Phase 3
Completed N=5,047
A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes
Type 2 Diabetes · Comparative Effectiveness of Glycemia-lowering Medications
Source: ClinicalTrials.gov NCT01794143 ↗
Enrolled (actual)
5,047
Serious AEs
8.2%
Results posted
Feb 2026
Primary outcomePrimary: Time to HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication — 1.3; 1.3; 1.5; 0.8 years
◆ Published Evidence
Emerging
9citations · ~9 / year
Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes: The GRADE Randomized Clinical Trial.
Summary
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.
Linked Publications (5)
-
Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes: The GRADE Randomized Clinical Trial.
-
Weight Gain Was Associated With Worsening Glycemia and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes Independent of Diabetes Medication in the GRADE Randomized Controlled Trial.
-
Differences in Prevalence and Incidence of Electrocardiogram Abnormalities and Cardiovascular Autonomic Neuropathy Among Randomized Glucose-Lowering Treatments in Early Type 2 Diabetes: The Glycemia Reduction Approaches in Diabetes (GRADE) Cohort.
-
Lack of Association of Emotional Distress With Insulin Initiation in the GRADE Randomized Diabetes Comparative Effectiveness Trial.
-
Association of Hospitalizations With Randomized Glycemia-Lowering Treatment in GRADE.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication |
1.3; 1.3; 1.5; 0.8 | — |
| PRIMARY HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication |
852; 908; 860; 981 | — |
| SECONDARY Time to HbA1c>7.5%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication. |
2.1; 2.0; 2.2; 1.7 | — |
| SECONDARY HbA1c>7.5%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication. |
498; 633; 583; 697 | — |
Eligibility Criteria
Inclusion Criteria
- Men or women diagnosed with diabetes at age ≥ 30 years (≥ 20 for American Indians)
- Duration of diagnosed diabetes 3 times upper limit of normal
- Current alcoholism or excessive alcohol intake
- Previous organ transplant
- 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)
- Treatment with atypical antipsychotics
- 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
- Clinically or medically unstable with expected survival <1 year
- Unwillingness to permit sites to contact the PCP to communicate information about the study and the participant's data
- No non-study PCP or inability to identify such a PCP (who will provide non-study care) by the time of final run-in
- Participation in another interventional clinical trial
- Previous randomization in the GRADE study
- In the opinion of the principal investigator (PI), any other factor, including language barrier, likely to limit compliance with the protocol
Data sourced from ClinicalTrials.gov (NCT01794143) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.