A Comparison of Two Treatment Strategies in Older Partici... | NCT02072096

ID	Type	Description	Link
F3Z-MC-IOQL	Other Identifier	Eli Lilly and Company
2013-001473-24	EudraCT Number

Label	Type	Description	Intervention Names
Strategy A (Glucose-Dependent)	Experimental	Participants may receive oral and injectable (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) therapies that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.	Drug: Metformin Drug: Pioglitazone Drug: Acarbose Drug: Linagliptin Drug: Sitagliptin Drug: Liraglutide Drug: Exenatide once weekly (QW) Drug: Exenatide twice daily (BID)
Strategy B (Reference)	Active Comparator	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Insulin glargine is titrated according treatment algorithm. Treatment may last up to 72 weeks.	Drug: Glimepiride Drug: Metformin Drug: Pioglitazone Drug: Acarbose Drug: Linagliptin Drug: Sitagliptin Drug: Insulin Glargine

Name	Type	Description	Arm Group Labels	Other Names
Glimepiride	Drug	Administered orally	Strategy B (Reference)
Metformin

Measure	Description	Time Frame
Percentage of Participants Achieving and Maintaining Individualized Glycated Hemoglobin A1c (HbA1c) Targets Without Clinically Significant Hypoglycemia	Failed to reach and maintain HbA1c target, without clinically significant hypoglycemia, is defined as having 2 consecutive HbA1c > upper limit of HbA1c target over 12 weeks starting from Week 24 for participants with HbA1c data beyond Week 24, or Week 24 HbA1c > upper limit of HbA1c target for participants without HbA1c data beyond Week 24. Clinically significant hypoglycemia is defined as any severe hypoglycemia or repeated hypoglycemia interrupting participants activities or sleep and associated with blood glucose ≤3.9 millimole per liter (mmol/L), or repeated asymptomatic hypoglycemia associated with blood glucose <3.0 mmol/L. Success is defined as lacking of failure.	Baseline to last participant visit (up to 72 weeks)

Measure	Description	Time Frame
Percentage of Participants Requiring Alternative Treatment Due to Glycemic Failure of First Line Injectable Therapy		Baseline to last participant visit (up to 72 weeks)
Number of Participants With Total Hypoglycemia and Other Categories of Hypoglycemia

Measure	Description	Time Frame
Change From Baseline in Adult Low Blood Sugar Survey (ALBSS) Score		Baseline, Week 72
Change From Baseline in European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Score		Baseline, Week 72

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have T2DM based on a history and clinical impression that is consistent with the World Health Organization (WHO) Classification of Diabetes
Have a Clinical Frailty Scale (CFS) score of 4 or above or Total Illness Burden Index (TIBI) score of 5 or above as assessed at screening
Have an A1c >7.3% and <10.9% at study entry and are not achieving desired glycemic control as evidenced by A1c measurement at least 0.4% higher than individualized treatment target set at screening.
Have been treated for at least 3 months prior to the study entry with any of the following treatment options:
- Diet/exercise only (only if they have known contraindications to metformin treatment)
- Any dose of sulfonylurea
- Effective or maximally-tolerated doses of metformin, dipeptidyl-peptidase-4 (DPP-4) inhibitor, thiazolidinedione, or acarbose used in monotherapy or in dual combination. The following doses are considered to be effective:
  - at least 1500 mg of metformin per day
  - At least 30 mg of pioglitazone per day
  - At least 4 mg of rosiglitazone per day
  - At least 75 mg of acarbose per day
  - Any marketed dose of DPP-4 inhibitor

Exclusion Criteria:

Are currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Have participated, within the last 60 days in a clinical trial involving an investigational product other than the investigational product used in this study. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer) should have passed
Have previously completed or withdrawn from this study. This exclusion criterion does not apply to participants who are rescreened prior to randomization
At study entry, have contraindications to sulfonylurea, insulin, or GLP-1 RA
Have a history of pancreatitis, a personal or family history of medullary thyroid carcinoma, or have Multiple Endocrine Neoplasia syndrome type 2
Have taken any injectable glucose-lowering agent, miglitol, meglitinide, Sodium/Glucose cotransporter-2 inhibitor, or other antihyperglycemia treatment that is not listed in the fourth inclusion criterion for more than 10 days within 3 months prior to the study entry
In the opinion of investigator should have an individualized A1c target set at 8% or higher
Have a body mass index (BMI) greater than 45 kg/m^2
Have had more than 1 episode of severe hypoglycemia within 24 weeks prior to the study
Have cardiac disease with functional status that is Class III or IV according to the New York Heart Association Cardiac Disease Classification
Have an estimated glomerular filtration rate (eGFR) <30 milliliter/minute/1.73 m^2 (mL/min/1.73 m^2) or advanced renal disease including history of renal transplantation or currently receiving renal dialysis
Have obvious clinical signs or symptoms or laboratory evidence of liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2.5 times the upper limit of the reference range)
Receive current therapy for a malignancy, other than basal-cell or squamous-cell skin cancer
Received systemic glucocorticoids within the 3 months prior to entry for more than 14 consecutive days
Have any other condition that precludes the participant from following and completing the study

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Suncoast Research Group, LLC		Miami	Florida	33135	United States
New Horizon Research Center

PubMed Identifier	Type	Citation	Retractions
28671753	Derived	Heller SR, Pratley RE, Sinclair A, Festa A, Kiljanski J, Brusko CS, Duan R, Heine RJ. Glycaemic outcomes of an Individualized treatMent aPproach for oldER vulnerable patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus (IMPERIUM). Diabetes Obes Metab. 2018 Jan;20(1):148-156. doi: 10.1111/dom.13051. Epub 2017 Aug 8.

ID	Title	Description
FG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.

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

Percentage of Participants Achieving and Maintaining Individualized Glycated Hemoglobin A1c (HbA1c) Targets Without Clinically Significant Hypoglycemia

Failed to reach and maintain HbA1c target, without clinically significant hypoglycemia, is defined as having 2 consecutive HbA1c > upper limit of HbA1c target over 12 weeks starting from Week 24 for participants with HbA1c data beyond Week 24, or Week 24 HbA1c > upper limit of HbA1c target for participants without HbA1c data beyond Week 24. Clinically significant hypoglycemia is defined as any severe hypoglycemia or repeated hypoglycemia interrupting participants activities or sleep and associated with blood glucose ≤3.9 millimole per liter (mmol/L), or repeated asymptomatic hypoglycemia associated with blood glucose <3.0 mmol/L. Success is defined as lacking of failure.

All participants who received at least one dose of study drug.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline to last participant visit (up to 72 weeks)

ID	Title	Description
OG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.
OG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.

Units	Counts
Participants	OG00098 OG00193

Title

Denominators

Categories

Title	Measurements
	OG00064.5(54.4 to 73.4) OG00154.9(44.6 to 64.9)

Secondary

Percentage of Participants Requiring Alternative Treatment Due to Glycemic Failure of First Line Injectable Therapy

All participants who received at least one dose of study drug.

Posted

Number

percentage of participants

Baseline to last participant visit (up to 72 weeks)

ID	Title	Description
OG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.
OG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.

Units	Counts

Secondary

Number of Participants With Total Hypoglycemia and Other Categories of Hypoglycemia

All participants who received at least one dose of study drug.

Posted

Number

Participants

Baseline to last participant visit (up to 72 weeks)

ID	Title	Description
OG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.
OG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.

Units	Counts

Secondary

Change From Baseline of Urinary Albumin to Creatinine Ratio

The Urinary Albumin to Creatinine Ratio is used in addition to Estimated Glomerular Filtration Rate (eGFR) to measure the incidence and progression of diabetic kidney disease.

All participants who received at least one dose of study drug and had evaluable baseline and post-baseline urinary albumin to creatinine ratio.

Posted

Mean

Standard Deviation

milligram per millimole (mg/mmol)

Baseline, Week 72

ID	Title	Description
OG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.
OG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.

Secondary

Change From Baseline in Body Mass Index (BMI)

All participants who received at least one dose of study drug and had evaluable baseline and post-baseline BMI data.

Posted

Mean

Standard Deviation

kilogram per square meter (kg/m^2)

Baseline, Week 72

ID	Title	Description
OG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label.Treatment may last up to 72 weeks.
OG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.

Units	Counts

Secondary

Change From Baseline of Estimated Glomerular Filtration Rate (eGFR)

The eGFR is used in addition to the Urinary Albumin to Creatinine Ratio to measure the incidence and progression of diabetic kidney disease.

All participants who received at least one dose of study drug and had evaluable baseline and post-baseline eGFR data.

Posted

Mean

Standard Deviation

milliliter per minute/1.73 square meter

Baseline, Week 72

ID	Title	Description
OG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label.Treatment may last up to 72 weeks.
OG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.

Other Pre-specified

Change From Baseline in Adult Low Blood Sugar Survey (ALBSS) Score

Unable to conduct change from baseline analysis due to study closure and lack of endpoint data.

Posted

Baseline, Week 72

ID	Title	Description
OG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.
OG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.

Units	Counts
Participants

Other Pre-specified

Change From Baseline in European Quality of Life-5 Dimensions 5 Levels (EQ-5D-5L) Score

Unable to conduct change from baseline analysis due to study closure and lack of endpoint data.

Posted

Baseline, Week 72

ID	Title	Description
OG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label.Treatment may last up to 72 weeks.
OG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.

Units	Counts
Participants

Other Pre-specified

Change From Baseline in Mini-mental State Examination (MMSE) Score

Unable to conduct change from baseline analysis due to study closure and lack of endpoint data.

Posted

Baseline, Week 72

ID	Title	Description
OG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.
OG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0012 events2 affected93 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Microvascular coronary artery disease	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Myocardial infarction	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0012 events2 affected93 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Retinal vascular thrombosis	Eye disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Gastritis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Chest pain	General disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Cholecystitis chronic	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Appendicitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Cellulitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Pneumonia	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Respiratory tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Muscle rupture	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Hepatic enzyme increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Benign neoplasm of spinal cord	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Benign ovarian tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Prostatic adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0002 events1 affected98 at risk EG0010 events0 affected93 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0002 events2 affected98 at risk EG0010 events0 affected93 at risk
Syncope	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0012 events2 affected93 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Nephrogenic anaemia	Blood and lymphatic system disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Aortic valve stenosis	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Cardiac failure	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Left ventricular hypertrophy	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Mitral valve incompetence	Cardiac disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Palpitations	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0010 events0 affected93 at risk
Tachycardia	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Type v hyperlipidaemia	Congenital, familial and genetic disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Cerumen impaction	Ear and labyrinth disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Sudden hearing loss	Ear and labyrinth disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Goitre	Endocrine disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0013 events3 affected93 at risk
Hyperparathyroidism secondary	Endocrine disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Hypothyroidism	Endocrine disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0012 events2 affected93 at risk
Primary hypothyroidism	Endocrine disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Diplopia	Eye disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Lacrimation increased	Eye disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Vision blurred	Eye disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0004 events4 affected98 at risk EG0010 events0 affected93 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0002 events2 affected98 at risk EG0012 events2 affected93 at risk
Abdominal pain lower	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected98 at risk EG0012 events2 affected93 at risk
Anal pruritus	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Barrett's oesophagus	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Constipation	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0010 events0 affected93 at risk
Dental caries	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG00018 events12 affected98 at risk EG0016 events6 affected93 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Flatulence	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0004 events3 affected98 at risk EG0011 events1 affected93 at risk
Food poisoning	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Gastritis	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0012 events2 affected93 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Hiatus hernia	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Loose tooth	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Systematic Assessment	EG0008 events7 affected98 at risk EG0013 events3 affected93 at risk
Toothache	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0003 events3 affected98 at risk EG0012 events1 affected93 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0005 events3 affected98 at risk EG0010 events0 affected93 at risk
Asthenia	General disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Chest pain	General disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected98 at risk EG0011 events1 affected93 at risk
Fatigue	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Influenza like illness	General disorders	MedDRA 17.1	Systematic Assessment	EG0003 events2 affected98 at risk EG0012 events2 affected93 at risk
Injection site nodule	General disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Malaise	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Oedema	General disorders	MedDRA 18.0	Systematic Assessment	EG0007 events6 affected98 at risk EG0010 events0 affected93 at risk
Oedema peripheral	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0016 events6 affected93 at risk
Peripheral swelling	General disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0012 events2 affected93 at risk
Pyrexia	General disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Hypersensitivity	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Seasonal allergy	Immune system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0012 events1 affected93 at risk
Abscess	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Acarodermatitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Bronchitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0006 events4 affected98 at risk EG0012 events2 affected93 at risk
Cellulitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Chikungunya virus infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0004 events4 affected98 at risk EG0015 events5 affected93 at risk
Colon gangrene	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Conjunctivitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Cystitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Dermatitis infected	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Ear infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Erysipelas	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Fungal infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Fungal skin infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Gastroenteritis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0012 events2 affected93 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0010 events0 affected93 at risk
Gingivitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0003 events2 affected98 at risk EG0010 events0 affected93 at risk
Helicobacter infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Herpes zoster	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Influenza	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0004 events4 affected98 at risk EG0013 events3 affected93 at risk
Laryngitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Lung infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Nasopharyngitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG00017 events10 affected98 at risk EG00118 events16 affected93 at risk
Onychomycosis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0012 events2 affected93 at risk
Rhinitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Sinusitis	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0003 events3 affected98 at risk EG0012 events2 affected93 at risk
Staphylococcal abscess	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Tonsillitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Tooth infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0003 events3 affected98 at risk EG0017 events7 affected93 at risk
Urinary tract infection	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0003 events3 affected98 at risk EG0019 events8 affected93 at risk
Viral infection	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0012 events2 affected93 at risk
Vulvitis	Infections and infestations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Arthropod sting	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0002 events1 affected98 at risk EG0010 events0 affected93 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected98 at risk EG0015 events4 affected93 at risk
Eye contusion	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected98 at risk EG0012 events2 affected93 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0012 events2 affected93 at risk
Laceration	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0002 events1 affected98 at risk EG0015 events4 affected93 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Meniscus injury	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0010 events0 affected93 at risk
Post procedural haematoma	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Scratch	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Arteriogram coronary	Investigations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0012 events1 affected93 at risk
Arthroscopy	Investigations	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0010 events0 affected93 at risk
Aspiration pleural cavity	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Blood creatinine increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Blood glucose abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Blood glucose increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0011 events1 affected93 at risk
Blood pressure diastolic decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Blood pressure diastolic increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Blood pressure systolic decreased	Investigations	MedDRA 16.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Blood pressure systolic increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Blood urea increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Blood uric acid	Investigations	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Cardiac imaging procedure	Investigations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Catheterisation cardiac	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Glomerular filtration rate decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Heart rate increased	Investigations	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Prostatic specific antigen increased	Investigations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Urine analysis abnormal	Investigations	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Weight decreased	Investigations	MedDRA 18.0	Systematic Assessment	EG0005 events5 affected98 at risk EG0010 events0 affected93 at risk
Weight increased	Investigations	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0003 events2 affected98 at risk EG0010 events0 affected93 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0010 events0 affected93 at risk
Fructose intolerance	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Gout	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0013 events3 affected93 at risk
Hypercholesterolaemia	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0004 events4 affected98 at risk EG0010 events0 affected93 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected98 at risk EG0011 events1 affected93 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0018 events1 affected93 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Obesity	Metabolism and nutrition disorders	MedDRA 18.0	Systematic Assessment	EG0002 events1 affected98 at risk EG0010 events0 affected93 at risk
Vitamin d deficiency	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0009 events9 affected98 at risk EG0013 events3 affected93 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0004 events4 affected98 at risk EG0014 events4 affected93 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0009 events9 affected98 at risk EG00111 events11 affected93 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Fibromyalgia	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0003 events2 affected98 at risk EG0010 events0 affected93 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0011 events1 affected93 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0012 events2 affected93 at risk
Osteopenia	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0011 events1 affected93 at risk
Sjogren's syndrome	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Torticollis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Acrochordon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Benign neoplasm of adrenal gland	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Colon adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Thyroid neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Amnesia	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Autonomic neuropathy	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0004 events4 affected98 at risk EG0011 events1 affected93 at risk
Headache	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG00014 events7 affected98 at risk EG0011 events1 affected93 at risk
Paraesthesia	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Parkinson's disease	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Polyneuropathy	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Restless legs syndrome	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Sciatica	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Tremor	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Vascular encephalopathy	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Anxiety	Psychiatric disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Confusional state	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Depression	Psychiatric disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Food aversion	Psychiatric disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Sleep disorder	Psychiatric disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0010 events0 affected93 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Hypertonic bladder	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Microalbuminuria	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0012 events2 affected93 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0002 events1 affected98 at risk EG0010 events0 affected93 at risk
Nocturia	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0013 events3 affected93 at risk
Breast mass	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Prostatomegaly	Reproductive system and breast disorders	MedDRA 18.0	Systematic Assessment	EG0002 events2 affected98 at risk EG0010 events0 affected93 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0012 events1 affected93 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0004 events4 affected98 at risk EG0015 events3 affected93 at risk
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0003 events3 affected98 at risk EG0010 events0 affected93 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Respiratory tract congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0012 events2 affected93 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Nail bed inflammation	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Urticaria contact	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Cataract operation	Surgical and medical procedures	MedDRA 18.0	Systematic Assessment	EG0003 events3 affected98 at risk EG0014 events2 affected93 at risk
Coronary angioplasty	Surgical and medical procedures	MedDRA 18.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Inguinal hernia repair	Surgical and medical procedures	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Large intestinal polypectomy	Surgical and medical procedures	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Lens extraction	Surgical and medical procedures	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Ptosis repair	Surgical and medical procedures	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Tendon sheath lesion excision	Surgical and medical procedures	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Tooth extraction	Surgical and medical procedures	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected98 at risk EG0011 events1 affected93 at risk
Arteriosclerosis	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0011 events1 affected93 at risk
Essential hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0013 events1 affected93 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0005 events5 affected98 at risk EG0015 events4 affected93 at risk
Hypotension	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Peripheral vascular disorder	Vascular disorders	MedDRA 18.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk
Peripheral venous disease	Vascular disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected98 at risk EG0012 events2 affected93 at risk
Subclavian artery stenosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected98 at risk EG0010 events0 affected93 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
C057619	glimepiride
D008687	Metformin
D000077205	Pioglitazone
D020909	Acarbose
D000069476	Linagliptin
D000068900	Sitagliptin Phosphate
D000069450	Liraglutide
D000069036	Insulin Glargine
C494814	BID protein, human

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals
D045162	Thiazolidinediones
D013844	Thiazoles
D013457	Sulfur Compounds
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D014312	Trisaccharides
D009844	Oligosaccharides
D011134	Polysaccharides
D002241	Carbohydrates
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D011799	Quinazolines
D014230	Triazoles
D011719	Pyrazines
D052216	Glucagon-Like Peptide 1
D004763	Glucagon-Like Peptides
D052336	Proglucagon
D005768	Gastrointestinal Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

ID	Title	Description
BG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.
BG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Insulin glargine dose is titrated according to treatment algorithm. Treatment may last up to 72 weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Strategy A (Glucose-Dependent)	Participants may receive oral and injectable therapies (glucagon-like peptide-1 receptor agonists [GLP-1 RA]) that exert a glucose-dependent mode of action. Medications allowed in this arm include: metformin, pioglitazone, acarbose, linagliptin, sitagliptin, liraglutide, exenatide once weekly (QW), and exenatide twice daily (BID). Choice of therapy is based on investigator's discretion. Treatment used in label. Treatment may last up to 72 weeks.			15	98	82	98
EG001	Strategy B (Reference)	Participants will receive glimepiride and may receive basal insulin glargine as a first line injectable therapy. Medications allowed in this arm include: glimepiride, metformin, pioglitazone, acarbose, linagliptin, sitagliptin and basal insulin glargine. Choice of therapy is based on investigator's discretion. Treatment used in label. Dose titrated by treatment algorithm. Treatment may last up to 72 weeks.			14	93	74	93