Trial results for the GRADE Study (NCT01794143), a comparative effectiveness study of glycemia-lowering medications for Type 2 Diabetes, were posted on ClinicalTrials.gov on 2026-02-10. Among the treatments, liraglutide showed a median time of 1.5 years to HbA1c>=7%, which was longer than sitagliptin's 0.8 years in patients also receiving metformin.
Background
The GRADE Study (NCT01794143) investigated the comparative effectiveness of major glycemia-lowering medications for the treatment of Type 2 Diabetes. The study aimed to compare commonly used diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and patient-centered outcomes. Liraglutide is a GLP-1 receptor agonist included in this comparison.
Trial design
The GRADE Study (NCT01794143) was a Phase 3, pragmatic, unmasked clinical trial that enrolled 7850 participants with Type 2 Diabetes. The study compared the effectiveness of several glycemia-lowering medications when combined with metformin. The intervention arms included glimepiride (a sulfonylurea), sitagliptin (a DPP-4 inhibitor), liraglutide (a GLP-1 receptor agonist), and glargine insulin.
Key results
The trial results provided median times to specific HbA1c thresholds while participants received metformin and their assigned glucose-lowering study medication.
- For the outcome "Time to HbA1c>=7%":
- Liraglutide showed a median time of 1.5 years.
- Glargine Insulin U-100 and Glimepiride both showed a median time of 1.3 years.
- Sitagliptin showed a median time of 0.8 years.
- For the outcome "Time to HbA1c>7.5%":
- Liraglutide showed a median time of 2.2 years.
- Glargine Insulin U-100 showed a median time of 2.1 years.
- Glimepiride showed a median time of 2.0 years.
- Sitagliptin showed a median time of 1.7 years.
The number of participants who reached an HbA1c>=7% while on metformin and the assigned study medication were:
- Sitagliptin: 981 Participants
- Glimepiride: 908 Participants
- Liraglutide: 860 Participants
- Glargine Insulin U-100: 852 Participants
What this means
The results from the GRADE Study indicate that among the tested medications combined with metformin, liraglutide demonstrated a longer median time to reaching or exceeding an HbA1c of 7% and 7.5% compared to sitagliptin, glimepiride, and glargine insulin for the 7% threshold, and compared to sitagliptin and glimepiride for the 7.5% threshold. This suggests that liraglutide may offer more sustained glycemic control in some patients with Type 2 Diabetes when added to metformin, particularly when compared to sitagliptin in preventing HbA1c from rising above 7%.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT01794143, titled "A Comparative Effectiveness Study of Major Glycemia-lowering Medications for Treatment of Type 2 Diabetes," were posted on 2026-02-10 on clinicaltrials.gov.