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

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 mg/dL (TBR<70) and percentage coefficient of variation (%CV). The glimepiride group had the lowest TIR70-180, and the highest %CV, TBR<70, and 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 TIR70-180 >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.

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Journal
Diabetes Care
Published
2026-04-02
DOI
https://doi.org/10.2337/dc25-3055
Primary Topic
Diabetes Treatment and Management
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article
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article

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

C.R. Thacker, A. Bantle, M.N. Feinglos, Violet S. Lagari et al.
Diabetes Care
Diabetes Treatment and Management
article

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

C.R. Thacker, A. Bantle, M.N. Feinglos, Violet S. Lagari, Stephanie V. Hall, J.P. Crandall, K. Evans Kreider, J. English Jones, Samuel P. Rosin, Holly Willis, Larry Phillips, Cyrus Desouza, Elizabeth Duran-Valdez, R.P. Zimmer, Mary L. Johnson, Heidi Krause-Steinrauf, B.M. Satterwhite, N. Butera, S.A. Khan, J.B. Kimpel, P. Wilson, Jill P. Crandall, R. Chatterjee, P. Kringas, M. Rhee, M.D. McKee, L. Holloway, L. Savoye, E. Gonzalez Hattery, S. Person, R. Gaba, L. Alfano, E. Burgess, A. Kirpitch, S. Duran, L. Tucker, C.A. White, S. Gonzalez de la Torre, C. Sanders, H. AbouAssi, S. Tanukonda, A. Ideozu, H. Schneier, H. Estrella, C. Adams, R. Goland, L. Estrada, F. Ismail-Beigi, C. Gullett, L. Colosimo, A. Maxwell, T. Kulow, A. Werner, J. Boers, M.V. Kononets, R. Mungara, B. Cramer, C. Newman, K. Chionh, T.S. Raines, M. Sibymon, C. Wright, M. Maher-Albertelli, G. Montes, J. Lukin, C. Falck-Ytter, F. Morehead, M. Furst, J. Iacoboni, G. McPhee, C.N. Mariash, J. Brown-Friday, William H. Herman, P. Hollander, A. Smiley, C. Patel, K. Gumpel, D. Olson, Richard M. Bergenstal, A. Sood, J. Pring, A. Krol, J. Jimenez, A. Jackson, Mary E. Larkin, J.B. Green, K. Ballentine-Cargill, P. Burt, A. Balasubramanyam, L. Sayyed Kassem, J. Costello, C. Hausheer, E. Roe, S. Behringer-Massera, K.A. Stancil, E. Xhori, M. Tiktin, A. Ross, J. Tejada
article en

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 mg/dL (TBR<70) and percentage coefficient of variation (%CV). The glimepiride group had the lowest TIR70-180, and the highest %CV, TBR<70, and 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 TIR70-180 >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.

Diabetes Care
Albert Einstein College of Medicine (US), University of Minnesota (US), Milken Institute (US), Emory University (US), University of New Mexico (US), University of Michigan (US), Veterans Health Administration (US), Massachusetts General Hospital (US), Omaha VA Medical Center (US), Michigan Medicine (US), Department of Veterans Affairs (AU), Miami VA Healthcare System (US), HealthPartners (US)
American Diabetes Association, Centers for Disease Control and Prevention, National Heart, Lung, and Blood Institute, Division of Diabetes, Endocrinology, and Metabolic Diseases
Good health and well-being
Openalex Percentile: Top 29%
Diabetes Treatment and Management
DOISourceOpenAlex
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