Adults with type 2 diabetes mellitus (T2DM) receiving incretin-based therapies showed lower hypoglycemia and glycemic variability than those receiving glimepiride or insulin glargine. These findings were reported from a continuous glucose monitoring (CGM) substudy of the Glycemia Reduction Approaches in Diabetes (GRADE) trial published in Diabetes Care.

The analysis included adults with T2DM receiving metformin who were randomly assigned to insulin glargine, glimepiride, liraglutide, or sitagliptin. Participants were followed for glycemic outcomes for a mean of 5 years, and a 2-week masked CGM assessment was performed midway through the study in 1,080 participants. 

Findings

• Sitagliptin and liraglutide showed the highest time in range (TIR 70-180 mg/dL), while glimepiride showed the lowest TIR (P < 0.001).
• Sitagliptin and liraglutide also had the lowest time below range (TBR <70 mg/dL), whereas glimepiride had the highest TBR (P < 0.001).
• Glimepiride was the only treatment associated with daytime hypoglycemia on ambulatory glucose profiles.
• Glycemic variability (% coefficient of variation) was lowest with liraglutide and sitagliptin and highest with glimepiride (P < 0.001).
• Sitagliptin and liraglutide were most likely to achieve consensus CGM targets, including TBR <54 mg/dL below 1% and combined TIR >70% with TBR <4% (P < 0.001).
• Across HbA1c strata, mean glucose levels were similar among treatment groups, although glycemic variability and TBR remained higher with insulin glargine and glimepiride.

Liraglutide and sitagliptin were associated with lower glycemic variability, less hypoglycemia, and greater achievement of CGM-based glycemic targets than glimepiride or insulin glargine when added to metformin in adults with T2DM.