American Diabetes Association
Use_of_Rescue_Insulin_Supplement_07.12.23_clean.pdf (562.36 kB)

The Use of Rescue Insulin in the Glycemia Reduction Approaches in Diabetes (GRADE) Study

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posted on 2023-11-29, 20:22 authored by Priscilla A Hollander, Heidi Krause-Steinrauf, Nicole M. Butera, Erin J. Kazemi, Andrew J. Ahmann, Basma N Fattaleh, Mary L. Johnson, Tina Killean, Violet S Lagari, Mary E. Larkin, Elizabeth A Legowski, Neda Rasouli, Holly J Willis, Catherine L. Martin


To describe rescue insulin use and associated factors in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study.


GRADE participants (type 2 diabetes <10 years, baseline A1C 6.8% to 8.5% on metformin monotherapy, N=5,047) were randomly assigned to insulin glargine U-100, glimepiride, liraglutide, or sitagliptin and followed quarterly for a mean of 5 years. Rescue insulin (glargine or aspart) was to be started within 6 weeks of A1C >7.5%, confirmed. Reasons for delaying rescue insulin were reported by staff-completed survey.


Nearly one-half of GRADE participants (N=2,387, 47.3%) met the threshold for rescue insulin. Among participants assigned to glimepiride, liraglutide, or sitagliptin, rescue glargine was added by 69% (39% within 6 weeks). Rescue aspart was added by 44% of glargine-assigned participants (19% within 6 weeks), and by 30% of non-glargine assigned participants (14% within 6 weeks). Higher A1C values were associated with adding rescue insulin. Intention to change health behaviors (diet/lifestyle, adherence to current treatment) and not wanting to take insulin were among the most common reasons reported for not adding rescue insulin within 6 weeks.


Proportionately, rescue glargine, when required, was more often used than rescue aspart, and higher A1C values were associated with greater rescue insulin use. Wanting to use non-insulin strategies to improve glycemia was commonly reported, although multiple factors likely contributed to not using rescue insulin. These findings highlight the persistent challenge of intensifying type 2 diabetes treatment with insulin, even in a clinical trial.


The GRADE Study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health under Award Number U01DK098246. The planning of GRADE was supported by a U34 planning grant from the NIDDK (U34-DK-088043). The American Diabetes Association supported the initial planning meeting for the U34 proposal. The National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention also provided funding support. The Department of Veterans Affairs provided resources and facilities. Additional support was provided by grant numbers P30 DK017047, P30 DK020541, P30 DK020572, P30 DK072476, P30 DK079626, P30 DK092926, U54 GM104940, UL1 TR000170, UL1 TR000439, UL1 TR000445, UL1 TR001102, UL1 TR001108, UL1 TR001409, 2UL1TR001425, UL1 TR001449, UL1 TR002243, UL1 TR002345, UL1 TR002378, UL1 TR002489, UL1 TR002529, UL1 TR002535, UL1 TR002537, UL1 TR002541 and UL1 TR002548. Educational materials have been provided by the National Diabetes Education Program. Material support in the form of donated medications and supplies has been provided by Becton, Dickinson and Company, Bristol-Myers Squibb, Merck & Co., Inc., Novo Nordisk, Roche Diagnostics, and Sanofi. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The GRADE Study Research Group is deeply grateful to our participants whose loyal dedication made GRADE possible.


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