Comparison of the Continuous Glucose Monitoring Profiles of Four Glucose-Lowering Medications in the GRADE Randomized Trial

Glycemic management metrics derived from continuous glucose monitoring (CGM) are increasingly recognized as important therapeutic targets. We performed one of the first comparisons of CGM metrics and achievement of CGM targets among four classes of glucose-lowering medications in combination with metformin. RESEARCH DESIGN AND METHODS The Glycemia Reduction Approaches in Diabetes (GRADE) study randomly assigned participants with type 2 diabetes and taking metformin to add one of four glucose-lowering medications (insulin glargine, glimepiride, liraglutide, or sitagliptin) and followed them for glycemic outcomes for 5 ± 1.3 years. A 2-week masked CGM analysis was conducted midstudy in 1,080 participants to evaluate CGM metrics, 24-h ambulatory glucose profile, and achievement of consensus goals. Treatment effects among the four groups were compared. RESULTS The sitagliptin and liraglutide groups had the highest time in range 70–180 mg/dL (TIR_70–180) and the lowest time below range <70 mg/dL (TBR_<70) and percentage coefficient of variation (%CV). The glimepiride group had the lowest TIR_70–180and the highest %CV, TBR_<70and number of CGM-derived hypoglycemic events (P < 0.001), and was the only drug showing daytime hypoglycemia. Sitagliptin and liraglutide were best for achieving consensus goals of very low TBR_<54<1% and the combined metric of TIR_70–180>70% and TBR_<70<4% (P < 0.001). When stratified by HbA1c, mean glucose did not differ among treatments, but %CV and TBR_<70were higher with glargine and glimepiride within each HbA1c stratum. CONCLUSIONS 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 HbA_1cto guide diabetes management.