American Diabetes Association
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Impact of Glucose-Lowering Medications on Health-Related Quality of Life in the Glycemia Reduction Approaches in Diabetes (GRADE) Study: A Comparative Effectiveness Randomized Clinical Trial

posted on 2024-01-08, 21:13 authored by Andrea L. Cherrington, Mark T. Tripputi, Naji Younes, William H. Herman, Aimee Katona, Erik J. Groessl, Jacqueline Craig, Jeffrey S. Gonzalez, Rajesh Garg, Sabina Casula, Shihchen Kuo, Hermes J. Florez

Objective: Diabetes is associated with reduced health-related quality of life (HRQoL). Information on the relationship between HRQoL and glucose-lowering medications in recently diagnosed type 2 diabetes (T2D) is limited. We assessed changes in HRQoL in participants with T2D receiving metformin plus one of four glucose-lowering medications in the GRADE study.

Research Design and Methods: 5047 participants with baseline mean age of 57 years, <10 years T2D duration, glycated hemoglobin level of 6.8–8.5%, taking metformin monotherapy were randomly assigned to glargine, glimepiride, liraglutide, or sitagliptin. HRQoL was evaluated at baseline in 4885 participants, and at years 1, 2, and 3 (Y1-Y3), using the Quality of Well-Being Self-Administered Scale (QWB-SA) and the 36-Item Short-Form Health Survey physical and mental component summary scales (PCS, MCS). Linear models analyzed changes in HRQoL over time in intention-to-treat analyses.

Results: None of the medications worsened HRQoL. There were no differences in QWB-SA or MCS by treatment group at any time point. PCS scores improved with liraglutide versus other groups at Y1 only. Greater weight loss during Y1 explained half the improvement in PCS scores with liraglutide versus glargine and glimepiride. Liraglutide participants in the upper tertile of baseline body mass index showed the greatest improvement in PCS scores at Y1.

Conclusion: Adding liraglutide to metformin in participants within 10 years of T2D diagnosis showed improvement in the SF-36 PCS compared with the other medications at 1 year, which was no longer significant at Y2 and Y3. Improvement was related to weight loss and baseline BMI.


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 DK020541-44, P30 DK020572, P30 DK072476, P30 DK079626, P30 DK092926, P30 DK111022, U54 GM104940, UL1 TR000439, UL1 TR000445, UL1 TR001108, UL1 TR001409, UL1 TR001449, UL1 TR002243, UL1 TR002345, UL1 TR002378, UL1 TR002489, UL1 TR002529, UL1 TR002535, UL1 TR002537, and UL1 TR002548. Educational materials were provided by the National Diabetes Education Program. Material support in the form of donated medications and supplies were provided by Becton, Dickinson and Company, Bristol-Myers Squibb, Merck, NovoNordisk, 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.


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