The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention)

This study has been completed.

Sponsor:

Collaborator:

Population Health Research Institute

Information provided by (Responsible Party):

Sanofi

ClinicalTrials.gov Identifier:

NCT00069784

First received: October 1, 2003

Last updated: January 24, 2013

Last verified: January 2013

History of Changes

Results First Received: December 18, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Factorial Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Diabetes Mellitus, Non-Insulin-Dependent
Interventions:	Drug: insulin glargine (HOE901) Drug: omega-3 polyunsaturated fatty acids (PUFA) Drug: placebo Device: reusable pen device for insulin injection

Participant Flow

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Baseline Characteristics

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Reporting Groups

	Description
Insulin Glargine	Treatment with Insulin Glargine with or without omega-3 polyunsaturated fatty acids
Standard Care	Standard care with or without omega-3 polyunsaturated fatty acids
Total	Total of all reporting groups

Baseline Measures

	Insulin Glargine	Standard Care	Total
Number of Participants [units: participants]	6264	6273	12537
Age [units: years] Mean ± Standard Deviation	63.5 ± 7.8	63.5 ± 7.9	63.5 ± 7.8
Gender, Customized [units: participants]
Male	4181	3969	8150
Female	2082	2304	4386
Missing value	1	0	1
Baseline Weight ^[1] [units: kg] Mean ± Standard Deviation	83.33 ± 16.77	83.13 ± 17.28	83.23 ± 17.03
Baseline Body Mass Index ^[2] [units: kg/m²] Mean ± Standard Deviation	29.77 ± 5.17	29.88 ± 5.33	29.82 ± 5.25
Any previous cardiovascular event [units: participants]
No	2552	2607	5159
Yes	3712	3666	7378
Diabetes diagnosis at time of screening ^[3] [units: participants]
IFG and/or IGT	735	717	1452
Newly diagnosed diabetic	365	395	760
Established diabetes with no OAD treatment	1414	1467	2881
Established diabetes with one OAD treatment	3748	3692	7440
Unclear diabetes status	2	2	4
Duration of diabetes for established diabetes patients ^[4] [units: years] Median ( Inter-Quartile Range )	3.50 ( 1.50 to 7.50 )	3.50 ( 1.50 to 7.50 )	3.50 ( 1.50 to 7.50 )
Glycated Hemoglobin A1c (HbA1c) ^[5] [units: percent] Median ( Inter-Quartile Range )	6.41 ( 5.81 to 7.18 )	6.40 ( 5.81 to 7.16 )	6.40 ( 5.81 to 7.18 )
Fasting Plasma Glucose ^[6] [units: mmol/L] Median ( Inter-Quartile Range )	6.94 ( 6.05 to 8.20 )	6.90 ( 6.00 to 8.20 )	6.94 ( 6.05 to 8.20 )

[1]	Due to missing values, N=6256 for insulin glargine and N=6271 for standard care.
[2]	Due to missing values, N=6251 for insulin glargine and N=6270 for standard care.
[3]	IFG = Impaired Fasting Glucose defined as a Postprandial Plasma Glucose (PPG) value ≥140 and <200 mg/dL (ie, ≥7.8 and <11.1 mmol/L), with a Fasting Plasma Glucose (FPG) <126 mg/dL (7.0 mmol/L) IGT = Impaired Glucose Tolerance defined as an FPG ≥110 and <126 mg/dL (≥6.1 and <7 mmol/L), without diabetes mellitus (PPG must be <200 mg/dL [11.1 mmol/L]) OAD = oral antidiabetic drug
[4]	Population of patients with established diabetes. Due to missing values, N=5148 for insulin glargine and N=5141 for standard care.
[5]	Due to missing values, N=6175 for insulin glargine and N=6189 for standard care.
[6]	Due to missing values, N=6248 for insulin glargine and N=6266 for standard care.

Outcome Measures

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1. Primary:

Composite of the First Occurrence of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI) or Nonfatal Stroke [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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2. Primary:

Composite of the First Occurrence of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, Revascularization Procedure or Hospitalization for Heart Failure (HF) [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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3. Secondary:

Total Mortality (All Causes) [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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4. Secondary:

Composite Diabetic Microvascular Outcome (Kidney or Eye Disease) [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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5. Secondary:

Incidence of Development of Type 2 Diabetes Mellitus in Participants With IGT and/or IFG [ Time Frame: from randomization until the last follow-up visit or last OGTT (median duration of follow-up: 6.2 years) ]

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6. Other Pre-specified:

Number of Patients With Various Types of Symptomatic Hypoglycemia Events [ Time Frame: on-treatment period (median duration of follow-up: 6.2 years) ]

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7. Other Pre-specified:

Number of Patients With First Occurrence of Any Type of Cancer [ Time Frame: from randomization until study cut-off date (median duration of follow-up: 6.2 years) ]

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Serious Adverse Events

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Time Frame	Adverse events (AEs) were assessed through the study. The median duration of follow-up was 6.2 years.
Additional Description	Aside from hypoglycemia and cancer, serious AEs were only captured if the event was considered related to a study drug. Non-serious AEs were only captured if the event resulted in some modification (suspension, alteration or cessation) in the dose of a study drug. This creates a bias for the comparison between insulin glargine and standard care.

Reporting Groups

	Description
Insulin Glargine	Treatment with Insulin Glargine with or without omega-3 polyunsaturated fatty acids
Standard Care	Standard care with or without omega-3 polyunsaturated fatty acids

Serious Adverse Events

	Insulin Glargine	Standard Care
Total, serious adverse events
# participants affected / at risk	303/6231 (4.86%)	232/6273 (3.70%)
Blood and lymphatic system disorders
Anaemia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Coagulopathy ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Hypochromic anaemia ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Idiopathic thrombocytopenic purpura ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Lymphadenopathy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Cardiac disorders
Myocardial infarction ^{* 1}
# participants affected / at risk	10/6231 (0.16%)	9/6273 (0.14%)
Angina unstable ^{* 1}
# participants affected / at risk	9/6231 (0.14%)	11/6273 (0.18%)
Acute myocardial infarction ^{* 1}
# participants affected / at risk	8/6231 (0.13%)	4/6273 (0.06%)
Cardiac failure congestive ^{* 1}
# participants affected / at risk	6/6231 (0.10%)	6/6273 (0.10%)
Arrhythmia supraventricular ^{* 1}
# participants affected / at risk	3/6231 (0.05%)	1/6273 (0.02%)
Atrial fibrillation ^{* 1}
# participants affected / at risk	3/6231 (0.05%)	3/6273 (0.05%)
Angina pectoris ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	3/6273 (0.05%)
Cardiac arrest ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	1/6273 (0.02%)
Cardiac failure ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	3/6273 (0.05%)
Supraventricular tachycardia ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Acute coronary syndrome ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Arrhythmia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Bradycardia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Ventricular extrasystoles ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Ventricular fibrillation ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Ventricular tachycardia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Atrioventricular block ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	3/6273 (0.05%)
Atrioventricular block second degree ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Cardiac disorder ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Coronary artery disease ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Coronary artery occlusion ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Myocardial ischaemia ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Pericardial disease ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Congenital, familial and genetic disorders
Skull malformation ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Ear and labyrinth disorders
Tinnitus ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Vertigo ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Inner ear disorder ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Otosclerosis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Eye disorders
Vitreous haemorrhage ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Retinal haemorrhage ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Retinal oedema ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Visual impairment ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Blindness ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Diabetic retinopathy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Eversion of lacrimal punctum ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Retinal vein thrombosis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Gastrointestinal disorders
Gastrointestinal haemorrhage ^{* 1}
# participants affected / at risk	5/6231 (0.08%)	0/6273 (0.00%)
Abdominal pain ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Pancreatitis ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Rectal haemorrhage ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Abdominal pain upper ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Abdominal strangulated hernia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Colitis ulcerative ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Diarrhoea ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Duodenal varices ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Gastric ulcer ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Gastrointestinal ulcer haemorrhage ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Oesophagitis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Pancreatitis acute ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Peptic ulcer haemorrhage ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Abdominal distension ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Colitis ischaemic ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Constipation ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	2/6273 (0.03%)
Dyspepsia ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Gastritis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Gastrointestinal ulcer ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Lower gastrointestinal haemorrhage ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Pancreatolithiasis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Upper gastrointestinal haemorrhage ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
General disorders
Death ^{* 1}
# participants affected / at risk	11/6231 (0.18%)	14/6273 (0.22%)
Chest pain ^{* 1}
# participants affected / at risk	6/6231 (0.10%)	2/6273 (0.03%)
Non-cardiac chest pain ^{* 1}
# participants affected / at risk	4/6231 (0.06%)	0/6273 (0.00%)
Oedema peripheral ^{* 1}
# participants affected / at risk	3/6231 (0.05%)	0/6273 (0.00%)
Sudden death ^{* 1}
# participants affected / at risk	3/6231 (0.05%)	1/6273 (0.02%)
Cardiac death ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Device failure ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Pyrexia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Sudden cardiac death ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Hernia obstructive ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Hepatobiliary disorders
Cholelithiasis ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	1/6273 (0.02%)
Hepatic cirrhosis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Hepatitis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Cholecystitis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Cholecystitis acute ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	2/6273 (0.03%)
Hepatitis toxic ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Liver disorder ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Immune system disorders
Drug hypersensitivity ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Hypersensitivity ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Infections and infestations
Pneumonia ^{* 1}
# participants affected / at risk	5/6231 (0.08%)	6/6273 (0.10%)
Gastroenteritis ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	3/6273 (0.05%)
Sepsis ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Urinary tract infection ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	1/6273 (0.02%)
Abdominal abscess ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Anal abscess ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Diverticulitis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Herpes zoster ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Infective exacerbation of chronic obstructive airways disease ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Respiratory tract infection ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Bronchitis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	4/6273 (0.06%)
Cellulitis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
H1N1 influenza ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Pseudomonas infection ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Rectal abscess ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Wound infection ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Injury, poisoning and procedural complications
Accidental overdose ^{* 1}
# participants affected / at risk	5/6231 (0.08%)	0/6273 (0.00%)
Fracture ^{* 1}
# participants affected / at risk	3/6231 (0.05%)	3/6273 (0.05%)
Toxicity to various agents ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	1/6273 (0.02%)
Intentional overdose ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Radius fracture ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Splenic rupture ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Subdural haematoma ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Wrist fracture ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Fall ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Gun shot wound ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Hip fracture ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Joint dislocation ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Meniscus lesion ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Overdose ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Tendon injury ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Upper limb fracture ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Investigations
Arteriogram coronary ^{* 1}
# participants affected / at risk	4/6231 (0.06%)	1/6273 (0.02%)
Weight increased ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Arteriogram carotid ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Biopsy lymph gland ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Colonoscopy ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Diagnostic procedure ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Ureteroscopy ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Cystoscopy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Investigation ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Liver function test abnormal ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Metabolism and nutrition disorders
Hypoglycaemia ^{* 1}
# participants affected / at risk	36/6231 (0.58%)	15/6273 (0.24%)
Hypoglycaemic unconsciousness ^{* 1}
# participants affected / at risk	21/6231 (0.34%)	0/6273 (0.00%)
Hypoglycaemic seizure ^{* 1}
# participants affected / at risk	7/6231 (0.11%)	0/6273 (0.00%)
Hyperglycaemia ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Hypertriglyceridaemia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Hypokalaemia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Lactic acidosis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Cachexia ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Diabetic foot ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Shock hypoglycaemic ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Musculoskeletal and connective tissue disorders
Arthritis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Muscle spasms ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Osteoarthritis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Osteoporotic fracture ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Spinal column stenosis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Chondrocalcinosis pyrophosphate ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Lumbar spinal stenosis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Osteoporosis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Rheumatoid arthritis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Spinal disorder ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Spinal osteoarthritis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant ^{* 1}
# participants affected / at risk	4/6231 (0.06%)	3/6273 (0.05%)
Pancreatic carcinoma ^{* 1}
# participants affected / at risk	4/6231 (0.06%)	5/6273 (0.08%)
Prostate cancer ^{* 1}
# participants affected / at risk	4/6231 (0.06%)	5/6273 (0.08%)
Adenocarcinoma ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Adrenal adenoma ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Basal cell carcinoma ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Bladder cancer ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Breast cancer ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Chronic lymphocytic leukaemia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Colon cancer ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	2/6273 (0.03%)
Colon neoplasm ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Colorectal cancer ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Endometrial cancer ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Gastric cancer ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Hepatic neoplasm malignant non-resectable ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Lymphoma ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Malignant melanoma stage I ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Multiple myeloma ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Myelodysplastic syndrome ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Neoplasm malignant ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	2/6273 (0.03%)
Non-small cell lung cancer ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Pancreatic neoplasm ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Pituitary tumour benign ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Rectosigmoid cancer stage III ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Renal cell carcinoma ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Salivary gland neoplasm ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Transitional cell carcinoma ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Acute myeloid leukaemia ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Brain neoplasm ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Gallbladder cancer ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Hepatic neoplasm malignant ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Lymphoproliferative disorder ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Mediastinum neoplasm ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Metastases to lung ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Metastatic neoplasm ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Metastatic squamous cell carcinoma ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Non-Hodgkin's lymphoma ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Pseudomyxoma peritonei ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Rectal cancer ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Renal cancer ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Uterine cancer ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Nervous system disorders
Hypoglycaemic coma ^{* 1}
# participants affected / at risk	18/6231 (0.29%)	2/6273 (0.03%)
Cerebrovascular accident ^{* 1}
# participants affected / at risk	8/6231 (0.13%)	5/6273 (0.08%)
Syncope ^{* 1}
# participants affected / at risk	4/6231 (0.06%)	1/6273 (0.02%)
Cerebral haemorrhage ^{* 1}
# participants affected / at risk	3/6231 (0.05%)	0/6273 (0.00%)
Grand mal convulsion ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Cerebral infarction ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Cranial nerve palsies multiple ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Dementia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	3/6273 (0.05%)
Dizziness ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Ischaemic cerebral infarction ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Neurological symptom ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Subarachnoid haemorrhage ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
VIIth nerve paralysis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Cerebral artery embolism ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Cerebrovascular disorder ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Cognitive disorder ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Convulsion ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Diabetic neuropathy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	2/6273 (0.03%)
Haemorrhagic stroke ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Ischaemic stroke ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	2/6273 (0.03%)
Lumbar radiculopathy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Neuropathy peripheral ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Polyneuropathy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Transient ischaemic attack ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	3/6273 (0.05%)
Psychiatric disorders
Abnormal behaviour ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Hypomania ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Major depression ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Confusional state ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Renal and urinary disorders
Nephrolithiasis ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Renal failure ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	1/6273 (0.02%)
Urinary tract obstruction ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	0/6273 (0.00%)
Haematuria ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Renal failure acute ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	2/6273 (0.03%)
Nephropathy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Renal failure chronic ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Ureteric obstruction ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Urethral stenosis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Urinary retention ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	2/6273 (0.03%)
Reproductive system and breast disorders
Postmenopausal haemorrhage ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Prostatism ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease ^{* 1}
# participants affected / at risk	4/6231 (0.06%)	2/6273 (0.03%)
Acute pulmonary oedema ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Asphyxia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Epistaxis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	4/6273 (0.06%)
Pleural effusion ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Pulmonary oedema ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Respiratory failure ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Acute respiratory failure ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Bronchospasm ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Pulmonary embolism ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Skin and subcutaneous tissue disorders
Diabetic ulcer ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Erythema ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Erythema multiforme ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Ecchymosis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Surgical and medical procedures
Cardiac pacemaker insertion ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	1/6273 (0.02%)
Coronary artery bypass ^{* 1}
# participants affected / at risk	2/6231 (0.03%)	1/6273 (0.02%)
Cholecystostomy ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Hip arthroplasty ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Intestinal resection ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Urethral dilation procedure ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Vitrectomy ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Abdominal hernia repair ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Angioplasty ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Cholecystectomy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Colporrhaphy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Hospitalisation ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Parotidectomy ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Percutaneous coronary intervention ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Vascular disorders
Hypotension ^{* 1}
# participants affected / at risk	3/6231 (0.05%)	0/6273 (0.00%)
Aortic aneurysm ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Embolism ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Femoral artery occlusion ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Hypertension ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	3/6273 (0.05%)
Hypertensive emergency ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Iliac artery stenosis ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Intermittent claudication ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	1/6273 (0.02%)
Ischaemia ^{* 1}
# participants affected / at risk	1/6231 (0.02%)	0/6273 (0.00%)
Accelerated hypertension ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Arterial occlusive disease ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Deep vein thrombosis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Orthostatic hypotension ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Peripheral vascular disorder ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)
Thrombosis ^{* 1}
# participants affected / at risk	0/6231 (0.00%)	1/6273 (0.02%)

*	Events were collected by non-systematic assessment
1	Term from vocabulary, MedDRA 14.0

Other Adverse Events

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: "The Steering Committee will be responsible for preparing summaries of the study results for publication in the medical literature, and will have the right to submit such summaries for publication after a review by the sponsor. In such cases comments from the sponsor to the Steering Committee are to be provided within 15 working days. All comments will be carefully considered by the Steering Committee who nevertheless have the final decision on the content of the manuscript."

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Trial Transparency Team
Organization: sanofi
e-mail: Contact_US@sanofi.com

Publications of Results:

ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Rydén LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. Epub 2012 Jun 11.

ORIGIN Trial Investigators, Bosch J, Gerstein HC, Dagenais GR, Díaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Ramachandran A, Riddle MC, Rydén LE, Yusuf S. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N Engl J Med. 2012 Jul 26;367(4):309-18. Epub 2012 Jun 11.

Other Publications:

Origin Trial Investigators, Gerstein H, Yusuf S, Riddle MC, Ryden L, Bosch J. Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention). Am Heart J. 2008 Jan;155(1):26-32, 32.e1-6. Epub 2007 Nov 26.

Hanefeld M, Koehler C, Hoffmann C, Wilhelm K, Kamke W, Gerstein H. Effect of targeting normal fasting glucose levels with basal insulin glargine on glycaemic variability and risk of hypoglycaemia: a randomized, controlled study in patients with early Type 2 diabetes. Diabet Med. 2010 Feb;27(2):175-80.

Badings EA, Dyal L, Schoterman L, Lok DJ, Stoel I, Gerding MN, Gerstein HC, Tijssen JG. Strategies to detect abnormal glucose metabolism in people at high risk of cardiovascular disease from the ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial population. J Diabetes. 2011 Sep;3(3):232-7. doi: 10.1111/j.1753-0407.2011.00124.x.

Ramachandran A, Riddle MC, Kabali C, Gerstein HC; ORIGIN Investigators. Relationship between A1C and fasting plasma glucose in dysglycemia or type 2 diabetes: an analysis of baseline data from the ORIGIN trial. Diabetes Care. 2012 Apr;35(4):749-53. Epub 2012 Feb 8.

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT00069784 History of Changes
Other Study ID Numbers:	LTS6035, HOE901/4032
Study First Received:	October 1, 2003
Results First Received:	December 18, 2012
Last Updated:	January 24, 2013
Health Authority:	United States: Food and Drug Administration

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