EG002	Sitagliptin 100 mg	Sitagliptin 100 mg, oral, once daily for 52 weeks	8	247	28	247
EG003	Ertugliflozin 5 mg + Sitagliptin 100 mg	Ertugliflozin 5 mg + sitagliptin 100 mg, oral, once daily for 52 weeks	9	243	31	243
EG004	Ertugliflozin 15 mg + Sitagliptin 100 mg	Ertugliflozin 15 mg + sitagliptin 100 mg, oral, once daily for 52 weeks	12	244	38	244

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Blood potassium decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG0031 events1 affected243 at risk EG0040 events0 affected244 at risk
Blood sodium decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0021 events1 affected247 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0021 events1 affected247 at risk EG003
Cardiac failure chronic	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Microvascular coronary artery disease	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0021 events1 affected247 at risk EG003
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected248 at risk EG0020 events0 affected247 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected248 at risk EG0021 events1 affected247 at risk EG003
Sciatica	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected248 at risk EG0020 events0 affected247 at risk EG003
Syncope	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Bronchial hyperreactivity	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected248 at risk EG0020 events0 affected247 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected248 at risk EG0020 events0 affected247 at risk EG003
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Femoral hernia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0021 events1 affected247 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0021 events1 affected247 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Obesity	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Cellulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Cellulitis orbital	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Diverticulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0021 events1 affected247 at risk EG003
Gangrene	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0011 events1 affected248 at risk EG0020 events0 affected247 at risk EG003
Gastroenteritis norovirus	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0021 events1 affected247 at risk EG003
Pneumococcal sepsis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Pneumonia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0021 events1 affected247 at risk EG003
Pulmonary tuberculosis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Pyelonephritis acute	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Joint injury	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Overdose	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Nodal marginal zone B-cell lymphoma stage III	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Pancreatic carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Pancreatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Hypertension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0022 events1 affected247 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected250 at risk EG0010 events0 affected248 at risk EG0020 events0 affected247 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG00025 events12 affected250 at risk EG00129 events13 affected248 at risk EG00222 events11 affected247 at risk EG00317 events9 affected243 at risk EG00442 events20 affected244 at risk
Nasopharyngitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0006 events6 affected250 at risk EG00114 events13 affected248 at risk EG0027 events6 affected247 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00024 events20 affected250 at risk EG00123 events19 affected248 at risk EG00213 events13 affected247 at risk EG003

ID	Term
D003924	Diabetes Mellitus, Type 2

ID	Term
C570288	ertugliflozin
D000068900	Sitagliptin Phosphate
D008687	Metformin
D000069036	Insulin Glargine
C057619	glimepiride

Ancestor Terms

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

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OG004-1.52(-1.64 to -1.40)

Ertugliflozin 5 mg + sitagliptin 100 mg, oral, once daily for 52 weeks