Comparison of the Continuous Glucose Monitoring Profiles of Four Glucose-Lowering Medications in the Glycemia Reduction Approaches in Diabetes (GRADE) Randomized Trial
Authors' conclusion
Incretin class drugs had the lowest %CV, the least hypoglycemia, and best achievement of CGM-based glycemic targets. CGM metrics and profiles provide clinical insights, beyond HbA1c, to guide diabetes management.
Study context
- Population
- Participants with T2D taking metformin in the GRADE study, followed 5 ± 1.3 years; masked continuous glucose monitoring (CGM) midstudymasked CGM substudy
- Participants
- 1,080 participants
- Comparison
- Insulin glargine vs glimepiride vs liraglutide vs sitagliptin, added to metformin
Methodological details4-arm, 2-week masked CGM substudy (midstudy)
- 4-arm
- 2-week masked CGM substudy (midstudy)
Primary result
As reported in the abstract
CGM metrics (TIR70-180, TBR<70, %CV, hypoglycemic events) · midstudy
- Sitagliptin and liraglutide had the highest TIR70-180 and the lowest TBR<70 and %CV
- Glimepiride had the lowest TIR70-180 and the highest %CV, TBR<70 and number of CGM-derived hypoglycemic events
- Glimepiride was the only drug showing daytime hypoglycemia
- Between Glargine and Glimepiride: P < 0.001
Further findings
| Outcome | P value |
|---|---|
| Achievement of consensus CGM goals: TBR<54 <1%; combined TIR70-180 >70% and TBR<70 <4%Between Sitagliptin and Liraglutide | P < 0.001 |
- Achievement of consensus CGM goals: TBR<54 <1%; combined TIR70-180 >70% and TBR<70 <4%: comparison among the four groups (also Glargine, Glimepiride)
Achievement of consensus CGM goals: TBR<54 <1%; combined TIR70-180 >70% and TBR<70 <4%
- Sitagliptin and liraglutide were best for achieving consensus goals
CGM metrics stratified by HbA1c
- Mean glucose did not differ among treatments
- %CV and TBR<70 higher with glargine and glimepiride within each HbA1c stratum
Safety
- Glimepiride had the highest TBR<70 and number of CGM-derived hypoglycemic events and was the only drug showing daytime hypoglycemia
Original publication
Comparison of the Continuous Glucose Monitoring Profiles of Four Glucose-Lowering Medications in the GRADE Randomized Trial. Diabetes Care. Published 2 April 2026. doi:10.
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