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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00069784




Registration number
NCT00069784
Ethics application status
Date submitted
1/10/2003
Date registered
6/10/2003
Date last updated
31/01/2013

Titles & IDs
Public title
The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention)
Scientific title
A Multicenter, International Randomized, 2x2 Factorial Design Study to Evaluate the Effects of Lantus (Insulin Glargine) Versus Standard Care, and of Omega-3 Fatty Acids Versus Placebo, in Reducing Cardiovascular Morbidity and Mortality in High Risk People With Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) or Early Type 2 Diabetes Mellitus: The ORIGIN Trial (Outcome Reduction With Initial Glargine Intervention)
Secondary ID [1] 0 0
HOE901/4032
Secondary ID [2] 0 0
LTS6035
Universal Trial Number (UTN)
Trial acronym
ORIGIN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Non-Insulin-Dependent 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - insulin glargine (HOE901)
Treatment: Drugs - omega-3 polyunsaturated fatty acids (PUFA)
Treatment: Drugs - placebo

Experimental: Insulin glargine + omega-3 polyunsaturated fatty acids - * Insulin glargine once daily by subcutaneous injection in a titrated regimen targeting a fasting plasma glucose (FPG) level of =95 mg/dL (5.3 mmol/L)
* One capsule of omega-3 polyunsaturated fatty acids once daily

Experimental: Insulin glargine + placebo - * Insulin glargine once daily by subcutaneous injection in a titrated regimen targeting a fasting plasma glucose (FPG) level of =95 mg/dL (5.3 mmol/L)
* One capsule of placebo once daily

Experimental: Standard care + omega-3 polyunsaturated fatty acids - • One capsule of omega-3 polyunsaturated fatty acids once daily

Placebo comparator: Standard care + placebo - • One capsule of placebo once daily


Treatment: Drugs: insulin glargine (HOE901)
Cartridges for use in a pen device, each containing 3 mL of insulin glargine 100 U/mL solution for injection

Treatment: Drugs: omega-3 polyunsaturated fatty acids (PUFA)
Gelatin capsules (containing icosapent ethyl esters 465 mg and doconexent ethyl esters 375 mg) for oral administration

Treatment: Drugs: placebo
Matching placebo gelatin capsules (containing olive oil) for oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite of the First Occurrence of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI) or Nonfatal Stroke
Timepoint [1] 0 0
from randomization until study cut-off date (median duration of follow-up: 6.2 years)
Primary outcome [2] 0 0
Composite of the First Occurrence of Cardiovascular (CV) Death, Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, Revascularization Procedure or Hospitalization for Heart Failure (HF)
Timepoint [2] 0 0
from randomization until study cut-off date (median duration of follow-up: 6.2 years)
Secondary outcome [1] 0 0
Total Mortality (All Causes)
Timepoint [1] 0 0
from randomization until study cut-off date (median duration of follow-up: 6.2 years)
Secondary outcome [2] 0 0
Composite Diabetic Microvascular Outcome (Kidney or Eye Disease)
Timepoint [2] 0 0
from randomization until study cut-off date (median duration of follow-up: 6.2 years)
Secondary outcome [3] 0 0
Incidence of Development of Type 2 Diabetes Mellitus in Participants With IGT and/or IFG
Timepoint [3] 0 0
from randomization until the last follow-up visit or last OGTT (median duration of follow-up: 6.2 years)

Eligibility
Key inclusion criteria
Inclusion criteria:

I1. Individuals with IFG and/or IGT, or early diabetes, as defined below.

Glucose tolerance status was determined by a 75 g oral glucose tolerance test (OGTT) that was performed fasting (ie, no consumption of food or beverage other than water for at least 8 hours) at the time of screening for all candidates who were not known to have diabetes. The qualifying OGTT could be obtained up to 4 weeks prior to screening provided that anti-diabetic therapy (if any) remained unchanged between the qualifying OGTT and the screening visit. Two plasma glucose values were drawn during the OGTT - a fasting value (FPG) and a value drawn two hours after the 75 g oral glucose load was administered (postprandial plasma glucose [PPG]).

- Impaired glucose tolerance (IGT), defined as a PPG value =140 and <200 mg/dL (ie, =7.8 and <11.1 mmol/L), with a FPG <126 mg/dL (7.0 mmol/L).

OR

- Impaired fasting glucose (IFG), 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]).

OR

- Early type 2 diabetes, defined as a FPG =126 mg/dL (7.0 mmol/L) or a PPG of =200 mg/dL (11.1 mmol/L), or a previous diagnosis of diabetes, and either:

* on no pharmacological treatment (while ambulatory) for at least 10 weeks prior to screening, with screening glycated hemoglobin <150% of the upper limit of normal (ULN) for the laboratory (eg, <9% if the ULN is 6%)
* or taking one oral antidiabetic drug (OAD) from among sulfonylureas (SU), biguanides, thiazolidinediones (TZDs), alpha-glucosidase inhibitors (AGIs), and meglitinides (MGTs) at a stable dose while ambulatory for at least 10 weeks at the time of screening (or for the 10 weeks prior to hospitalization if identified while hospitalized for a CV event), with screening glycated hemoglobin <133% of the ULN for the laboratory (eg, <8% if the ULN is 6%) if taking this medication at half-maximum dose or greater, and glycated hemoglobin <142% of the ULN for the laboratory (eg, <8.5% if the ULN is 6%) if taking this medication at less than half-maximum dose. Individuals taking combination products containing two or more OADs were not eligible.

I2. Men or women aged 50 years and older

I3. At least one of the following CV risk factors:

* previous myocardial infarction (MI) (= 5 days prior to randomization)
* previous stroke (= 5 days prior to randomization)
* previous coronary, carotid or peripheral arterial revascularization
* angina with documented ischemic changes (at least 2 mm ST segment depression on electrocardiogram during a Graded Exercise Test [GXT]; or with a cardiac imaging study positive for ischemia); or unstable angina with documented ischemic changes (either ST segment depression of at least 1 mm or an increase in troponin above the normal range but below the range diagnostic for acute myocardial infarction)
* microalbuminuria or clinical albuminuria (an albumin: creatinine ratio = 30 µg/mg in at least one or timed collection of urine with albumin excretion =20 µg/min or =30 mg/24 hours or total protein excretion =500 mg/24 hours)
* left ventricular hypertrophy by electrocardiogram or echocardiogram
* significant stenosis on angiography of coronary, carotid, or lower extremity arteries (ie, 50% or more stenosis)
* ankle-brachial index < 0.9.

I4. Provision of signed and dated informed consent prior to any study procedures.

I5. Ability and willingness to complete study diaries and questionnaires.

I6. Demonstrated ability to use the self-glucose-monitoring device, and to self-inject insulin prior to randomization.

I7. A negative pregnancy test for all women of childbearing potential (ie, ovulating, pre- menopausal, and not surgically sterile) and the agreement of these women to use a reliable method of birth control to prevent pregnancy during the duration of the study .

I8. Willingness to discontinue prior omega-3 PUFA supplements for the duration of the study.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

E1. Type 1 diabetes.

E2. Requiring ambulatory insulin treatment or uncontrolled or symptomatic hyperglycemia that is likely to require the addition of ambulatory insulin therapy or a new antidiabetic agent either before or within 2 weeks after randomization.

E3. Known anti-glutamic acid decarboxylase antibody (anti-GAD Ab) positivity in the past.

E4. Screening glycated hemoglobin =150% of the ULN for the laboratory (eg, =9% if the ULN is 6%).

E5. Unwillingness to inject insulin or perform self-monitoring of blood glucose.

E6. Nonadherence to the run-in requirement to inject placebo insulin and do capillary glucose monitoring for at least 4 days prior to randomization.

E7. Coronary artery bypass grafting (CABG) either planned at the time of screening, or CABG within the 4 years prior to screening - however, participants with angina, MI, or stroke since a previous CABG will be eligible for randomization, even if the last CABG was within 4 years.

E8. Serum creatinine >2.0 mg/dL (176 µmol/L) at screening.

E9. Active liver disease, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times ULN at screening.

E10. Chronic or recurrent treatment with systemic corticosteroids, or niacin treatment for hyperlipidemia.

E11. Heart failure of New York Heart Association (NYHA) Functional Class III or IV.

E12. Expected survival of <3 years for non-CV causes such as cancer.

E13. Any other factor likely to limit protocol compliance or reporting of adverse events (AEs).

E14. Unwilling or unable to discontinue TZDs.

E15. Simultaneous participation in any other clinical trial of an active pharmacologic agent.

E16. Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data and treatment assignment.

E17. History of hypersensitivity to the investigational products.

E18. Previous randomization in this study.

E19. A prior heart transplant, or awaiting a heart transplant.

E20. Known infection with human immunodeficiency virus (HIV).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2011
Sample size
Target
Accrual to date
Final
12537
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sanofi-Aventis Administrative Office - Cove
Recruitment postcode(s) [1] 0 0
- Cove
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Argentina
State/province [2] 0 0
Buenos Aires
Country [3] 0 0
Austria
State/province [3] 0 0
Vienna
Country [4] 0 0
Belarus
State/province [4] 0 0
Minsk
Country [5] 0 0
Bermuda
State/province [5] 0 0
Hamilton
Country [6] 0 0
Brazil
State/province [6] 0 0
Sao Paulo
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Chile
State/province [8] 0 0
Santiago
Country [9] 0 0
China
State/province [9] 0 0
Beijing
Country [10] 0 0
Colombia
State/province [10] 0 0
Cali
Country [11] 0 0
Croatia
State/province [11] 0 0
Zagreb
Country [12] 0 0
Denmark
State/province [12] 0 0
Horsholm
Country [13] 0 0
Estonia
State/province [13] 0 0
Tatari
Country [14] 0 0
Finland
State/province [14] 0 0
Helsinki
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Germany
State/province [16] 0 0
Berlin
Country [17] 0 0
Hungary
State/province [17] 0 0
Budapest
Country [18] 0 0
India
State/province [18] 0 0
Mumbai
Country [19] 0 0
Ireland
State/province [19] 0 0
Dublin
Country [20] 0 0
Israel
State/province [20] 0 0
Netanya
Country [21] 0 0
Italy
State/province [21] 0 0
Milano
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Seoul
Country [23] 0 0
Latvia
State/province [23] 0 0
Riga
Country [24] 0 0
Lithuania
State/province [24] 0 0
Vilnius
Country [25] 0 0
Mexico
State/province [25] 0 0
Mexico
Country [26] 0 0
Netherlands
State/province [26] 0 0
Gouda
Country [27] 0 0
Norway
State/province [27] 0 0
Lysaker
Country [28] 0 0
Philippines
State/province [28] 0 0
Makati City
Country [29] 0 0
Poland
State/province [29] 0 0
Warszawa
Country [30] 0 0
Romania
State/province [30] 0 0
Bucuresti
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Moscow
Country [32] 0 0
Slovakia
State/province [32] 0 0
Bratislava
Country [33] 0 0
South Africa
State/province [33] 0 0
Midrand
Country [34] 0 0
Spain
State/province [34] 0 0
Barcelona
Country [35] 0 0
Sweden
State/province [35] 0 0
Bromma
Country [36] 0 0
Switzerland
State/province [36] 0 0
Geneva
Country [37] 0 0
Turkey
State/province [37] 0 0
Istanbul
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Surrey
Country [39] 0 0
Venezuela
State/province [39] 0 0
Caracas

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Population Health Research Institute
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The primary objectives of the ORIGIN study were:

* To determine whether insulin glargine-mediated normoglycemia can reduce cardiovascular morbidity and/or mortality in people at high risk for vascular disease with either Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) or early type 2 diabetes;
* To determine whether omega-3 fatty acids can reduce cardiovascular mortality in people with IFG, IGT or early type 2 diabetes.

The secondary objectives of the insulin glargine study were to determine if insulin glargine-mediated normoglycemia can reduce:

* total mortality (all causes);
* the risk of diabetic microvascular outcomes;
* the rate of progression of IGT or IFG to type 2 diabetes.
Trial website
https://clinicaltrials.gov/study/NCT00069784
Trial related presentations / 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. doi: 10.1016/j.ahj.2007.09.009. 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. doi: 10.1111/j.1464-5491.2009.02915.x.
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. doi: 10.2337/dc11-1918. Epub 2012 Feb 8.
ORIGIN Trial Investigators; Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. doi: 10.1056/NEJMoa1203858. Epub 2012 Jun 11.
ORIGIN Trial Investigators; Bosch J, Gerstein HC, Dagenais GR, Diaz R, Dyal L, Jung H, Maggiono AP, Probstfield J, Ramachandran A, Riddle MC, Ryden 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. doi: 10.1056/NEJMoa1203859. Epub 2012 Jun 11.
Cukierman-Yaffe T, Lee SF, Pare G, McQueen M, Hess S, Gerstein HC. Biomarkers of Prevalent and Incident Cognitive Dysfunction in People with Dysglycemia: Data from the ORIGIN Trial. J Alzheimers Dis. 2022;87(3):1143-1150. doi: 10.3233/JAD-215195.
Shao H, Kianmehr H, Guo J, Li P, Fonseca V, Shi L. Efficacy of iGlarLixi on 5-year risk of diabetes-related complications: A simulation study. J Diabetes Complications. 2022 Mar;36(3):108132. doi: 10.1016/j.jdiacomp.2022.108132. Epub 2022 Jan 25.
Pigeyre M, Hess S, Gomez MF, Asplund O, Groop L, Pare G, Gerstein H. Validation of the classification for type 2 diabetes into five subgroups: a report from the ORIGIN trial. Diabetologia. 2022 Jan;65(1):206-215. doi: 10.1007/s00125-021-05567-4. Epub 2021 Oct 21.
Wang A, Gerstein HC, Lee SF, Hess S, Pare G, Ryden L, Mellbin LG. Testosterone and sex hormone-binding globulin in dysglycemic women at high cardiovascular risk: A report from the Outcome Reduction with an Initial Glargine Intervention trial. Diab Vasc Dis Res. 2021 Mar-Apr;18(2):14791641211002475. doi: 10.1177/14791641211002475.
Pigeyre M, Sjaarda J, Chong M, Hess S, Bosch J, Yusuf S, Gerstein H, Pare G. ACE and Type 2 Diabetes Risk: A Mendelian Randomization Study. Diabetes Care. 2020 Apr;43(4):835-842. doi: 10.2337/dc19-1973. Epub 2020 Feb 4.
Theriault S, Sjaarda J, Chong M, Hess S, Gerstein H, Pare G. Identification of Circulating Proteins Associated With Blood Pressure Using Mendelian Randomization. Circ Genom Precis Med. 2020 Feb;13(1):e002605. doi: 10.1161/CIRCGEN.119.002605. Epub 2020 Jan 12.
Gerstein HC, Pare G, McQueen MJ, Lee SF, Bangdiwala SI, Kannt A, Hess S; ORIGIN Trial Investigators. Novel Biomarkers for Change in Renal Function in People With Dysglycemia. Diabetes Care. 2020 Feb;43(2):433-439. doi: 10.2337/dc19-1604. Epub 2019 Nov 14.
Pigeyre M, Sjaarda J, Mao S, Chong M, Hess S, Yusuf S, Gerstein H, Pare G. Identification of Novel Causal Blood Biomarkers Linking Metabolically Favorable Adiposity With Type 2 Diabetes Risk. Diabetes Care. 2019 Sep;42(9):1800-1808. doi: 10.2337/dc18-2444. Epub 2019 Jun 24.
Cukierman-Yaffe T, Bosch J, Jung H, Punthakee Z, Gerstein HC. Hypoglycemia and Incident Cognitive Dysfunction: A Post Hoc Analysis From the ORIGIN Trial. Diabetes Care. 2019 Jan;42(1):142-147. doi: 10.2337/dc18-0690. Epub 2018 Nov 13.
Mohammadi-Shemirani P, Sjaarda J, Gerstein HC, Treleaven DJ, Walsh M, Mann JF, McQueen MJ, Hess S, Pare G. A Mendelian Randomization-Based Approach to Identify Early and Sensitive Diagnostic Biomarkers of Disease. Clin Chem. 2019 Mar;65(3):427-436. doi: 10.1373/clinchem.2018.291104. Epub 2018 Oct 18.
Morieri ML, Gao H, Pigeyre M, Shah HS, Sjaarda J, Mendonca C, Hastings T, Buranasupkajorn P, Motsinger-Reif AA, Rotroff DM, Sigal RJ, Marcovina SM, Kraft P, Buse JB, Wagner MJ, Gerstein HC, Mychaleckyj JC, Pare G, Doria A. Genetic Tools for Coronary Risk Assessment in Type 2 Diabetes: A Cohort Study From the ACCORD Clinical Trial. Diabetes Care. 2018 Nov;41(11):2404-2413. doi: 10.2337/dc18-0709. Epub 2018 Sep 27.
Birkeland KI, Grill V, Wium C, McQueen MJ, Lopez-Jaramillo P, Lee SF, Gerstein HC. The association of basal insulin treatment versus standard care with outcomes in anti-GAD positive and negative subjects: A post-hoc analysis of the ORIGIN trial. Diabetes Obes Metab. 2019 Feb;21(2):429-433. doi: 10.1111/dom.13528. Epub 2018 Oct 3.
Sjaarda J, Gerstein H, Chong M, Yusuf S, Meyre D, Anand SS, Hess S, Pare G. Blood CSF1 and CXCL12 as Causal Mediators of Coronary Artery Disease. J Am Coll Cardiol. 2018 Jul 17;72(3):300-310. doi: 10.1016/j.jacc.2018.04.067. Epub 2018 Jul 9.
Gerstein HC, Ferrannini E, Riddle MC, Yusuf S; ORIGIN Trial Investigators. Insulin resistance and cardiovascular outcomes in the ORIGIN trial. Diabetes Obes Metab. 2018 Mar;20(3):564-570. doi: 10.1111/dom.13112. Epub 2017 Oct 8.
Papademetriou V, Nylen ES, Doumas M, Probstfield J, Mann JFE, Gilbert RE, Gerstein HC. Chronic Kidney Disease, Basal Insulin Glargine, and Health Outcomes in People with Dysglycemia: The ORIGIN Study. Am J Med. 2017 Dec;130(12):1465.e27-1465.e39. doi: 10.1016/j.amjmed.2017.05.047. Epub 2017 Aug 31.
Yates T, Davies MJ, Jung H, Bosch J, Spinas GA, Sreenan S, Commerford P, Gerstein HC; ORGIN investigators. Effect of insulin glargine on recreational physical activity and TV viewing: Analysis of the randomised ORIGIN trial. Diabetes Res Clin Pract. 2017 Oct;132:137-143. doi: 10.1016/j.diabres.2017.07.035. Epub 2017 Jul 31.
Rautio A, Boman K, Gerstein HC, Hernestal-Boman J, Lee SF, Olofsson M, Mellbin LG. The effect of basal insulin glargine on the fibrinolytic system and von Willebrand factor in people with dysglycaemia and high risk for cardiovascular events: Swedish substudy of the Outcome Reduction with an Initial Glargine Intervention trial. Diab Vasc Dis Res. 2017 Jul;14(4):345-352. doi: 10.1177/1479164117703034. Epub 2017 Apr 12.
Gerstein HC, Pare G, McQueen MJ, Lee SF, Hess S; ORIGIN Trial Investigators. Validation of the ORIGIN Cardiovascular Biomarker Panel and the Value of Adding Troponin I in Dysglycemic People. J Clin Endocrinol Metab. 2017 Jul 1;102(7):2251-2257. doi: 10.1210/jc.2017-00273.
Gerstein HC, Pare G, Hess S, Ford RJ, Sjaarda J, Raman K, McQueen M, Lee S, Haenel H, Steinberg GR; ORIGIN Investigators. Growth Differentiation Factor 15 as a Novel Biomarker for Metformin. Diabetes Care. 2017 Feb;40(2):280-283. doi: 10.2337/dc16-1682. Epub 2016 Dec 14.
ORIGIN Trial Investigators. Cardiovascular and Other Outcomes Postintervention With Insulin Glargine and Omega-3 Fatty Acids (ORIGINALE). Diabetes Care. 2016 May;39(5):709-16. doi: 10.2337/dc15-1676. Epub 2015 Dec 17.
Gerstein HC, Pare G, McQueen MJ, Haenel H, Lee SF, Pogue J, Maggioni AP, Yusuf S, Hess S; Outcome Reduction With Initial Glargine Intervention Trial Investigators. Identifying Novel Biomarkers for Cardiovascular Events or Death in People With Dysglycemia. Circulation. 2015 Dec 15;132(24):2297-304. doi: 10.1161/CIRCULATIONAHA.115.015744. Epub 2015 Oct 30.
Cukierman-Yaffe T, Bosch J, Diaz R, Dyal L, Hancu N, Hildebrandt P, Lanas F, Lewis BS, Marre M, Yale JF, Yusuf S, Gerstein HC; ORIGIN Investigators. Effects of basal insulin glargine and omega-3 fatty acid on cognitive decline and probable cognitive impairment in people with dysglycaemia: a substudy of the ORIGIN trial. Lancet Diabetes Endocrinol. 2014 Jul;2(7):562-72. doi: 10.1016/S2213-8587(14)70062-2. Epub 2014 Jun 2.
ORIGIN trial investigators; Gilbert RE, Mann JF, Hanefeld M, Spinas G, Bosch J, Yusuf S, Gerstein HC. Basal insulin glargine and microvascular outcomes in dysglycaemic individuals: results of the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial. Diabetologia. 2014 Jul;57(7):1325-31. doi: 10.1007/s00125-014-3238-4. Epub 2014 Apr 26.
Lopez-Jaramillo P, Cohen DD, Gomez-Arbelaez D, Bosch J, Dyal L, Yusuf S, Gerstein HC; ORIGIN Trial Investigators. Association of handgrip strength to cardiovascular mortality in pre-diabetic and diabetic patients: a subanalysis of the ORIGIN trial. Int J Cardiol. 2014 Jun 15;174(2):458-61. doi: 10.1016/j.ijcard.2014.04.013. Epub 2014 Apr 13. No abstract available.
Lamy A, Tong W, Jung H, Gafni A, Singh K, Tyrwhitt J, Yusuf S, Gerstein HC; ORIGIN Investigators. Cost implications of the use of basal insulin glargine in people with early dysglycemia: the ORIGIN trial. J Diabetes Complications. 2014 Jul-Aug;28(4):553-8. doi: 10.1016/j.jdiacomp.2014.02.012. Epub 2014 Mar 2.
Bordeleau L, Yakubovich N, Dagenais GR, Rosenstock J, Probstfield J, Chang Yu P, Ryden LE, Pirags V, Spinas GA, Birkeland KI, Ratner RE, Marin-Neto JA, Keltai M, Riddle MC, Bosch J, Yusuf S, Gerstein HC; ORIGIN Trial Investigators. The association of basal insulin glargine and/or n-3 fatty acids with incident cancers in patients with dysglycemia. Diabetes Care. 2014;37(5):1360-6. doi: 10.2337/dc13-1468. Epub 2014 Feb 26.
ORIGIN Trial Investigators; Mellbin LG, Ryden L, Riddle MC, Probstfield J, Rosenstock J, Diaz R, Yusuf S, Gerstein HC. Does hypoglycaemia increase the risk of cardiovascular events? A report from the ORIGIN trial. Eur Heart J. 2013 Oct;34(40):3137-44. doi: 10.1093/eurheartj/eht332. Epub 2013 Sep 2.
ORIGIN Trial Investigators. Characteristics associated with maintenance of mean A1C<6.5% in people with dysglycemia in the ORIGIN trial. Diabetes Care. 2013 Oct;36(10):2915-22. doi: 10.2337/dc12-2238. Epub 2013 May 8.
Lonn EM, Bosch J, Diaz R, Lopez-Jaramillo P, Ramachandran A, Hancu N, Hanefeld M, Krum H, Ryden L, Smith S, McQueen MJ, Dyal L, Yusuf S, Gerstein HC; GRACE and ORIGIN Investigators. Effect of insulin glargine and n-3FA on carotid intima-media thickness in people with dysglycemia at high risk for cardiovascular events: the glucose reduction and atherosclerosis continuing evaluation study (ORIGIN-GRACE). Diabetes Care. 2013 Sep;36(9):2466-74. doi: 10.2337/dc12-2129. Epub 2013 Apr 5.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00069784