A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes (GRADE)

This study is currently recruiting participants.
Verified February 2014 by GRADE Study Group
Sponsor:
Collaborators:
Becton, Dickinson and Company
Bristol-Myers Squibb
Merck Sharp & Dohme Corp.
Novo Nordisk A/S
Hoffmann-La Roche
Sanofi
Information provided by (Responsible Party):
GRADE Study Group
ClinicalTrials.gov Identifier:
NCT01794143
First received: February 13, 2013
Last updated: March 13, 2014
Last verified: February 2014

February 13, 2013
March 13, 2014
May 2013
August 2020   (final data collection date for primary outcome measure)
Time to HbA1c>=7%, while receiving metformin and the randomly assigned study medication [ Time Frame: Quarterly for 4 to 7 years ] [ Designated as safety issue: No ]
The primary metabolic outcome is the time to primary failure defined as an HbA1c>=7% (53mmol/mol), subsequently confirmed.
Same as current
Complete list of historical versions of study NCT01794143 on ClinicalTrials.gov Archive Site
Time to HbA1c>7.5%, while receiving metformin and the randomly assigned study medication. [ Time Frame: Quarterly for 4 to 7 years ] [ Designated as safety issue: No ]
The secondary metabolic outcome is time to HbA1c>7.5% (58 mmol/mol), confirmed.
Same as current
Time to HbA1c>7.5%, while receiving study medications and basal insulin [ Time Frame: Quarterly for 4 to 7 years ] [ Designated as safety issue: No ]
The tertially metabolic outcome is the time to a HbA1c>7.5% (58 mmol/mol), confirmed, while receiving metformin, the originally assigned medication and basal insulin.
Same as current
 
A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes
Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study

The GRADE Study is a pragmatic, unmasked clinical trial that will compare commonly used diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and patient-centered outcomes.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Type 2 Diabetes
  • Comparative Effectiveness of Glycemia-lowering Medications
  • Drug: Sulfonylurea (glimepiride)
    Used in accordance with labeling and/or usual practice.
    Other Name: Glimepiride
  • Drug: DPP-4 inhibitor (sitagliptin)
    Used in accordance with labeling and/or usual practice
    Other Name: Sitagliptin
  • Drug: GLP-1 receptor agonist (liraglutide)
    Used in accordance with labeling and/or usual practice.
    Other Name: Liraglutide
  • Drug: Insulin (glargine)
    Used in accordance with labeling and/or usual practice.
    Other Name: Lantus
  • Active Comparator: Sulfonylurea (glimepiride)
    Sulfonylurea
    Intervention: Drug: Sulfonylurea (glimepiride)
  • Active Comparator: DPP-4 inhibitor
    DPP-4 inhibitor (sitagliptin)
    Intervention: Drug: DPP-4 inhibitor (sitagliptin)
  • Active Comparator: GLP-1 receptor agonist
    GLP-1 receptor agonist (liraglutide)
    Intervention: Drug: GLP-1 receptor agonist (liraglutide)
  • Active Comparator: Insulin (glargine)
    Insulin (glargine), Lantus
    Intervention: Drug: Insulin (glargine)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
5000
Not Provided
August 2020   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Men or women diagnosed with diabetes at age ≥ 30 years (≥ 20 for American Indians)
  2. Duration of diagnosed diabetes < 10 years
  3. HbA1c criteria (at final run-in visit, ~2 weeks prior to randomization): 6.8-8.5%
  4. Taking a daily dose of ≥ 1000 mg metformin for a minimum of 8 weeks at final run-in
  5. Willingness to administer daily subcutaneous injections, take a second diabetes drug after randomization, potentially initiate insulin and intensify insulin therapy if study metabolic goals are not met, perform self-monitoring of blood glucose
  6. Fluent in either English or Spanish
  7. A negative pregnancy test for all females of childbearing potential (i.e. pre-menopausal, and not surgically sterile)
  8. Provision of signed and dated informed consent prior to any study procedures

Exclusion Criteria:

  1. Suspected type 1 diabetes (lean with polyuria, polydipsia, and weight loss with little response to metformin) or "secondary" diabetes due to specific causes (e.g. previously diagnosed monogenic syndromes, pancreatic surgery, pancreatitis)
  2. Current or previous (within past 6 months) treatment with any diabetes drug/glucose-lowering medication other than metformin
  3. More than 10 years of treatment with metformin at time of randomization screening
  4. History of intolerance or allergy or other contraindications to any of the proposed study medications
  5. Resides in the same household with another GRADE study participant
  6. Current need for any specific glucose-lowering medications solely for other conditions, for example for polycystic ovary syndrome
  7. Symptomatic hyperglycemia requiring immediate therapy during screening or run-in, in the judgment of the physician
  8. A life-threatening event within 30 days prior to screening or currently planned major surgery
  9. Any major cardiovascular event in previous year, including history of myocardial infarction, stroke, or vascular procedure such as coronary artery or peripheral bypass grafting, stent placements (peripheral or coronary) or angioplasty.
  10. Plans for pregnancy during the course of the study for women of child-bearing potential
  11. History of or planning bariatric surgery, including banding procedures or surgical gastric and/or intestinal bypass (if banding removed, may be considered eligible after 1 year)
  12. History of congestive heart failure (NYHA 3 or greater)
  13. History of pancreatitis
  14. History of cancer, other than non-melanoma skin cancer, that required therapy in the 5 years prior to randomization
  15. Personal or family history of MEN-2 or family history of medullary thyroid cancer
  16. Serum creatinine >1.4 mg/dl in women and >1.5 mg/dl in men or end stage renal disease requiring renal replacement therapy
  17. History of severe liver disease or acute hepatitis or ALT > 3 times upper limit of normal
  18. Current alcoholism or excessive alcohol intake
  19. Previous organ transplant
  20. Treatment with oral or systemic glucocorticoids (other than short-term treatment, for example for poison ivy) or disease likely to require periodic or regular glucocorticoid therapy (inhaled steroids are allowed)
  21. Treatment with atypical antipsychotics
  22. History of hemolytic anemia, chronic transfusion requirement, or other condition rendering HbA1c results unreliable as indicator of chronic glucose levels, or hematocrit <35 for males and <33 for females
  23. Clinically or medically unstable with expected survival <1 year
  24. Unwillingness to permit sites to contact the PCP to communicate information about the study and the participant's data
  25. No non-study PCP or inability to identify such a PCP (who will provide non-study care) by the time of final run-in
  26. Participation in another interventional clinical trial
  27. Previous randomization in the GRADE study
  28. In the opinion of the principal investigator (PI), any other factor, including language barrier, likely to limit compliance with the protocol
Both
30 Years and older
No
Contact: Heidi Krause-Steinrauf, MS heidi@bsc.gwu.edu
Contact: Paula McGee, MS Paulaf@bsc.gwu.edu
United States
 
NCT01794143
GRADE, 1U01DK098246-01
Yes
GRADE Study Group
GRADE Study Group
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • National Heart, Lung, and Blood Institute (NHLBI)
  • Becton, Dickinson and Company
  • Bristol-Myers Squibb
  • Merck Sharp & Dohme Corp.
  • Novo Nordisk A/S
  • Hoffmann-La Roche
  • Sanofi
Study Chair: David M Nathan, MD Massachusetts General Hospital
GRADE Study Group
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP