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

Authors

• Richard M. Bergenstal, International Diabetes Center, HealthPartners Institute, Minneapolis, MN.
• Jill P. Crandall, Division of Endocrinology and Fleischer Institute for Diabetes & Metabolism, Albert Einstein College of Medicine, Bronx, NY.
• Samuel P. Rosin, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Bethesda, MD.
• Nicole M. Butera, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Bethesda, MD.
• Anne Bantle, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Minnesota, Minneapolis, MN.
• Cyrus Desouza, Division of Diabetes, Endocrinology & Metabolism, University of Nebraska Medical Center, Omaha Veterans Affairs Medical Center, Omaha, NE.
• Elizabeth Duran-Valdez, University of New Mexico, Albuquerque, NM.
• Stephanie Hall, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Bethesda, MD.
• William H. Herman, Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
• Mary L. Johnson, International Diabetes Center, HealthPartners Institute, Minneapolis, MN.
• Violet Lagari, Miami Veterans Affairs Healthcare System/University of Miami, Miami, FL.
• Mary E. Larkin, Diabetes Center, Massachusetts General Hospital, Harvard Medical School, Boston MA.
• Lawrence S. Phillips, Atlanta Veterans Affairs Medical Center, Decatur, GA.
• Holly J. Willis, International Diabetes Center, HealthPartners Institute, Minneapolis, MN.
• Heidi Krause-Steinrauf, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Bethesda, MD.

Document Type

Journal Article

Publication Date

4-2-2026

Journal

Diabetes care

DOI

10.2337/dc25-3055

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.

APA Citation

Bergenstal, Richard M.; Crandall, Jill P.; Rosin, Samuel P.; Butera, Nicole M.; Bantle, Anne; Desouza, Cyrus; Duran-Valdez, Elizabeth; Hall, Stephanie; Herman, William H.; Johnson, Mary L.; Lagari, Violet; Larkin, Mary E.; Phillips, Lawrence S.; Willis, Holly J.; and Krause-Steinrauf, Heidi, "Comparison of the Continuous Glucose Monitoring Profiles of Four Glucose-Lowering Medications in the GRADE Randomized Trial" (2026). GW Authored Works. Paper 9128.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/9128

Department

Biostatistics and Bioinformatics