Phase 3
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
Bottom Line
View on ClinicalTrials.gov: NCT01794143 ↗Enrolled (actual)
5,047
Serious AEs
8.2%
Results posted
Feb 2026
Primary outcome: Primary: Time to HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication — 1.3; 1.3; 1.5; 0.8 years
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sulfonylurea (glimepiride) (Drug); DPP-4 inhibitor (sitagliptin) (Drug); GLP-1 receptor agonist (liraglutide) (Drug); Insulin (glargine) (Drug)
- Age
- Adult, Older Adult · 30+ yrs
- Sex
- All
- Sponsor
- GRADE Study Group
- Primary completion
- Apr 2021
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 | — |
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.
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). 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.