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. 2024 Apr 1;47(4):610-619.
doi: 10.2337/dc23-2459.

Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)

Jeffrey S Gonzalez  1   2   3   4 , Ionut Bebu  5 , Heidi Krause-Steinrauf  5 , Claire J Hoogendoorn  1   2 , Gladys Crespo-Ramos  1   2 , Caroline Presley  6 , Aanand D Naik  7 , Shihchen Kuo  8 , Mary L Johnson  9 , Deborah Wexler  10 , Jill P Crandall  2 , Anne E Bantle  11 , Valerie Arends  12 , Andrea L Cherrington  13 ; GRADE Research Group
Collaborators, Affiliations

Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)

Jeffrey S Gonzalez et al. Diabetes Care. .

Abstract

Objective: We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments.

Research design and methods: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of <10 years' duration, HbA1c 6.8-8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined differences at 1 year and over the 3-year follow-up.

Results: Across treatments, diabetes distress (-0.24, P < 0.0001) and depressive symptoms (-0.67, P < 0.0001) decreased over 1 year. Diabetes distress was lower at 1 year for the glargine group than for the other groups combined (-0.10, P = 0.002). Diabetes distress was also lower for liraglutide than for glimepiride or sitagliptin (-0.10, P = 0.008). Over the 3-year follow-up, there were no significant group differences in total diabetes distress; interpersonal diabetes distress remained lower for those assigned to liraglutide. No significant differences were observed for depressive symptoms.

Conclusions: Contrary to expectations, this randomized trial found no evidence for a deleterious effect of basal insulin on emotional distress. Glargine lowered diabetes distress modestly at 1 year rather than increasing it. Liraglutide also reduced diabetes distress at 1 year. Results can inform treatment decisions for adults with early T2DM.

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Conflict of interest statement

Duality of Interest. J.S.G. reports consulting fees from Virta Health, payment or honoraria for a virtual presentation in Sāo Paulo, Brazil, in 2020, from the Worldwide Initiative for Diabetes Education, support for travel from the ADA Professional Conference Planning Committee, participation in a data monitoring committee for Vanderbilt University investigator Lindsay Mayberry, and receipt of Abbott Freestyle Libre devices outside the submitted work. C.J.H. reports grants from the National Institute on Aging, NIDDK, and JDRF outside the submitted work. G.C.-R. reports grants from JDRF and support for travel from the Let’s Empower and Prepare (LEAP) program (funded by ADA) outside the submitted work. C.P. reports grants from the National Center for Complementary and Integrative Health and ADA outside the submitted work. A.D.N. reports grants from the Center for Innovations in Quality, Effectiveness, and Safety outside the submitted work. M.L.J. reports grants for HealthPartners Institute from Sanofi, Lilly, and Novo Nordisk outside the submitted work. D.W. reports serving on data monitoring committees for Novo Nordisk, including the Effect of Semaglutide Versus Placebo on the Progression of Renal Impairment in Subjects With Type 2 Diabetes and Chronic Kidney Disease (FLOW) and Semaglutide Cardiovascular Outcomes (SOUL) trials, outside the submitted work. A.E.B. reports grants from the National Institutes of Health and support for travel from the ADA. A.E.B. serves on two data safety and monitoring boards for the University of Minnesota outside the submitted work. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
CONSORT (Consolidated Standards of Reporting Trials) diagram for EDS substudy to GRADE. Shown is the assignment of participants to the four treatment groups and completion of EDS.
Figure 2
Figure 2
Longitudinal diabetes distress and depressive symptoms profiles (mean and 95% confidence limits) by GRADE treatment group. PHQ-8, eight-item Patient Health Questionnaire. A: Longitudinal diabetes distress profiles. B: Longitudinal depressive symptoms profiles.
See this image and copyright information in PMC

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