Comparative Effects of Randomized Second-line Therapy for Type 2 Diabetes on a Composite Outcome Incorporating Glycemic Control, Body Weight, and Hypoglycemia: An Analysis of Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)

Authors

M Sue Kirkman, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Mark Tripputi, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Heidi Krause-Steinrauf, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Ionut Bebu, The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Hiba AbouAssi, Duke University Medical Center, Durham, NC.
Henry Burch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Rockville, MD.
Elizabeth Duran-Valdez, University of New Mexico, Albuquerque, NM.
Hermes Florez, Department of Medicine, University of Miami, Miami, FL.
W Timothy Garvey, University of Alabama at Birmingham, Birmingham, AL.
Daniel S. Hsia, Pennington Biomedical Research Center, Baton Rouge, LA.
Maamoun Salam, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO.
Rodica Pop-Busui, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI.

Document Type

Journal Article

Publication Date

1-9-2024

Journal

Diabetes care

DOI

10.2337/dc23-1332

Abstract

OBJECTIVE: In Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) (5,047 participants, mean follow-up 5.0 years), differences in glycemic control were demonstrated over time among four randomized therapies added to metformin. Weight gain and hypoglycemia are also important outcomes for people with type 2 diabetes. We compared the effects of the four randomized GRADE medications on a composite outcome incorporating glycemic deterioration, weight gain, and hypoglycemia. RESEARCH DESIGN AND METHODS: The composite outcome was time to first occurrence of any of the following: HbA1c >7.5%, confirmed; ≥5% weight gain; or severe or recurrent nonsevere hypoglycemia. Secondary analyses included examination of individual components of the composite outcome, subgroup effects and potential mediators, and treatment satisfaction. Cumulative incidence was estimated with the Kaplan-Meier estimator. Cox proportional hazards models were used to assess pairwise group differences in risk of an outcome. RESULTS: Risk of reaching the composite outcome (events per 100 participants per treatment year [PTYs]) was lowest with liraglutide (19 per 100 PTYs) followed by sitagliptin (26 per 100 PTYs), glargine (29 per 100 PTYs), and glimepiride (40 per 100 PTYs); all pairwise comparisons were statistically significant. The order was the same for risk of weight gain and hypoglycemia, but risk of glycemic deterioration was lowest with glargine, followed by liraglutide, glimepiride, and sitagliptin. No significant heterogeneity in risk of composite outcome was detected across prespecified covariates. Participants who reached the composite outcome had modestly but significantly lower treatment satisfaction. CONCLUSIONS: Among participants treated with common second-line drug classes for type 2 diabetes, the liraglutide group had the lowest and glimepiride the highest risk of reaching a composite outcome encompassing glycemic deterioration, weight gain, and hypoglycemia. These findings may inform decision-making regarding type 2 diabetes therapy.

APA Citation

Kirkman, M Sue; Tripputi, Mark; Krause-Steinrauf, Heidi; Bebu, Ionut; AbouAssi, Hiba; Burch, Henry; Duran-Valdez, Elizabeth; Florez, Hermes; Garvey, W Timothy; Hsia, Daniel S.; Salam, Maamoun; and Pop-Busui, Rodica, "Comparative Effects of Randomized Second-line Therapy for Type 2 Diabetes on a Composite Outcome Incorporating Glycemic Control, Body Weight, and Hypoglycemia: An Analysis of Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)" (2024). GW Authored Works. Paper 4193.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4193

Department

Biostatistics and Bioinformatics