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

Bergenstal RM, Crandall JP, Rosin SP, Butera NM, Bantle A, Desouza C, Duran-Valdez E, Hall S et al.

Diabetes care, 2026

1,080 participants · 1 citation

Abstract

Objective: 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 (TIR70-180) and the lowest time below range 70% and TBR<70 <4% (P < 0.001). When stratified by HbA1c, mean glucose did not differ among treatments, but %CV and TBR<70 were 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 HbA1c, to guide diabetes management.

How strong is the evidence?

Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 1,080 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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